INVESTIGATIONS OPERATIONS MANUAL 2023 CHAPTER 5

5-1 

CHAPTER 5 - ESTABLISHMENT INSPECTIONS 

CONTENTS

CHAPTER 5 - ESTABLISHMENT INSPECTIONS................... 5-1

SUBCHAPTER 5.1 - INSPECTION INFORMATION ............... 5-5

5.1.1 - AUTHORITY TO ENTER AND INSPECT..................... 5-5

5.1.1.1 - FDA Investigator's Responsibility............................... 5-5

5.1.1.2 - Credentials................................................................. 5-5

5.1.1.3 - Written Notice ............................................................ 5-5

5.1.1.4 - Written Observations ................................................. 5-5

5.1.1.5 - Receipts..................................................................... 5-5

5.1.1.6 - Written Demand for Records ..................................... 5-5

5.1.1.7 - Written Requests for Information ............................... 5-5

5.1.1.7.1 – LACF / AF Food Inspections .................................. 5-5

5.1.1.7.2 – Requests for Records under Section 703 of the 

FD&C Act................................................................................. 5-6

5.1.1.8 - Business Premises .................................................... 5-6

5.1.1.9 - Premises Used for Living Quarters ............................ 5-6

5.1.1.10 - Facilities where Electronic Products are Used or Held

................................................................................................. 5-6

5.1.1.11 - Multiple Occupancy Inspections............................... 5-6

5.1.1.12 - Authority for Examinations and Investigations ......... 5-6

5.1.1.13 - Authority to Implement Section 702(e)(5) of the FD&C 

Act ............................................................................................ 5-6

5.1.1.13.1 - SCOPE ................................................................. 5-7

5.1.1.13.2 - INSPECTIONAL GUIDANCE................................ 5-7

5.1.1.13.3 - FOLLOW UP GUIDANCE..................................... 5-7

5.1.1.13.4 - SEARCH WARRANTS ......................................... 5-7

5.1.1.14 - Products Imported Under the Provisions of Section 

801(d)(3) of the FD&C Act ....................................................... 5-7

5.1.1.14.1 - REQUIREMENTS FOR BIOTERRORISM ACT.... 5-7

5.1.1.14.2 - INSPECTIONAL PREPARATION......................... 5-8

5.1.2 - INSPECTIONAL APPROACH ...................................... 5-8

5.1.2.1 - Depth of Inspection.................................................... 5-8

5.1.2.2 - Inspection Walk Through ........................................... 5-8

5.1.2.3 - Signing Non-FDA Documents.................................... 5-9

5.1.2.4 - Technical Assistance ................................................. 5-9

5.1.2.5 - Team Inspections....................................................... 5-9

5.1.2.5.1 - TEAM MEMBER RESPONSIBILITIES ................... 5-9

5.1.2.5.2 - TEAM LEADER RESPONSIBILITIES..................... 5-9

5.1.2.6 - Post-Inspectional Contacts ...................................... 5-10

5.1.3 - INSPECTION OF FOREIGN FIRMS........................... 5-10

5.1.3.1 – Review of Foreign-Language Document................. 5-10

5.1.4 - INSPECTIONAL PRECAUTIONS............................... 5-10

5.1.4.1 - Clothing.................................................................... 5-11

5.1.4.2 - PHS Recommendations - Basic Sanitary Practices . 5-11

5.1.4.3 - Representatives Invited by the Firm to View the 

Inspection............................................................................... 5-11

5.1.5 - GENERAL PROCEDURES & TECHNIQUES............. 5-12

5.1.5.1 - Candling................................................................... 5-12

5.1.5.2 - Label Review ........................................................... 5-12

5.1.5.3 - Field Exams ............................................................. 5-12

SUBCHAPTER 5.2 - INSPECTION PROCEDURES ............. 5-12

5.2.1 - PRE-INSPECTIONAL ACTIVITIES............................. 5-12

5.2.1.1 - Pre-Announcements ................................................ 5-13

5.2.1.1.1 - BASIC PREMISES................................................ 5-13

5.2.1.1.2 - CRITERIA FOR CONSIDERATION...................... 5-14

5.2.1.1.3 - PROCEDURES..................................................... 5-14

5.2.1.2 - Personal Safety ....................................................... 5-14

5.2.1.2.1 - PREPARATION .................................................... 5-14

5.2.1.2.2 - PHYSICAL RESISTANCE/THREATS/ ASSAULTS.. 5-

15

5.2.1.3 – eNSpect Personal Safety Alert................................ 5-16

5.2.1.4 – Personal Safety Plan............................................... 5-16

5.2.2 - NOTICE OF INSPECTION ......................................... 5-17

5.2.2.1 - Multiple Date Inspections......................................... 5-17

5.2.2.2 - Inspection of Vehicles ............................................. 5-18

5.2.2.3 - Follow-Up Inspections by Court Order .................... 5-18

5.2.2.4 - Conducting Regulatory Inspections When the Agency is 

Contemplating Taking, or is Taking, Criminal Action............. 5-18

5.2.2.5 - When Evidence of a Criminal Violation is Discovered in 

the Course of a Regulatory Inspection .................................. 5-19

5.2.2.6 - Use of Evidence Gathered in the Course of a Criminal 

Investigation .......................................................................... 5-19

5.2.2.7 - Use of Evidence Voluntarily Provided to the Agency5-20

5.2.2.8 - Concurrent Administrative, Civil, and Criminal Actions 5-

20

5.2.2.9 - Working with a Grand Jury ...................................... 5-20

5.2.3 - REPORTS OF OBSERVATIONS............................... 5-20

5.2.3.1 - Preparation of Form FDA 483, FDA 483a, and FDA 

4056 ...................................................................................... 5-21

5.2.3.1.1 - INDIVIDUAL HEADINGS ..................................... 5-21

5.2.3.1.2 - SIGNATURE POLICY .......................................... 5-24

5.2.3.1.3 - DATE ISSUED ..................................................... 5-24

5.2.3.1.4 - OBSERVATIONS ................................................. 5-24

5.2.3.1.5 - MEDICAL DEVICE INSPECTIONS...................... 5-25

5.2.3.1.6 - CORRECTION OF FDA 483, FDA 483a, and FDA 

4056 ERRORS...................................................................... 5-25

5.2.3.1.6.1 - Errors Discovered Prior to Leaving the 

Establishment........................................................................ 5-25

5.2.3.1.6.2 - Errors Discovered after Leaving the Establishment5-

25

5.2.3.2 - Reportable Observations......................................... 5-26

5.2.3.2.1 – Adulteration Observations ................................... 5-26

5.2.3.2.2 - OTHER OBSERVATIONS ................................... 5-26

5.2.3.3 - Non-Reportable Observations................................. 5-27

5.2.3.4 - Annotation of the FDA 483 and FDA 4056.............. 5-28

5.2.3.5 - Government Wide Quality Assurance Program 

(GWQAP) .............................................................................. 5-28

5.2.3.6 - FDA 483, FDA 483a, and FDA 4056....................... 5-28

5.2.3.6.1 – Non-eNSpect generated FDA 483, FDA 483a, and 

FDA 4056 .............................................................................. 5-29

5.2.3.6.2 – eNSpect generated FDA 483, FDA 483a, and FDA 

4056 ...................................................................................... 5-29

5.2.4 - RECEIPT - FACTORY SAMPLES.............................. 5-29

5.2.4.1 - Items Requiring Receipt.......................................... 5-29

5.2.4.2 - Items Not Requiring Receipt ................................... 5-29

5.2.5 - INSPECTION REFUSAL............................................ 5-29

5.2.5.1 - Refusal to Permit Inspection ................................... 5-30

5.2.5.2 - Refusal to Permit Access to or Copying of Records 5-30

5.2.5.3 - Refusal after Serving Warrant ................................. 5-30

5.2.5.4 - Hostile and Uncooperative Interviewees ................. 5-30

5.2.5.4.1 - INDICATORS ....................................................... 5-31

5.2.5.4.2 - SAFETY PRECAUTIONS .................................... 5-31

5.2.5.4.3 - PROCEDURES WHEN THREATENED OR 

ASSAULTED ......................................................................... 5-31

5.2.5.4.4 - NOTIFICATION OF FBI AND US ATTORNEY..... 5-31

5.2.6 - INSPECTION WARRANT .......................................... 5-32

5.2.7 - DISCUSSIONS WITH MANAGEMENT...................... 5-32

5.2.7.1 - Protection of Privileged Information......................... 5-32

5.2.7.2 - Refusals of Requested Information ......................... 5-33

5.2.8 - CONSUMER COMPLAINTS...................................... 5-33

5.2.9 - INTERVIEWING CONFIDENTIAL INFORMANTS..... 5-33

5.2.9.1 - How to handle the first contact ................................ 5-33

5.2.9.1.1 - INTERVIEWING METHODS/TECHNIQUES........ 5-33

5.2.9.1.2 - ESTABLISH MOTIVATION .................................. 5-34

5.2.9.1.3 - ANONYMITY........................................................ 5-34

5.2.9.2 - Protect the Identity of the Source ............................ 5-34

5.2.9.2.1 - ACCESS .............................................................. 5-34

5.2.9.2.2 - STORAGE REQUIREMENTS.............................. 5-34

5.2.9.2.3 - DISCLOSURE...................................................... 5-34

5.2.9.2.4 - DESTRUCTION ................................................... 5-35
CHAPTER 5 INVESTIGATIONS OPERATIONS MANUAL 2023

5-2

5.2.10 - ROUTINE BIOSECURITY PROCEDURES FOR VISITS 

TO FACILITIES HOUSING OR TRANSPORTING DOMESTIC 

OR WILD ANIMALS...............................................................5-35

5.2.10.1 - Pre-Inspection Activities.........................................5-35

5.2.10.2 - General Inspection Procedures .............................5-36

5.2.10.3 - Special Situation Precautions ................................5-37

5.2.10.3 – Standard Operating Biosecurity Procedures for Egg 

Farm Inspections/ commercial Poultry Operations.................5-37

SUBCHAPTER 5.3 - EVIDENCE DEVELOPMENT...............5-40

5.3.1 - TECHNIQUES ............................................................5-40

5.3.2 -SAMPLES....................................................................5-40

5.3.3 - EXHIBITS ...................................................................5-40

5.3.4 - PHOTOGRAPHS........................................................5-41

5.3.4.1 - In-Firm Photographs ................................................5-41

5.3.4.2 - Photo Identification and Submission........................5-42

5.3.4.2.1 – FILM BASED PRINTS..........................................5-42

5.3.4.2.2 - COLOR SLIDE IDENTIFICATION ........................5-42

5.3.4.2.3 - NEGATIVE IDENTIFICATION ..............................5-42

5.3.4.2.4 - VIDEO RECORDINGS .........................................5-42

5.3.4.2.5 – DIGITAL PHOTOGRAPHS OR VIDEO 

RECORDINGS.......................................................................5-43

5.3.4.2.6 – GLOSSARY OF DIGITAL TERMINOLOGY.........5-43

5.3.4.2.6.1 – Digital Data .......................................................5-43

5.3.4.2.6.2 – Analog Data ......................................................5-43

5.3.4.2.6.3 – Memory Card ....................................................5-43

5.3.4.2.6.4 - Original ..............................................................5-43

5.3.4.2.6.5 – Original Copy ....................................................5-43

5.3.4.2.6.6 - Permanent Storage Media.................................5-43

5.3.4.2.6.7 - Time/Date Stamp...............................................5-44

5.3.4.2.6.8 - Working Copy ....................................................5-44

5.3.4.3 - Preparing and Maintaining Digital Photographs as 

Regulatory Evidence..............................................................5-44

5.3.4.4 - Preparing Digital Photos for Insertion in an eNSpect 

Establishment Inspection Report (EIR)..................................5-45

5.3.4.5 - Photograph Requests ..............................................5-45

5.3.5 - RECORDINGS ...........................................................5-45

5.3.6 - RESPONSIBLE INDIVIDUALS...................................5-46

5.3.6.1 - Discussion on Duty, Power, Responsibility ..............5-46

5.3.6.2 - Inspection Techniques How to Document Responsibility

...............................................................................................5-46

5.3.7 - GUARANTEES AND LABELING AGREEMENTS......5-47

5.3.7.1 - Guarantee................................................................5-47

5.3.7.2 - Labeling Agreement.................................................5-47

5.3.7.3 - Exemption Requirements.........................................5-47

5.3.8 - RECORDS OBTAINED...............................................5-47

5.3.8.1 - Verification of Source Records ................................5-48

5.3.8.2 - Identification of Records Collected...........................5-48

5.3.8.3.1 - ELECTRONIC RECORDS....................................5-48

5.3.8.3.1.1 ORIGINAL COPY.................................................5-49

5.3.8.3.1.2 WORKING COPY ................................................5-49

5.3.8.3.2 - ELECTRONIC DATABASES AND QUERIES.......5-49

5.3.8.3.2.1 - REQUESTING Electronic RECORDS from 

databases ..............................................................................5-50

5.3.8.3.2.2 - ELECTRONIC RECORDS RECEIVED VIA 

SECURE TRANSMISSION OR ON ELECTRONIC STORAGE 

MEDIA ...................................................................................5-50

5.3.8.3.3.1 - IDENTIFYING AND SECURING ELECTRONIC 

STORAGE MEDIA.................................................................5-51

5.3.8.5 - Listing of Records ....................................................5-51

5.3.8.6 - Patient and/or Consumer Identification on Records.5-51

5.3.9 - REQUEST FOR SAMPLE COLLECTION...................5-52

5.3.10 - POST-INSPECTION NOTIFICATION LETTERS......5-52

SUBCHAPTER 5.4 – FOOD AND COSMETICS INSPECTIONS

...............................................................................................5-52

5.4.1 - FOOD and COSMETIC INSPECTIONS .....................5-52

5.4.1.1 - Preparation and References ....................................5-52

5.4.1.2 - Inspectional Authority...............................................5-53

5.4.1.2.1 - WRITTEN DEMAND FOR RECORDS..................5-53

5.4.1.2.2 - WRITTEN REQUEST FOR INFORMATION ........ 5-53

5.4.1.3 - Records Access Under Sections 414 and 704 of the 

FD&C Act .............................................................................. 5-53

5.4.1.4 - Food and Cosmetic Defense Inspectional Activities 5-54

5.4.1.4.1 - FOOD AND COSMETIC SECURITY ................... 5-54

5.4.1.4.2 - RECONCILIATION EXAMINATIONS................... 5-55

5.4.1.4.3 - RECONCILIATION EXAMINATION GUIDANCE 

PART A ................................................................................. 5-55

5.4.1.4.4 - RECONCILIATION EXAMINATION GUIDANCE 

PART B ................................................................................. 5-55

5.4.1.4.5 - SPECIAL SAFETY PRECAUTIONS .................... 5-56

5.4.1.5 - Food Registration.................................................... 5-56

5.4.1.5.1 – FOOD FACILITY REGISTRATION EXEMPTIONS . 5-

57

5.4.1.5.2 - FOOD FACILITY REGISTRATION RESOURCES5-58

Beginning January 4, 2020, an owner, operator, or agent in 

charge of a facility must submit their registration to FDA 

electronically, unless FDA has granted a waiver under 21 CFR 

1.245 (see 21 CFR 1.231(a)(2)). If the firm needs to submit a 

waiver request, inform them that they may obtain a registration 

form to complete and submit by mail at 

http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms

/Forms/UCM071977.pdf. Also encourage the firm to submit the 

optional information on the registration form to assist and 

facilitate FDA’s future communications with the firm. ............ 5-58

5.4.2 - PERSONNEL ............................................................. 5-58

5.4.2.1 - Management ........................................................... 5-58

5.4.2.2 - Employees .............................................................. 5-58

5.4.3 - PLANTS AND GROUNDS ......................................... 5-59

5.4.3.1 - Plant Construction, Design and Maintenance ......... 5-59

5.4.3.2 - Waste Disposal ....................................................... 5-59

5.4.3.3 - Plant Services ......................................................... 5-60

5.4.4 - RAW MATERIALS...................................................... 5-60

5.4.4.1 - Handling Procedure................................................. 5-60

5.4.4.2 - Condition................................................................. 5-60

5.4.4.3 - Food Chemicals Codex ........................................... 5-60

5.4.5 - EQUIPMENT AND UTENSILS................................... 5-60

5.4.5.1 - Filtering Systems..................................................... 5-61

5.4.5.2 – Cleaning and Sanitization of Equipment and Utensils 5-

61

5.4.5.3 - Conveyor Belt Conditions........................................ 5-61

5.4.5.4 - Utensils ................................................................... 5-61

5.4.5.5 - Mercury and Glass Contamination .......................... 5-61

5.4.5.6 - UV Lamps ............................................................... 5-61

5.4.5.7 - Chlorine Solution Pipes ........................................... 5-61

5.4.5.8 - Sanitation Practices................................................. 5-61

5.4.6 - PROCESS AND CONTROLS .................................... 5-61

5.4.6.1 - Ingredient Handling ................................................. 5-62

5.4.6.2 - Formulas ................................................................. 5-62

5.4.6.3 - Food Additives......................................................... 5-62

5.4.6.4 - Color Additives ........................................................ 5-63

5.4.6.5 - Quality Control......................................................... 5-63

5.4.6.5.1 - INSPECTION SYSTEM........................................ 5-64

5.4.6.5.2 - LABORATORY TESTS ........................................ 5-64

5.4.6.5.3 - MANUFACTURING CODE SYSTEM................... 5-64

5.4.6.6 Packaging, Labeling, and Packing............................. 5-64

5.4.6.6.1 - QUANTITY OF CONTENTS................................. 5-64

5.4.6.6.2 - LABELING............................................................ 5-64

5.4.6.6.3 – NUTRITIONAL AND ALLERGEN LABELING...... 5-64

5.4.6.6.4 – SANITARY OPERATIONS.................................. 5-65

5.4.6.6.6 Labeling violations................................................ 5-65

5.4.6.6.7 Cosmetic product labeling making drug claims..... 5-65

5.4.7 - SANITATION.............................................................. 5-65

5.4.7.1 - Routes of Contamination......................................... 5-66

5.4.7.1.1 - INSECTS.............................................................. 5-66

5.4.7.1.2 - RODENTS............................................................ 5-66

5.4.7.1.3 - PESTICIDES........................................................ 5-66

5.4.7.1.4 - OTHER................................................................. 5-67
INVESTIGATIONS OPERATIONS MANUAL 2023 CHAPTER 5

5-3 

5.4.7.2 - Microbiological Concerns......................................... 5-67

5.4.7.2.1 - PROCESSING EQUIPMENT................................ 5-67

5.4.7.2.2 - EMPLOYEE PRACTICES..................................... 5-68

5.4.7.3 - Storage .................................................................... 5-68

5.4.7.3.1 - FOOD TRANSPORT VEHICLES.......................... 5-68

5.4.7.3.2 - VEHICLES AT RECEIVERS................................. 5-68

5.4.7.3.3 - VEHICLES AT SHIPPERS ................................... 5-68

5.4.8 - DISTRIBUTION .......................................................... 5-68

5.4.8.1 - Promotion and Advertising....................................... 5-69

5.4.8.2 - Recall Procedure ..................................................... 5-69

5.4.8.3 - Complaint Files ........................................................ 5-69

5.4.9 - OTHER GOVERNMENT INSPECTION...................... 5-69

5.4.9.1 - Federal..................................................................... 5-69

5.4.9.2 - State and Local........................................................ 5-69

5.4.9.3 - Grade A Dairy Plant Inspections.............................. 5-69

5.4.10 - FOOD STANDARDS ................................................ 5-70

5.4.10.1 - Food STANDARDS Inspection .............................. 5-70

5.4.10.2 - Food Inspection Report.......................................... 5-70

5.4.10.2.1 - ESTABLISHMENT INSPECTION RECORD (EI 

RECORD) .............................................................................. 5-70

5.4.10.2.2 - BODY OF REPORT............................................ 5-71

5.4.10.2.3 - SPECIAL INFORMATION SECTION.................. 5-71

5.4.10.3 - Violative Inspections .............................................. 5-71

5.4.12 - PESTICIDES ............................................................ 5-71

5.4.12.1 - Pesticide Inspections ............................................. 5-71

5.4.12.2 - Current Practices ................................................... 5-71

5.4.12.3 - Growers ................................................................. 5-72

5.4.12.3.1 - PESTICIDE APPLICATION ................................ 5-72

5.4.12.3.2 - PESTICIDE MISUSE/DRIFT/SOIL 

CONTAMINATION................................................................. 5-72

5.4.12.4 - Packers and Shippers............................................ 5-73

5.4.12.5 - Pesticide Suppliers ................................................ 5-73

5.4.12.6 - Pesticide Applicators.............................................. 5-73

5.4.12.7 - Sample Collections ................................................ 5-73

5.4.13 – COSMETIC INSPECTIONS..................................... 5-73

5.4.13.1 Preparation and References .................................... 5-73

5.4.13.2 – Documents and Records....................................... 5-74

5.4.13.3- Contaminated Cosmetics........................................ 5-74

5.4.13.4- Cosmetic Ingredients .............................................. 5-74

5.4.13.5 – Specific Types of Product Safety Concerns .......... 5-74

5.4.14 – Foreign Supplier Verification Program ..................... 5-75

SUBCHAPTER 5.5 - DRUGS ................................................ 5-75

5.5.1 - DRUG INSPECTIONS................................................ 5-75

5.5.1.1 - Preparation and References .................................... 5-75

5.5.1.2 - Inspectional Approach ............................................. 5-76

5.5.2 - DRUG REGISTRATION & LISTING........................... 5-76

5.5.3 - PROMOTION AND ADVERTISING............................ 5-77

5.5.4 - GUARANTEES AND LABELING AGREEMENTS...... 5-77

5.5.5 - OTHER INSPECTIONAL ISSUES.............................. 5-77

5.5.5.1 - Intended Use ........................................................... 5-77

5.5.5.2 - Drug Approval Status............................................... 5-77

5.5.5.3 – Drug Status Questions ............................................ 5-77

5.5.5.4 – Verification of Compliance with PDMA Requirements. 5-

77

5.5.5.5 - Drug/Dietary Supplement Status.............................. 5-77

5.5.5.6 - Approved Drugs....................................................... 5-77

5.5.5.7 - Investigational Drugs ............................................... 5-77

5.5.5.8 - Clinical Investigators and/or Clinical Pharmacologists . 5-

77

5.5.5.9 – Delaying, Denying, Limiting or Refusing Drug 

Inspections............................................................................. 5-77

5.5.8 - DRUG INSPECTION REPORT .................................. 5-78

SUBCHAPTER 5.6 - DEVICES .............................................. 5-78

5.6.1 - DEVICE INSPECTIONS ............................................. 5-78

5.6.1.1 - Technical Assistance ............................................... 5-78

5.6.1.2 - Sample Collection During Inspection ....................... 5-78

5.6.1.3 - Types of Inspections................................................ 5-79

5.6.2 - MEDICAL DEVICE QUALITY SYSTEM/ GOOD 

MANUFACTURING PRACTICES ......................................... 5-79

5.6.2.1 - Pre-Inspectional Activities ....................................... 5-79

5.6.2.2 - Quality Audit............................................................ 5-81

5.6.2.3 - Records................................................................... 5-81

5.6.2.4 - Complaint Files........................................................ 5-81

5.6.3 - STERILE DEVICES.................................................... 5-82

5.6.4 - LABELING .................................................................. 5-82

5.6.5 - GOVERNMENT-WIDE QUALITY ASSURANCE 

PROGRAM (GWQAP)........................................................... 5-82

5.6.6 - CONTRACT FACILITIES ........................................... 5-82

5.6.7 - SMALL MANUFACTURERS...................................... 5-82

5.6.8 - BANNED DEVICES.................................................... 5-83

5.6.9 – REPORTS OF CORRECTIONS AND REMOVALS .. 5-83

5.6.10 – TRACKED MEDICAL DEVICES.............................. 5-83

5.6.11 - DEVICE INSPECTION REPORTS........................... 5-83

5.6.12 – Medical Device and Electronic Radiation Product 

Controls (EPRC).................................................................... 5-83

5.6.12.1 – Electronic Product Radiation Controls (EPRC) 

Inspections ............................................................................ 5-83

5.6.12.1.1 – Inspection Authority for ERC Products .............. 5-83

5.6.12.1.2 – Pre-inspectional Activities for EPRC Inspections5-83

5.6.12.1.3 – Inspection of EPRC Facilities ............................ 5-84

SUBCHAPTER 5.7 - BIOLOGICS......................................... 5-84

5.7.1 - DEFINITION............................................................... 5-84

5.7.2 - BIOLOGICS INSPECTIONS ...................................... 5-84

5.7.2.1 - Authority .................................................................. 5-84

5.7.2.1.1 - BLOOD AND SOURCE PLASMA INSPECTIONS 5-85

5.7.2.1.2 – HUMAN TISSUE INSPECTIONS ........................ 5-85

5.7.2.2 – Donor Confidentiality .............................................. 5-85

5.7.2.3 – Inspectional Objectives........................................... 5-85

5.7.2.4 - Preparation.............................................................. 5-85

5.7.2.5 - Inspectional Approach............................................. 5-86

5.7.2.5.1 Access of Electronic Databases and Queries......... 5-86

5.7.2.6 - Regulations, Guidelines, Recommendations........... 5-86

5.7.2.7 - Technical Assistance............................................... 5-87

5.7.2.8 Biologics Establishment Inspection Reports............ 5-87

5.7.3 - REGISTRATION, LISTING AND LICENSING............ 5-87

5.7.3.1 - Registration and Listing........................................... 5-87

5.7.3.1.1 – TRANSFUSION SERVICES................................ 5-87

5.7.3.1.2 - HCT/PS................................................................ 5-87

5.7.3.1.3 - LABORATORIES ................................................. 5-87

5.7.3.1.4 - MILITARY BLOOD BANKS.................................. 5-87

5.7.3.2 – MOUs ..................................................................... 5-88

5.7.3.3 - Biologics License..................................................... 5-88

5.7.4 - TESTING LABORATORIES....................................... 5-88

5.7.5 - BROKERS .................................................................. 5-88

SUBCHAPTER 5.8 - TOBACCO PRODUCTS...................... 5-88

5.8.1 - DEFINITIONS ............................................................ 5-88

5.8.2 – TOBACCO INSPECTIONS ....................................... 5-89

5.8.3 - RETAIL COMPLIANCE CHECK INSPECTION 

CONTRACTS........................................................................ 5-89

5.8.4 - GUIDANCE, COMPLIANCE & REGULATORY 

INFORMATION ..................................................................... 5-89

SUBCHAPTER 5.9 - VETERINARY MEDICINE ................... 5-89

5.9.1 - CVM WEBSITE.......................................................... 5-89

5.9.2 - VETERINARY DRUG ACTIVITIES ............................ 5-89

5.9.3 - MEDICATED FEEDS AND TYPE A ARTICLES ........ 5-90

5.9.4 - BSE ACTIVITIES........................................................ 5-90

5.9.4.1 – Biosecurity Procedures for BSE Inspections at Poultry 

Facilities and Farms .............................................................. 5-90

5.9.5 - DRUG RESIDUES ..................................................... 5-91

5.9.6 - VETERINARY DEVICES............................................ 5-91

5.9.7 - ANIMAL GROOMING AIDS ....................................... 5-92

5.9.8 – PRODUCTS INTENDED FOR CONTROL OF FLEAS 

AND TICKS ........................................................................... 5-92

SUBCHAPTER 5.10 – BIORESEARCH MONITORING (BIMO) 5-

92
CHAPTER 5 INVESTIGATIONS OPERATIONS MANUAL 2023 

5-4 

5.10.1 – BIMO Establishment Type Definitions...................... 5-92

5.10.2 – BIMO Assignments .................................................. 5-93

5.10.2.1. READ-ONLY ACCESS TO ELECTRONIC 

DATABASES DURING BIORESEARCH MONITORING 

INSPECTION ASSIGNMENTS.............................................. 5-93

5.10.2.2 ELECTRONIC REGULATORY NOTES FOR BIMO 

OPERATIONS ....................................................................... 5-94

5.10.3 – BIMO Compliance Programs ................................... 5-94

5.10.4 – Postmarket Adverse Event Reporting ...................... 5-94

5.10.5 - Risk Evaluation and Mitigation Strategies (REMS)... 5-94

5.10.6 BIMO Establishment Inspection Reports (EIRs) ......... 5-94

5.10.7 BIMO Affidavits ........................................................... 5-95

5.10.8 BIMO Collection Reports (CRs) .................................. 5-95

5.10.8.1 Sample Type............................................................ 5-95

5.10.8.2 Sample Description.................................................. 5-95

5.10.8.3 Reason for Collection............................................... 5-95

5.10.8.4 Associated Firms...................................................... 5-96

5.10.8.5 Product Code and Product Name ............................ 5-96

5.10.8.6 Brand Name............................................................. 5-96

5.10.8.7 Product Label........................................................... 5-96

5.10.8.8 Sample Flags ........................................................... 5-96

5.10.8.9 Estimated Value....................................................... 5-96

5.10.8.10 CR & Records Sent To FACTS Org....................... 5-96

SUBCHAPTER 5.11 – REPORTING ..................................... 5-96

5.11.1 - ESTABLISHMENT INSPECTION REPORT (EIR) .... 5-97

5.11.2 – ENDORSEMENT ..................................................... 5-97

See Exhibit 5-14 for more information on profiling CGMP/QS 

Compliance Status................................................................. 5-97

5.11.2.1 – Reporting Verified Corrective Actions ................... 5-97

5.11.2.1.1 - REPORTING CRITERIA..................................... 5-98

5.11.2.1.2 - DATA ELEMENTS.............................................. 5-98

5.11.3 – eNSpect ESTABLISHMENT INSPECTION REPORT 

COVERSHEET ...................................................................... 5-98

5.11.3.1 – Inspection Basis.................................................... 5-98

5.11.4 - NARRATIVE REPORT ............................................. 5-99

5.11.4.1 – Summary of Findings report for NAI Inspections . 5-100

5.11.4.2 – Summary of Findings for VAI Inspection............. 5-100

5.11.4.3 - Individual Narrative Headings .............................. 5-100

5.11.4.3.1 - STANDARD NARRATIVE REPORT................. 5-100

5.11.4.3.2 - SUMMARY ....................................................... 5-102

5.11.4.3.3 - ADMINISTRATIVE DATA ................................. 5-102

5.11.4.3.4 - HISTORY.......................................................... 5-103

5.11.4.3.5 - INTERSTATE (I.S.) COMMERCE..................... 5-103

5.11.4.3.6 - JURISDICTION (PRODUCTS MANUFACTURED 

AND/OR DISTRIBUTED)..................................................... 5-103

5.11.4.3.7 - INDIVIDUAL RESPONSIBILITY AND PERSONS 

INTERVIEWED .................................................................... 5-104

5.11.4.3.8 - FIRM'S TRAINING PROGRAM ........................ 5-104

5.11.4.3.9 - MANUFACTURING/DESIGN OPERATIONS ... 5-104

5.11.4.3.10 - MANUFACTURING CODES........................... 5-105

5.11.4.3.11 - COMPLAINTS................................................. 5-105

5.11.4.3.12 - RECALL PROCEDURES................................ 5-105

5.11.4.3.13 - OBJECTIONABLE CONDITIONS AND 

MANAGEMENT'S RESPONSE ........................................... 5-105

5.11.4.3.13.1 - Supporting Evidence and Relevance........... 5-105

5.11.4.3.13.2 - Discussion with Management ...................... 5-105

5.11.4.3.14 - REFUSALS ..................................................... 5-105

5.11.4.3.15 - GENERAL DISCUSSION WITH MANAGEMENT . 5-

106

5.11.4.3.16 - ADDITIONAL INFORMATION ........................ 5-106

5.11.4.3.17 - SAMPLES COLLECTED ................................ 5-106

5.11.4.3.18 - VOLUNTARY CORRECTIONS....................... 5-106

5.11.4.3.19 - EXHIBITS COLLECTED................................. 5-107

5.11.4.3.20 – ATTACHMENTS ............................................ 5-107

5.11.4.3.21 - SIGNATURE................................................... 5-107

5.11.5 - EXHIBITS ............................................................... 5-107

5.11.5.1 - Electronic Records as Exhibits and Attachments . 5-108

5.11.6 ATTACHMENTS....................................................... 5-108

5.11.7 - Corrections to Endorsed Establishment Inspection 

Reports................................................................................ 5-108

SUBCHAPTER 5.12 – COMBINATION PRODUCTS.......... 5-108

5.12.1 – COMBINATION PRODUCT INSPECTIONS ......... 5-108

5.12.1.1 – Preparation......................................................... 5-109

5.12.1.2 – Inspectional Approach........................................ 5-109

5.12.1.3 – Registration and Listing...................................... 5-109

5.12.1.4 – Combination Product Establishment Inspection Report

............................................................................................ 5-109

5.12.1.5 – Limitations on Inspection.................................... 5-109

5-1 FORM FDA 482 NOTICE OF INSPECTION ................. 5-110

5-2 - FORM FDA 482a ........................................................ 5-113

5-3 FORM FDA 482b .......................................................... 5-114

5-5 FORM FDA 483 ............................................................ 5-115

5-6 INSERTING DIGITAL PHOTOS INTO eNSpect (RESIZE 

PHOTO) .............................................................................. 5-117

5-65-7 INSERTING DIGITAL PHOTOS INTO eNSpect (INSERT 

PHOTO) .............................................................................. 5-118

5-8 INSERTING DIGITAL PHOTOS INTO eNSpect (RESIZING 

USING MS OFFICE PICTURE MANAGER)........................ 5-119

5-9 FACTS CREATE SAMPLE ASSIGNMENT SCREEN... 5-120

5-10 FORM FDA 482c NOTICE OF INSPECTION – REQUEST 

FOR RECORDS.................................................................. 5-121

5-11 FOOD ADDITIVE NOMOGRAPH I.............................. 5-122

5-11 FOOD ADDITIVE NOMOGRAPH II............................. 5-123

5-12 SUMMARY OF REGISTRATION AND LISTING HUMAN 

PHARMACEUTICALS......................................................... 5-124

5-13 SUBSTANTIALLY EQUIVALENT MEDICAL DEVICES.... 5-

125

5-14 eNSpect PROFILE - COMSTAT ................................. 5-126

PROFILING A FIRM’S CGMP/QS COMPLIANCE STATUS 5-126

Table 5-14.1 Quick Reference Guide........................... 5-126

Table 5-14.2 Example of a Maintain Profiles screen.... 5-127

5-14.1 Introduction .................................................... 5-127

5-14.2 Purpose.......................................................... 5-127

5-14.3 Instructions..................................................... 5-127

5-14.3.1 Pre-Inspection Preparation ............................ 5-127

5-14.3.2 Firm’s Operations .......................................... 5-127

5-14.3.3 Maintain Profiles Screen................................ 5-127

5-14.3.4 Previous Inspection Profile ............................ 5-127

5-14.3.5 Firm Information ............................................ 5-127

5-14.3.6 Inspection Coverage of Profile Class Codes . 5-127

5-14.3.7 Discontinue and Delete Buttons .................... 5-128

5-14.3.8 CGMP Inspection and Other Toggle Buttons 5-128

5-14.3.9 Initial, In Review, and Final............................ 5-128

5-14.3.10 Final Profile Status ....................................... 5-128

5-14.3.10.1 Other Status ................................................. 5-128

5-14.3.10.2 Acceptable Status....................................... 5-128

5-14.3.10.3 Unacceptable Status ................................... 5-128

5-14.3.10.3.1 Continuation of Unacceptable Status ............ 5-128

5-14.3.10.3.2 Changing from Unacceptable to Acceptable Status

............................................................................................ 5-128

5-14.3.11 Remark Status Field....................................... 5-129

5-14.3.12 Remarks Field ................................................ 5-129

5-14.3.13 Out-of-Business Firm...................................... 5-129

5-14.3.14 Firm Merge ..................................................... 5-129

5-14.3.15 Troubleshooting.............................................. 5-129

5-14.4 Contact Information........................................ 5-129

5-14.5 Data Quality Assurance Projects.............................. 5-129

5-14.6 Establishment Profile Criteria......................... 5-130

Table 5-14.6.1 ..............Device, Biologic, Drug, and Veterinary 

Establishments TO Profile ................................................ 5-130

Table 5-14.6.2 ... Establishment and Operations NOT to Profile

......................................................................................... 5-130

5-14.6.3 Pre-Approval Inspections ............................... 5-131

5-14.7 Profile Classes and Codes............................. 5-131

5-14.7.1 Profile Class Codes ........................................ 5-131

Table 5-14.7.1.1 Biologics ............................................... 5-131
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Table 5-14.7.1.2 Devices ................................................. 5-131

Table 5-14.7.1.3 Drugs and Veterinary ............................ 5-132

Table 5-14.7.1.4 Special Veterinary................................. 5-133

5-15 COMPLIANCE ACHIEVEMENT REPORT .................. 5-134

5-16 FACTS REIMBURSABLE CHECK BOX...................... 5-135

5-17 FORM FDA 4056 - PRODUCE FARM INSPECTION 

OBSERVATIONS .............................................................. 5-136

5-18 – FORM FDA 483a ...................................................... 5-145

SUBCHAPTER 5.1 - INSPECTION 

INFORMATION

5.1.1 - AUTHORITY TO ENTER AND INSPECT

See IOM 2.2 for discussion of statutory authority.

It is your obligation to fulfill the following requirements because failure to do so may prevent use of evidence and 

information obtained during the inspection.

There may be occasions where you may be accompanied 

on your inspection or investigation by other officials. These 

officials may be state or local officials who have their own 

inspectional authority or other officials who do not have 

authority to enter the firm. You should obtain permission 

from the firm’s most responsible person if officials without 

inspection authority wish to accompany you during your 

inspection/investigation. You should document in your EIR 

when other non-FDA officials accompany you during your 

inspection, and whether they entered under their own 

authority or the responsible individual at the firm gave 

permission (identify, by name and title, the responsible 

individual giving permission). See IOM 5.2.2 and 

5.11.4.3.3. 

5.1.1.1 - FDA Investigator's Responsibility

Your authority to enter and inspect establishments is 

predicated upon specific obligations to the firm as described below. It is your responsibility to conduct all inspections at reasonable times and within reasonable limits 

and in a reasonable manner. Proceed with diplomacy, tact 

and persuasiveness.

During inspections or investigations, when you have 

evidence of conditions whereby there is a reasonable 

probability the associated products will cause imminent and 

serious adverse health consequences or death, you should 

notify your supervisor immediately to consider a Risk 

Control Review (RCR) evaluation. 

5.1.1.2 - Credentials

Display your credentials to the top management official be 

it the owner, operator, or agent in charge. See IOM 5.2.2.

NOTE: Although management may examine your credentials and record the number and your name, do not permit 

your credentials to be photocopied. Federal Law (Title 18, 

U.S.C. 701) prohibits photographing, counterfeiting, or 

misuse of official credentials. Do not permit a firm to take 

your fingerprints, contact your SCSO for more information. 

5.1.1.3 - Written Notice

After showing the firm's representative your credentials, 

issue the original, properly executed, and signed FDA 482, 

Notice of Inspection, to the top management official (full 

name). Keep a copy for submission with your report. A 

notice of inspection is not required to be issued during 

foreign inspections; however, credentials should be 

presented to the top management official. An example of a 

properly executed FDA 482 can be found at Exhibit 5-1.

5.1.1.4 - Written Observations

Upon completing the inspection and before leaving the 

premises, provide the highest management official available your inspectional findings on an FDA 483 - Inspectional Observations or an FDA 4056, Produce Farm 

Inspection Observations, for produce safety inspections. 

See Section 704(b) of the FD&C Act [21 U.S.C. 374 (b)] 

and IOM 5.2.3 and 5.2.7.

5.1.1.5 - Receipts

Upon completion of the inspection, furnish the top 

management official the original of the FDA-484 - Receipt 

for Samples describing any samples obtained during the 

inspection. See IOM 5.2.4.

5.1.1.6 - Written Demand for Records

In low-acid canned food and acidified food EI's, an FDA 

482a - Demand for Records (exhibit 5-2) is required under 

21 CFR 108.35(h) and 21 CFR 108.25(g) to obtain records 

required by 21 CFR 113 and 114.

5.1.1.7 - Written Requests for Information

There are several methods of requesting records. These 

may include a request for information under LACF or AF 

inspections, and FDA 482d Request for FSVP Records,703 

written requests, and requests for records under the BT Act

(IOM 5.4.1.3).

5.1.1.7.1 – LACF / AF Food Inspections

In low-acid canned foods and acidified foods EI's, an FDA 

482b, Request for Information (exhibit 5-3), is required 

under 21 CFR 108.35(c)(3)(ii) and 21 CFR 108.25(c)(3)(ii)

to obtain information concerning processes and procedures 

required under 21 CFR 113 and 114. 
CHAPTER 5 INVESTIGATIONS OPERATIONS MANUAL 2023 

5-6 

5.1.1.7.2 – Requests for Records under

Section 703 of the FD&C Act

Per CPG Sec. 160.300, Requests for Records under 

Section 703 [21 U.S.C. 373], evidence obtained in 

response to a specific written request under Section 703 

cannot be used in a criminal prosecution of the person from 

whom obtained. With Supervisory approval, in certain 

circumstances, you may decide to issue a 703 written 

request when the importance of the evidence is crucial to 

protecting the public health. 

Procedure: All 703 written requests must comply with IOM 

4.4.4.2.2. Consider obtaining the evidence from other 

sources before using the 703 written request. In the case of 

foods and feeds, if there is a risk or threat of serious 

adverse health consequences, the division program

division should invoke the BT Act records access authority. 

All BT Act records requests must comply with IOM 5.4.1.3.

5.1.1.8 - Business Premises

Authority to inspect firms operating at a business location 

is described in IOM 5.1.1 and requires issuing 

management an FDA 482, Notice of Inspection, and 

presenting your credentials. A warrant for inspection is not 

necessary unless a refusal or partial refusal is encountered 

or anticipated.

5.1.1.9 - Premises Used for Living Quarters

All inspections where the premises are also used for living 

quarters must be conducted with a warrant for inspection 

unless:

Owner Agreeable - The owner or operator is fully agreeable and offers no resistance or objection whatsoever. 

Cleary document in the EIR that you are inspecting a 

residence and the owner was agreeable. or;

Physically Separated - The actual business operations to 

be inspected are physically separated from the living 

quarters by doors or other building construction. These 

would provide a distinct division of the premises into two 

physical areas, one for living quarters and the other for 

business operations, and you do not enter the living area.

In both the latter cases, proceed as any other inspection 

with the appropriate presentation of credentials and issuance of a Notice of Inspection. For safety precautions, it is 

recommended that two credentialed FDA employees are 

present when conducting inspections in a residence.

5.1.1.10 - Facilities where Electronic 

Products are Used or Held

Section 537(a) of the FD&C Act provides the FDA with the 

authority to inspect the facilities of manufacturers in certain 

circumstances. The electronic product radiation control 

provisions were originally enacted as the Radiation Control 

for Health and Safety Act of 1968 (P.L. 90-602)

It is lawful for FDA personnel to enter the facilities of an 

electronic product distributor, dealer, assembler or user for 

the purpose of testing an electronic product for radiation 

safety when the entry is voluntarily permitted. Congress has 

not specifically prohibited FDA from conducting such 

voluntary examinations and such examinations would 

clearly agree with the congressional declaration of purpose 

expressed in section 532(a) of the RCH&S Act.

Under the Medical Device Authority, electronic products 

utilized in human and/or veterinary medicine, e.g., x-ray, 

laser, ultra-sound, diathermy, etc. can be considered prescription devices. In these cases the authority of Section 

704 of the FD&C Act [21 U.S.C. 374] can be used to obtain 

entry to inspect the user facility. If the Medical Device 

Authority is utilized, credentials must be displayed and a 

FDA 482, Notice of Inspection, must be issued.

5.1.1.11 - Multiple Occupancy Inspections

You are required per FD&C Act 704(a)(1) [21 U.S.C. 

374(a)(1)] to issue a Notice of Inspection, FDA 482, to each 

firm inspected. When firms have operations located in 

different sites or buildings, you should use judgment to 

determine when multiple FDA 482 forms need to be issued. 

For sites located a distance apart, it is preferable to issue a 

FDA 482 to the most responsible person at each site. One 

rule of thumb which can be used is if the sites or buildings 

are within walking distance, your original Notice of 

Inspection can be considered sufficient to cover both. 

During your initial interview with management, after you 

issue the FDA 482, make sure you clearly indicate the 

facility and sites you intend to inspect. The Act requires the 

issuance of a Notice of Inspection, but does not prohibit 

issuing multiple notices if management so requests. As with 

all of our work, good judgment, and knowledge of the OEI 

and the FD&C Act are necessary in deciding what legally 

must be done.

5.1.1.12 - Authority for Examinations and

Investigations

Section 702(a) of the FD&C Act [21 U.S.C. 372 (a)] authorizes examinations and investigations for the purpose of 

enforcing the Act.

5.1.1.13 - Authority to Implement Section 

702(e)(5) of the FD&C Act

Section 702(e) of the FD&C Act [21 U.S.C. 372 (e)] contains certain authorities relating to counterfeit drugs including the authority to seize ("confiscate") counterfeit 

drugs and containers, counterfeiting equipment, and all 

other items used or designed for use in making counterfeit 

drugs prior to the initiation of libel proceedings. This authority has been delegated, with certain restrictions, to 

holders of official credentials consistent with their authority 

to conduct enforcement activities. Additional authority in 

702(e) to make arrests, to execute and serve arrest warrants, to carry firearms, or to execute seizure by process 
INVESTIGATIONS OPERATIONS MANUAL 2023 CHAPTER 5

5-7 

under Section 304 of the FD&C Act [21 U.S.C. 334] have 

not been delegated. 

The agency does intend to utilize the authority contained 

in Section 702(e) to execute and serve search warrants, 

but such use does not require delegation from the ACRA.

Section 702(e)(5) contains authority for such delegated 

persons to confiscate all items which are, or which the 

investigator has reasonable grounds to believe are, subject 

to seizure under Section 304(a)(2). Items subject to 

seizure, and thus to confiscation under Section 702(e)(5), 

includes most things associated with counterfeit drugs. 

Confiscation authority does not, however, extend to vehicles, records, or items (i.e., the profits) obtained as a result 

of counterfeiting.

5.1.1.13.1 - SCOPE

Under this delegation, with supervisory concurrence and 

prior to the initiation of libel proceedings, investigators and 

inspectors are authorized to confiscate:

1. Any counterfeit drug, 

2. Any container used to hold a counterfeit drug,

3. Any raw material used in making a counterfeit drug, 

4. Any labeling used for counterfeit drug, 

5. Any equipment used to make a counterfeit drug including punches, dies, plates, stones, tableting machines, 

etc., 

6. Any other thing which you have reasonable grounds to 

believe is designed or used in making a counterfeit drug.

NOTE: You and your supervisor must be constantly aware 

of the potential dangers involved in confiscating property 

from individuals. Special care should be taken to ensure 

your safety. Arranging for teams of investigators to conduct 

the investigation, or arranging for assistance by local police, 

or other agencies with police powers, should be considered 

in planning the confiscation of counterfeit materials.

5.1.1.13.2 - INSPECTIONAL GUIDANCE

Guidance provided for implementing the authority to confiscate drug counterfeits is as follows:

1. The authority is not to be utilized unless there has been 

an agency determination the drug to be confiscated is a 

counterfeit and it is a drug which "without authorization, 

bears a trademark, *** or any likeness" of a legitimate 

product. The determination usually is based upon

evidence supplied by the firm whose product is being 

counterfeited. A written agency determination will issue 

to the Program Division Director from the Office of 

Enforcement and Import Operations (OEIO), in 

conjunction with the Center for Drug Evaluation and 

Research or the Center for Veterinary Medicine. 

2. When engaged in counterfeit investigations, you should 

proceed as follows upon encountering items to be 

confiscated.

a. Evaluate safety needs and check the location to ensure it is safe to proceed. Do not attempt to remove 

an item by force. If it appears there will be resistance, 

contact the local police, or other agencies with police 

powers for backup, if not already done in advance.

b. Inventory the items to be confiscated.

c. Prepare a written receipt and offer it to the person in 

charge.

d. Remove the items, if possible, from the premises (if 

they cannot be removed, secure them under seal).

e. Place all items removed under lock at a secure location. In most cases, confiscated items will be stored 

at the program division or resident post office until 

they are seized.

5.1.1.13.3 - FOLLOW UP GUIDANCE

After items are confiscated, certain actions must be taken 

to bring confiscated items under the control of the court. 

Proceed as follows:

1. After an item is confiscated, immediately notify your 

supervisor.

2. Supervisors must then notify the appropriate compliance units of the items confiscated.

3. Compliance units should initiate seizure proceedings 

against any items confiscated.

4. Office of Medical Products and Tobacco Program 

Operations (OMPTO) should be advised of any action 

utilizing this authority.

5.1.1.13.4 - SEARCH WARRANTS

Section 702(e)(2) contains authority to execute and serve 

search warrants. Proceed as instructed by your program 

division after a search warrant has been obtained.

5.1.1.14 - Products Imported Under the 

Provisions of Section 801(d)(3) of the FD&C 

Act

The FDA Export Reform and Enhancement Act of 1996 (PL 

104-134 and 104-180) amended the FD&C Act by adding 

Section 801(d)(3) [21 U.S.C. 381 (d)(3)] ("Import for 

Export") which permits the importation of unapproved drug 

and medical device components, food additives, color 

additives, and dietary supplements intended for further 

incorporation or processing into products destined for 

export from the United States. Section 801(d)(3) [21 U.S.C. 

381 (d)(3)] was subsequently amended by Section 322 of 

the Public Health Security and Bioterrorism Preparedness 

and Response Act of 2002 (Bioterrorism Act), Public Law 

107-188, which specified certain requirements an importer 

has to satisfy in order to import a product under this Section.

See IOM 6.2.3.4.

5.1.1.14.1 - REQUIREMENTS FOR 

BIOTERRORISM ACT

These requirements include:

1. A statement confirming the intent to further process 

such article or incorporate such article into a product to 
CHAPTER 5 INVESTIGATIONS OPERATIONS MANUAL 2023 

5-8 

be exported,

2. The identification of all entities in the chain of possession of the imported article,

3. A certificate of analysis "as necessary to identify the 

article" (unless the article is a device), and

4. Executing a good and sufficient bond providing for 

liquidated damages in the event of default, in 

accordance with U.S. Customs. 

In addition, the initial owner or consignee must keep records showing the use of the imported articles and must be 

able to provide upon request a report showing the disposition or export of the imported articles. An article imported under this section, and not incorporated or further 

processed, must be destroyed or exported by the owner or 

consignee. Failure to keep records or to make them available to FDA, making false statements in such records, 

failure to export or destroy imported articles not further 

incorporated into finished products, and introduction of the 

imported article or final product into domestic commerce 

are Prohibited Acts under Section 301(w).

Filers making entry under the Import for Export provisions 

must identify entry/line submissions with the intended use 

code Import for Export and Affirmation of Compliance 

"IFE" (Import for Export), and supply FDA with written 

documentation stating the product is entered under the 

Import for Export provisions. A Certificate of Analysis (as 

necessary) and identification of all involved entities must 

be submitted in writing to the import program division. The 

import program division will ensure all written documentation has been uploaded to the entry/line. The Office 

of Import Operations (OIO) will make IFE entry information 

and documentation available to the home program division 

of the initial owner or consignee through the “Import for 

Export Entry Lines and Documents Past 2 Years“ report 

located at http://oradss.fda.gov:8085/reports/ora/diop/ife/

5.1.1.14.2 - INSPECTIONAL PREPARATION

Before conducting an Establishment Inspection, refer to 

IOM Sections 6.2.3.4.2 and 6.2.3.4.3 for instructions on 

obtaining the “Import for Export Entry Lines and 

Documents Past 2 Years” report and the follow-up 

activities required for IFE entry/lines. 

5.1.2 - INSPECTIONAL APPROACH

An establishment inspection is a careful, critical, official 

examination of a facility to determine its compliance with 

the laws and regulations administered by FDA. Inspections 

may be used to collect evidence to document violations and 

to support regulatory action, when appropriate, or they may 

be directed to obtaining specific information on new 

technologies, good commercial practices, or data for 

establishing food standards or other regulations. In order to 

facilitate on-the-job training, multiple points of view, and 

perspectives of firms being inspected whenever practical, 

those with assignment authority, should consider assigning 

different Investigator/s or different Lead Investigators at 

different times. This is recommended particularly when 

there have been multiple sequential NAI inspections or 

when the firm's management has been uncooperative.

The approach and scope (e.g. full scope, limited scope; 

Level I, II or III; and full or abbreviated) used to conduct an

inspection is defined by the compliance program, 

assignment, and/or your supervisor.

The inspectional approach used is according to the 

following definitions:

Comprehensive Inspection -directs coverage to everything 

in the firm subject to FDA jurisdiction to determine the firm’s 

compliance status; or

Directed Inspection -directs coverage to specific areas to 

the depth described in the program, assignment, or as 

instructed by your supervisor.

See IOM Chapter S for information on safety, use of 

protective gear, trash disposal, dealing with potential 

hazards and other safety issues.

See special report requirements in IOM Subchapter 1.7.3 

when objectionable conditions which may be of public 

health significance implicate establishments in other 

division(s).

5.1.2.1 - Depth of Inspection

The degree and depth of attention given various operations 

in a firm depends upon information desired, or upon the 

violations suspected or likely to be encountered. In 

determining the amount of attention to be given in specific 

cases, consider the: 

1. Current Compliance Program,

2. Nature of the assignment,

3. General knowledge of the industry and its problems,

4. Firm history, and

5. Conditions found as the inspection progresses.

5.1.2.2 - Inspection Walk Through

A walk-through inspection of the premises should be 

conducted as early as possible to become familiar with the 

operation and to plan the inspection strategy. A walkthrough visual inspection of the manufacturing site is helpful 

in establishing the depth of the inspection, learning about 

products and processes, identifying sources of 

manufacturing records and identifying potential areas of 

concern. The size of the facility, the number of employees, 

employee practices, environmental conditions inside and 

outside the plant, raw materials, manual and automated 

processes, sources of contamination, manufacturing flow, 

method of data collection including computer terminals, are 

some of the areas to be taken into consideration in 

establishing the depth of the inspection. A visual inspection 
INVESTIGATIONS OPERATIONS MANUAL 2023 CHAPTER 5

5-9 

of a manufacturing site should also be used to check 

obvious potential problem areas such as: general housekeeping, state of operation for processes and processing 

equipment, and people dependent operations. Visual inspections of areas used for failure investigation, product 

sampling and testing, product reworks, return goods, and 

product quarantine areas should be inspected for obvious 

potential product problems.

Depending on the product being inspected, some of the 

general inspectional equipment an investigator should have 

available, may include, eye and ear protection, boots and 

protective clothing. Some specialized equipment may 

include radiation or ethylene oxide (EO) monitoring 

devices, magnifiers, and timing devices as needed. For 

some domestic and foreign plant sites, investigators may 

be required to be inoculated prior to the inspection for 

protection from potential environmental concerns such as 

hepatitis, yellow fever, malaria and live biological products 

which may be encountered in vaccine products. See 

Chapter S. 

5.1.2.3 - Signing Non-FDA Documents

Occasionally a firm will request you sign various documents 

including:

1. A waiver which will exempt the firm from any responsibility or liability should an accident occur, and you are 

injured on the firm's premises,

2. Form letters concerning access to confidential information the firm does not want released,

3. A training form acknowledging that you were briefed on 

the personnel gowning procedures,

4. Information/data you request during the inspection be 

put into writing, etc.

If you receive such a request, inform the firm you are not 

authorized to sign such documents, letters, requests, 

waivers, etc., but will report the firm's request in your EIR. 

All FDA employees are authorized to sign-in and sign-out 

at a firm and to comply with security measures employed 

by the firm, including documenting the removal/replacement of seals to inspect vehicles and containers. See IOM 4.3.3.3 and 4.7.4.6. Obviously, the key 

issue is you are not authorized to waive, without supervisory approval, any of FDA's rights to inspect, sample, 

photograph, copy, etc. or to sign any interstate shipping 

record document which could infer the firm could not be 

prosecuted under the Act.

5.1.2.4 - Technical Assistance

If you determine specialized technical assistance is necessary in conducting inspections of new technologies, 

products or manufacturing procedures, it may be available 

through Regulatory Technical Assistance Network (rTAN), 

Produce Safety Network, Programmatic or National 

experts, other ORA components or Center scientists and 

engineers. If specialized skills are necessary and are not 

available locally or through your Division, contact the 

Division of Domestic Human and Animal Food Operations 

(DDHAFO) for CFSAN and CVM (food) products or Office 

of Medical Products and Tobacco Program Operations 

(OMPTO) for CBER, CDER, CDRH, CTP and CVM medical

products. See FMD-142 and IOM 1.9.2.2.1 for additional 

information.

5.1.2.5 - Team Inspections

The use of teams to conduct inspections may be beneficial. 

Very often individuals well versed in an analytical or 

inspectional technique or technology can provide assistance and advice. For combination product inspections, 

teams may be needed to bring appropriate program 

expertise to the inspection.(See IOM 5.12.1)

When inspection teams are involved in an inspection, one 

investigator will be designated as the team leader by the 

inspecting Division or by DDHAFO or OMPTO if a 

headquarters directed special inspection is involved. The 

team leader is in charge of the inspection and bears the 

overall responsibility for the inspection and the EIR. A team 

may consist of multiple investigators, laboratory personnel 

and other FDA employees, and your supervisor/coach, who 

may participate as part of the ORA Quality Assurance 

program.

5.1.2.5.1 - TEAM MEMBER 

RESPONSIBILITIES

Each team member is responsible for preparing those 

portions of the report pertaining to his/her activities. Team 

members shall identify their portion of the report, so they 

can later identify that portion as the part he/she performed 

and reported. Since reports should be written in the first 

person, one system might be to head each portion with a 

statement "The following operation(s) was/were observed 

and reported by Investigator ___________", who can then 

report in the first person.

All team members must sign the EIR or Produce Farm 

Inspection Report (PFIR), as applicable. Only those team 

members present at issuance sign the FDA 483, FDA 483a,

or FDA 4056. The issuance of the FDA 483 or FDA 483a

should not be delayed, in the absence of a team member's 

signature. See IOM 5.2.3.1.2 for instructions for signing an 

FDA 4056 and a multipage FDA 483.

5.1.2.5.2 - TEAM LEADER RESPONSIBILITIES

The Team Leader shall be responsible for:

1. Issuing unused notebooks for taking regulatory notes 

during the EI or investigation to headquarters personnel 

on the team. He/she is also responsible for instructions 

on their use, if necessary, and when the report is 

finished, for obtaining the headquarters individual's 

signature on the original EIR and completed and 

properly identified regulatory notes and submitting them 

to the supervisor for filing. 

2. Directing the overall inspection to accomplish the objectives of the assignment including;
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a. Planning the inspection,

b. Scheduling and coordinating team members' pre-inspection preparations,

c. Determining, to the extent possible, the firm will be 

open and operating,

d. Calling to pre-announce an inspection if required

e. Planning for needs of visiting scientists if applicable. 

When the team leader is not familiar with all the 

processes or technology involved in the inspection, 

provide for primary coverage of selected areas by 

other team members,

f. Determining an orderly, efficient, and effective approach and sequence to be used and discussing the 

inspection plan with the team,

g. Modifying the inspection plan as necessary during 

the EI, to permit following leads, documenting evidence, etc.,

h. Setting team policy on how communications with the 

firm are to be handled,

i. Discussing personal conduct in dealing with headquarters personnel as necessary,

j. Assuring an early understanding by team members 

of their roles in note taking and reporting,

k. Assuring communications are open among team 

members, especially if the team is allowed to separate and work independently,

l. Reviewing inspection progress at least daily, discussing remaining objectives with the team members, and setting objectives for the following day,

m. Continually assessing the progress of the inspection 

to evaluate how the inspectional approach is working 

and to keep the division supervisor advised of the 

inspection's progress,

n. Providing guidance and direction to team members 

as necessary,

o. Advising each team member of reporting 

responsibilities and dates when drafts are to be 

provided,

p. Following up promptly on any delays or failures to 

report as required, and

q. Assisting the supervisor with further follow up, as indicated.

3. Making sure any person who joins the team after the 

inspection has started presents credentials and issues 

an FDA 482, Notice of Inspection to the firm prior to 

actually taking part in the EI;

4. Completing and/or correcting the computer-generated

coversheet;

5. Preparing the Summary of Findings;

6. Completing all headings of an administrative nature in 

the narrative report;

7. Compiling and submitting the complete final report; and

8. Resolving any disputes or differences of opinion among 

the team members, including items, which may be listed 

on the FDA 483 or FDA 4056. 

5.1.2.6 - Post-Inspectional Contacts

If the firm contacts the Investigator after the inspection 

regarding the inspection or follow-up, the Investigator 

should refer the request to his or her supervisor or to 

Compliance Branch if a regulatory action is contemplated. 

The Investigator should not respond to the firm regarding 

the adequacy of the firm’s response to inspectional 

observations or any follow-up planned.

After the inspection is concluded, if the Investigator finds 

that a document or other required information is missing, 

the Investigator should discuss the needed information and 

how to proceed with their supervisor.

5.1.3 - INSPECTION OF FOREIGN FIRMS

Inspectional requirements apply to all inspections, including 

foreign inspections. However, there are some exceptions. 

For instance, the FDA 482 is not issued, unless the firm is 

a U.S. Military facility. Be guided by relevant Compliance 

Programs, assignments, and the Guide to International 

Inspections and HHS Travel Manual for other differences. 

5.1.3.1 – Review of Foreign-Language 

Document

When reviewing documents in a foreign language, do not 

use any web and mobile applications translation tools that 

have not been authorized by FDA for this particular 

purpose. Use of these tools may result in unauthorized 

disclosure of non-public information.

If, based on the information you are reviewing, you are 

confident that manually entering a single word or short 

phrase into an electronic tool for translation could not 

possibly jeopardize trade secrets or confidential 

information, you may do so. Ensure that, if all your 

searches were read together, the combination of searches 

would not result in any unauthorized disclosure.”

5.1.4 - INSPECTIONAL PRECAUTIONS

Our concern over microbiological contamination emphasizes the need for you to be alert to criticism or allegations 

that you may have contributed to or caused contamination 

at a firm. This is especially important in drug firms and highrisk food firms, among others. You must adhere to good 

sanitation practices to refute any such criticisms. You could 

also unknowingly introduce or spread disease during 

inspections of or visits to animal production or sale facilities, 

conducting environmental investigations at poultry layer 

facilities, conducting dairy farm inspections or audits of 

state activities, investigating drug residue reports or 

working in the veterinary bioresearch area or conducting 

produce safety inspections. See IOM 5.2.10 for information 

outlining precautions for you to follow.

Exercise caution in all activities in the firm. Follow the firm's 

sanitation program for employees and wash and sanitize 

hands, shoes, vehicles and equipment as indicated. 

Restrict unnecessary movement between various areas in 

plants and when possible, complete your activities in one 

area before moving to the next.
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When inspecting areas where sterility is maintained, or 

sterile rooms are located (especially in pharmaceutical or 

device firms), follow the sterile program required of the 

firm's employees. In general, it is unnecessary to enter 

sterile rooms except in the most extraordinary circumstances. These areas are usually constructed to provide 

visual monitoring. Take no unsterile items with you (notebook, pencils, etc.). In this type of situation, you can enter 

your observations in your regulatory notes immediately 

after leaving the sterile area.

Always use aseptic techniques, including hand sanitizing, 

when collecting in-line and raw material samples, as well 

as finished product samples for microbiological examination. See IOM 4.3.5. 

Do not use or consume a firm's products at any of a firm's 

facilities. This could be interpreted as accepting a product 

as being satisfactory and could possibly embarrass you and 

the Agency, both during the inspection and in the future. In 

general, consuming food products in a manufacturing area 

is considered an objectionable practice.

When conducting inspections of firm's using chemicals, 

pesticides, etc., ask to review the Material Safety Data 

Sheets (MSDS) for the products involved to determine 

what, if any, safety precautions you must take. This could 

include the use of respirators or other safety equipment.

5.1.4.1 - Clothing

Wear clean coveralls or other protective clothing for each 

inspection and if circumstances dictate, use a clean pair 

when returning from lunch, or upon entering certain machinery or critical areas.

Remove all jewelry and secure pens, pencils,, etc., so they 

cannot fall into the product or machinery. Do not depend on 

clips on pens, etc., to hold these items in your outer 

pockets.

Clean protective clothing should be either individually 

wrapped or placed in clean plastic bags and taped to protect from contamination. If the package has been sterilized, 

protect the package from possible contamination or 

puncture. The package should not be opened until you are 

ready to use the clothing. After use, clothing should be 

turned inside out as it is removed, and immediately placed 

in clean paper or plastic bags to prevent spread of contamination until washed and/or sterilized.

Use disposable hair and head coverings throughout the 

inspection and disposable hand and foot coverings in areas 

where floor tracking or cross contamination may be a factor. 

Use hard hats and other protective devices where the 

situation dictates.

If reusable protective boots are used, wash and sanitize 

before each use. Always use sterile disposable boot covers 

when entering machinery such as dryers or where unavoidable contact with product is a factor.

When discarding contaminated disposable head and boot 

coverings, it is suggested they be placed with used clothing 

for proper disposal after leaving the plant area.

See IOM 5.2.10.1 for protective clothing and equipment 

necessary when visiting livestock or poultry producing 

areas.

5.1.4.2 - PHS Recommendations - Basic 

Sanitary Practices

FDA personnel are not required by law to have health certificates, take physical exams or submit to requirements, 

which ensures their compliance with sanitary procedures 

in the performance of their official duties. However, it is 

critical you adhere to basic sanitation practices. See S.8.1 

- General Preventive and Protective Measures and 

https://fda.sharepoint.com/sites/insideFDAEmployeeResources/SitePages/Occupational-HealthServices.aspx,S.17.2 - Immunizations, and S.17.3 - 

Physical Examinations.

The Food Code 2017 is available electronically from the 

FDA CFSAN web page under Federal/State ProgramsRetail Food Safety References. Printed copies may be 

ordered from the National Technical Information Service

website.

5.1.4.3 - Representatives Invited by the Firm 

to View the Inspection

While conducting an inspection, you may find the firm's 

management has invited individuals who are not directly 

employed by the firm to view the inspectional process (e.g., 

representatives from the press, trade associations, 

consumer groups, congressional staff, other company officials).

Regardless of whom the firm invites to observe the progress of an inspection, the presence of outside representatives should not disrupt the inspectional process. You 

should continue to conduct the inspection in a reasonable 

fashion. The presence of these individuals should have no 

impact on the manner in which the inspection progresses 

except you should take precautions to preserve the 

confidentially of any information you may have obtained as 

a result of the Agency's statutory authority. This is 

especially true when the inspection is recorded via 

videotaping, other photography, and/or audio recordings. 

Where applicable, refer to IOM 5.3.5 for procedures on how 

to prepare your own recording in parallel with the firm's 

recording.

It is the Agency's position that while the investigator must 

protect privileged information provided to him/her during the 

inspection, it is the firm's responsibility to protect 

privileged/confidential information observed or recorded by 

those individuals invited by the firm.
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5.1.5 - GENERAL PROCEDURES & 

TECHNIQUES

The procedures and techniques applicable to specific inspections and investigations for foods, drugs, devices,

tobacco products, cosmetics, radiological health, or other 

FDA operations are found in part in the IOM (inspectional 

and investigational policy/procedure), and the Compliance 

Program Guidance Manual (program specific instructions). 

Some procedures and techniques which may be applicable 

to overlapping areas or operations are as follows:

5.1.5.1 - Candling

Candling is defined as: "to examine by holding between the 

eye and a light, especially to test eggs in this way for 

staleness, blood clots, fertility and growth." Like most 

techniques learned through the food inspection programs, 

there are uses for this technique in other program areas 

such as looking for mold in bottled liquids which could be 

drugs, devices or biologics. Candling can also be useful in 

the examination of original documents to see below whiteout or to look for over-writing.

Many types of products lend themselves to inspection by 

some type of candling. For these products, firms generally 

have candling equipment which may be built into the production lines or may be a separate operation.

Where checking products by candling, it may be possible to 

utilize the firm's candling equipment. Various other light 

sources for candling are also available including overhead 

projectors. Exercise care when using overhead projectors 

and protect the glass surface and the lens from scratches 

and damage. All candling is best accomplished when light 

outside the item being candled is masked so the light 

passes through the object rather than being diffused around 

it. A heavy paper or cardboard template can be quickly 

prepared at the time candling is done.

5.1.5.2 - Label Review

Do not undertake a critical review of labels unless instructed by the assignment, program, or your supervisor. 

Limit your comments to the mandatory label requirements 

required by the Acts. However, if after review of the formula, 

it is obvious an active ingredient or an otherwise mandatory 

ingredient statement does not appear on the label, such 

discrepancy may be called to management's attention. See 

also IOM 5.2.3.2 regarding labeling for blood and blood 

products.

If asked for other label comments, refer the firm to the appropriate Center to obtain a label review.

When the labeling is suspect or when you are requested to 

collect labels/labeling, collect a copyof all labels and 

accompanying literature for further review. For medical 

devices, if there is a question regarding the need for a new 

510(k) or PMA supplement, it is essential the label and 

labeling be collected.

5.1.5.3 - Field Exams

A field examination is an on-site examination of a domestic 

product (or a foreign product in domestic channels of trade) 

sufficient in itself to determine if the product is in

compliance with the Acts enforced by FDA. A field exam 

can be conducted of any commodity in any location. It is 

important to conduct field examinations during food 

inspections to detect violations, e.g., undeclared sulfiting 

agents, Certified color additives and allergens. If the 

examination does not reveal a violation or the appearance 

of a violation, a sample of the lot is usually not collected. If 

your exam reveals a violation or potential violation, you 

should collect an official sample. Instructions on how to 

conduct a field exam are contained in "Guides to Inspection 

of ***" and Compliance Programs. The Sample Schedules 

in Chapter 4 also provide guidance on lot examinations for 

special situations.

SUBCHAPTER 5.2 - INSPECTION 

PROCEDURES

5.2.1 - PRE-INSPECTIONAL ACTIVITIES

Prior to the start of any inspection or investigation, you 

should conduct a number of activities. These will differ 

based on whether this is an inspection or an investigation. 

Review establishments history, e.g. previous EIRs, 

complaints, registration listing, recalls. The purpose of this 

review is to determine the location of the establishment and 

obtain an overview of the establishment's operations and 

products as well as an understanding of their compliance 

history. Consumer complaint review will also determine if 

there are any complaints with open assignments, or with 

the status “Surveillance information for next EI” that need 

to be closed. You should also review the establishment 

factory jacket to determine if there were any prior safety 

issues noted, e.g. documented Investigator safety incidents 

or whether any specific personal protective equipment is 

needed prior to the start of the inspection. If there has been 

a past personal safety incident, you should discuss with 

your supervisor and develop a Situational Plan prior to the 

start of the inspection. See IOM 5.2.1.4 – Personal Safety

Plan.

Prior to initiating any inspection, you should become familiar with the reporting requirements for the specific assignment, as well as the requirements of IOM Subchapter 

5.10.

If the inspection or investigation is a directed assignment 

from a Center, ORA headquarters or another program 

division, read the assignment and attached materials to 

assure you understand the assignment. If the inspection or 

investigation is being conducted in part or solely as a recall 

follow-up or complaint, refer to Chapter 7 (Recalls) or 

Chapter 8 (Investigations) of the IOM for additional 

guidance.

You should review the eNSpect assignment to determine if 

the Personal Safety Alert Indicator is set to yes for this 
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specific firm. The reason for the Personal Safety Alert 

should be listed in the Endorsement for the previous 

inspection and should be accompanied by a memo to the 

Establishment File Jacket. See IOM 5.2.1.3 eNSpect

Personal Safety Alert.

You should also review the applicable Compliance Program 

Guidance Manual(s) prior to the start of your inspection or 

investigation. Division of Domestic Human and Animal 

Food Operations (DDHAFO)The Centers have issued 

numerous guidance documents for industry. These 

documents are normally posted to the appropriate Center's 

Internet web site.

Subchapters 5.4-5.9 of the IOM contain additional, program 

specific pre-inspectional activities, which you should follow.

Imported products cross all program areas and our regulation of them does not stop at the border. Determine if 

there are any "import for export" follow-up assignments and 

be prepared to cover them during your inspection. See IOM 

6.2.3.4 for guidance. Please be alert to imported products 

whenever you make an inspection. During inspections of 

domestic firms, if you encounter imported products that 

appear adulterated, misbranded, counterfeit, tampered with 

or otherwise suspect, attempt to fully identify the product 

and the source of the imported products. Contact your 

supervisor and Division of Import Operations (DIO) if 

necessary.

5.2.1.1 - Pre-Announcements

Pre-announcements are mandatory for all medical device 

surveillance inspections in accordance with the criteria and 

instructions below and some BIMO inspections. Routine 

produce safety inspections should be pre-announced, 

unless otherwise directed. In some other program areas, 

pre-announcements may be made at the discretion of the 

program division. If you are going to visit facilities where 

livestock (including poultry) or wild animals are housed or 

processed, review IOM 5.2.10. In general, it may be 

inappropriate to pre-announce inspections of food 

establishments, blood banks, source plasma establishments and some BIMO inspections, but this too is subject 

to program division discretion. 

If a program division believes pre-announcing an inspection 

of an establishment will facilitate the inspection process,

then the procedures below for doing pre-announcements 

for medical device inspections should be followed. ORA's 

primary purpose for pre-announcing is to assure the 

appropriate records and personnel will be available during 

the inspection. It is not to make an appointment for the 

inspection. It should not be referred to as an appointment 

to inspect. When doing a pre-announcement, it is important 

you communicate to the establishment the purpose of the 

inspection and a general idea of the records you may wish 

to review. If you find neither the appropriate personnel nor 

records available, note this in your Establishment 

Inspection Report (EIR). 

In the case of drug inspections, if efforts to schedule a preannounced inspection are met with unreasonable delays by 

the establishment, including requesting a later start date 

without a reasonable explanation, it may constitute a delay 

of an inspection under section 501(j) of the FD&C Act [21 

U.S.C. 351(j)]. FDA will make reasonable accommodations 

for local conditions such as weather, holidays, or, where 

appropriate, manufacturing campaign schedules. 

However, if faced with an unreasonable delay by the 

establishment, you may call the responsible person’s 

attention to 501(j) of the Act. Talk with your supervisor to 

determine whether the length of a particular delay may be 

considered unreasonable, even in cases in which the 

explanation given for the delay may be reasonable.

The Program division may use this data in the future when 

considering whether this establishment should be eligible 

for pre-announced inspections.

The Produce Safety Network (PSN) should follow the preannouncement instructions provided in the Produce Safety 

Inspections assignment.

The following is the general outline for pre-announcement 

of medical device inspections. You are advising the 

establishment's management of the date and time you will 

be arriving at the establishment to conduct the inspection. 

The establishment has no authority to negotiate this. If you, 

as the investigator, feel the need to accommodate the 

establishment's request, be sure there are sound reasons 

for doing so and report them in your inspection report.

In the eNSpect “Pre-Announced / Unannounced to Firm” 

field select “Unannounced” when no notification was 

provided to the firm in advance of arrival at the firm for 

inspection. Select “Pre-announced” when the firm was 

notified of the inspection prior to the CSO arrival at the 

firm for the inspection. 

5.2.1.1.1 - BASIC PREMISES

Pre-announcement of inspections is to be applied only to 

establishments that meet specific criteria. Pre-announcement may be considered for establishments that manufacture both drugs and devices or biologics and devices. 

The eligibility of an individual establishment for pre-announced inspection is at the discretion of the inspecting 

Division using clearly described criteria. (See Criteria for 

Consideration) The program division does not have the 

discretion to decide the types of medical device 

establishments eligible for pre-announcement but may 

decide the specific establishments' eligibility because they 

meet the criteria.

The pre-announcement should generally be no less than 5 

calendar days in advance of the inspection. Should a 

postponement be necessary, the decision as to 

rescheduling rests with the investigator/team, but the new 

inspection date should not be later than 5 calendar days 

from the original date. Inspections may be conducted 

sooner than 5 calendar days if requested by or acceptable 
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to the establishment and if this date is acceptable to the 

investigator/team.

To participate in the pre-announcement portion of the program, establishments are expected to meet the 

commitment to have appropriate records and personnel 

available during the inspection.

Pre-announced inspections will not limit an investigator's 

authority to conduct the inspection. Inspections will be as 

thorough as necessary.

5.2.1.1.2 - CRITERIA FOR CONSIDERATION

Determine whether an establishment requires or qualifies 

for a pre-announced inspection (see section 5.2.1.1 PreAnnouncement). Examples include: 

1. Pre-market inspections (PMA, 510(k))

2. Foreign inspections

3. Instructed by Compliance Program, assignment or 

directive 

4. Quality System Surveillance Inspections

5. During Health Emergency Crisis; e.g.: epidemic, 

pandemic

5.2.1.1.3 - PROCEDURES

Procedures:

1. The investigator designated to conduct the inspection 

will contact the most responsible individual at the facility. 

You should leave a message requesting a return call if 

the most responsible person at the facility is unavailable 

at the time the call is made. The program division should 

use good judgment as to what is a reasonable time 

frame to await the return call.

2. Changes in dates should be kept to a minimum. If a 

change is made, a new date should be provided as soon 

as possible, which will facilitate the inspection and 

accommodate the investigator's schedule. The 

establishment should provide a valid reason for 

requesting a change in the start date. A valid reason 

should be the same as you would accept if presented 

with the information during an unannounced inspection.

3. Inform the establishment as to the purpose, estimated 

duration, and the number of agency personnel expected 

to take part in the inspection. The products or processes 

to be covered should be described if this will facilitate 

and be consistent with the objectives of the inspection.

4. When appropriate, specific records/personnel will be 

requested at the time the inspection is pre-announced.

5. The notification should be as specific as reasonably 

possible and specify the date for the start of the inspection.

6. Produce Safety Inspections should follow any additional 

instructions provided in the Produce Safety Inspection 

assignment.

Include in your EIR whether or not the inspection was preannounced and include information on any difficulties 

experienced in notification or accessing records or personnel, which should have been available as a result of preannouncing the inspection. For medical device establishment inspections, if not pre-announced, describe briefly in 

the EIR why not. If an establishment should become ineligible for pre-announcement, the endorsement of the EIR

should include this statement. This information will be 

necessary for making a determination regarding future preannounced inspections of the establishment. In addition, it 

is advisable to inform the establishment during the current 

and subsequent inspections of the action(s), which may 

have caused them to be ineligible for pre-announcement.

Subchapters 5.4-5.9 of the IOM contain additional, program 

specific pre-inspectional activities, which you should follow.

5.2.1.2 - Personal Safety

ORA considers the safety of investigators, inspectors and 

all those who meet with regulated industry to be of the 

utmost importance. Personal safety concerns are defined 

as those factors FDA employees should maintain awareness of which potentially affect their safety during an inspection, such a threatening situation; or where specific 

personal protective safety equipment is warranted; or 

where a particular inspection may be medically contraindicated for specific FDA personnel. When these conditions 

are noted during an inspection, the investigator should 

discuss the situation with their supervisor and ensure that 

the Personal Safety Alert is checked in FACTS/ eNSpect

and a Memo to the File is generated – see IOM 5.2.1.3. For

information concerning personal protective equipment, see 

IOM Subchapter 1.5.

Physical resistance to FDA inspections and threats to, or 

assaults on, FDA employees engaged in their work are 

extremely rare. However, there will be times you are confronted by unfriendly or hostile persons. ORA has offered 

various conflict resolution training courses to assist and 

prepare you for how to diffuse a situation. In most instances, conducting your activities with tact, honesty, diplomacy, and persuasiveness will be enough to diffuse the 

situation. While at times, you may have to adopt a firm 

posture, you should not resort to threats, intimidation, or 

strong-arm tactics. Refer to IOM 5.2.5.4 for Hostile and 

Uncooperative Interviewees.

Safety is the responsibility of all FDA employees, including

you, your supervisor and other Agency management. When 

you receive an assignment, it is important to evaluate the 

assignment not only in accordance with IOM Section 5.2.1, 

but also with respect to your personal safety. If you 

determine there is the possibility of a threat to your personal 

safety, consult with your supervisor. You and your 

supervisor should consider developing a Situational Plan in 

preparation for the inspection.

5.2.1.2.1 - PREPARATION

Below are some suggested items the program division may 

consider when preparing for your next assignment to 

assess if there are potential personal safety issues. This list 

is not meant to be all inclusive.
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1. Does the assignment involve working with other Federal 

Agencies such as U.S. Marshals, Federal Bureau of 

Investigations, and U.S. Customs in executing search 

warrants, seizures, etc.?

2. Does the assignment involve working with or contacting

FDA’s Office of Criminal Investigations (OCI)?

3. Does the assignment involve a firm where there is a 

suspicion and/or knowledge of questionable or illegal 

activities?

4. Does the assignment involve a suspected tampering 

and/or a visit to an individual’s residence?

5. What is the past history from a personal safety 

standpoint with the prior interactions with 

representatives of this firm? Have the FDA’s state 

counterparts or other Federal and/or local agencies 

indicated a concern for personal safety? What does the 

firm’s establishment file indicate about personal safety 

over the past inspections?

6. What is the location of the firm or the operation? Is it in 

an area which may be unsafe? Have the inspected firm 

or any of its employees been uncooperative with government officials?

7. Is the firm known to the Agency? Has the Agency any 

additional information which would assist in your 

evaluation?

If these questions and/or others result in a concern for your 

personal safety, then a Personal Safety Plan should be 

developed and approved by program division management 

before conducting the assignment. See IOM 5.2.1.4 –

Personal Safety Plan.

Due to the unlimited variability of potential safety situations, 

it is not feasible to prescribe in the IOM what to do in every 

instance. The decision of what to do in each individual 

circumstance rests with the investigator and their program 

division management. Your program division management 

is most familiar with the specific firm in question, the 

regulated industry, as well as other local Federal, State and 

Local officials who may be able to provide you additional 

information and assistance. In addition, the experience of 

your program division management combined with the 

various training courses on conflict resolution may also be 

consulted. Program divisions should notify OMPTO or 

OHAFO to inform headquarters of any potential safety 

concern, so that personal safety issues may be tracked. 

The headquarter component will also maintain a library of 

Personal Safety Plans which may also be of use to your 

Division. The headquarter component may be contacted at 

the following personal safety e-mail address:

orahqcsosafety@fda.hhs.gov.

5.2.1.2.2 - PHYSICAL 

RESISTANCE/THREATS/ ASSAULTS

If you receive physical resistance or threats, or if you sense 

the real possibility of an assault, disengage from the 

confrontation, get to safety, and call your supervisor 

immediately. Make careful and exact notes later of who said 

what to whom, who did what, and whether someone tried 

or succeeded in threatening, assaulting or taking 

information or equipment or samples from you. Be careful 

in any descriptions you give or write of such events, just as 

you are in recording other evidence that may result in a 

court case. Your safety is more important to the United 

States than the inspection or the sample collection. FDA will 

work with law enforcement government officials, e.g., the 

Federal Protective Service (FPS), FDA's Office of Criminal 

Investigations' (OCI) Special Agents, local police, or United 

States Marshals to assist an inspection team if there is a 

reasonable fear of danger to the investigator.

If you are assaulted (either physically or put in fear by 

threats of physical violence), your supervisor can summon 

local police, the Federal Protective Service (1-877-437-

7411), United States Marshals, FBI or contact OCI 

headquarters for assistance (301-294-4030). While OCI 

does not normally provide physical security in these cases, 

they will assist in threat evaluation based on specific facts 

and available criminal databases. OCI can also make 

contacts with local police and federal agencies based on 

previous established liaisons. If you have been assaulted 

or threatened and you are unable to reach your supervisor 

or other division management, you should contact the local 

police in the area where the assault or threat occurred. Be 

careful in any descriptions you give or write of such events, 

just as you are in recording other evidence that may result 

in a court case. Make sure that any inspected facility where 

weapons are observed, or where threats or assaults occur, 

is identified on that facility's Endorsement page of the 

inspection report for that facility and to your supervisor, so 

that Investigators or Agents who follow you into that facility 

will be alert to those possibilities. Your supervisor would 

also be responsible for checking the Personal Safety Alert 

box in FACTS and for beginning the notification process to 

alert other Federal or State agencies that also inspect the 

facility of the possible danger. For more information see 

IOM 5.2.1.3 Personal Safety Alert. For specific safety 

guidance related to inspections and interviews, see IOM 

5.2.5.4.2 Hostile and Uncooperative Interviewees.

In addition, in any instance where you have perceived a 

threat to your personal safety during an inspection, 

investigation or sample collection, you should exit the 

situation immediately and report it to your supervisor.

Potential threats may include geographic locations, 

concern about entering into a residence to conduct official 

business, or animals that are not caged or contained. You 

should then write a memorandum of the event in a factual 

manner including information pertaining to the who, what, 

when, where, and how of the event. Be careful in any 

descriptions you give or write of such events, just as you 

are in recording other evidence that may result in a court 

case. This memo will be filed in the official establishment 

file jacket and copies be sent to any and all resident posts 

and import program division offices who may interact with 

this firm. The memo will be filed on the opposite side of the 

folder from all other documents and will be a printed on eyecatching color paper in order for the document to be visible 

to the next Investigator. The memo should be retained and 

maintained within the division. A copy of the Memo 

documenting the personal safety situation should also be 
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sent to the headquarter component via 

orahqcsosafety@fda.hhs.gov. 

5.2.1.3 – eNSpect Personal Safety Alert

In eNSpect, the person creating an assignment may add an

"Active Personal Safety Alert" (PSA) on the "Firm" page. 

This field is editable any time after the assignment is 

created. The "Personal Safety Alert" tab on the "Firm 

Details" page in Management Services (FMS) should be 

checked for the existence of a PSA when assignments are 

created and before inspections are conducted. Only the 

FACTS Supervisor Role will allow for updating the Maintain 

Firms screen. This personal safety alert may be selected 

when there is a potential hazard identified:

1. Where a previous threat/assault or physical resistance 

occurred 

2. Where specific personal protective equipment is needed 

(respirators, etc.) 

3. Where there are specific medical considerations for a 

population of investigators (e.g. the firm manufactures a 

drug hazardous to women of child-bearing years or 

those with allergies to peanuts, penicillin, or other 

products.)

In any example listed where there is a Personal Safety 

Alert, the specific safety alert should be documented both 

in the Endorsement and in a Memo to the File. The memo 

should be flagged “MEMO TO FILE - PERSONAL SAFETY ALERT” and should provide the factual information to 

support why the investigator should be alerted to the safety 

issue. Be careful in any descriptions you give or write of 

such events, just as you are in recording other factual 

evidence that may result in a court case. The memo should 

be filed in the official establishment file jacket and copies

sent to any and all Resident Posts and import program 

divisions who may interact with the firm. The memo will be 

filed on the opposite side of the folder from all other 

documents and will be a printed on eye-catching color 

paper in order for the document to be visible to the next 

Investigator. The memo should be retained and maintained 

at the Program division office. A copy of the Memo 

documenting the personal safety situation should also be 

sent to orahqcsosafety@fda.hhs.gov . The supervisor 

and/or other program division management will be 

responsible for evaluating any corrective actions taken by 

the firm or individual to remove or stop the potentially 

dangerous situation or condition. Follow-up inspections at 

the facility should continue to document whether or not the 

safety situation continues exists. If the situation has been 

resolved (new management, dismissal of an employee, 

cessation of penicillin in a facility, etc.) the Personal Safety 

Alert should be removed from FACTS by the supervisor. 

5.2.1.4 – Personal Safety Plan

A Personal Safety Plan is an investigative tool developed 

to assist in managing and preparing for a potentially 

dangerous situation. Program division’s should develop a 

Personal Safety Plan when the conditions surrounding the 

specific inspection, investigation or sample collection 

indicate a plan is needed. The plan allows all those involved 

to carefully evaluate the specific inspection in order to 

prepare for a successful conclusion. Utilizing Personal 

Safety concepts prior to a potentially dangerous situation is 

part of the training programs of many other Federal 

Agencies. The plan should document what specific roles 

and responsibilities are needed to conduct the 

inspection/investigation or sample collection. The plan 

should also answer the questions: Who, What, Why, When 

and Where concerning the potential danger. 

There are seven principles to a Personal Safety Plan. 

These are:

1. Summary of Potential Hazards: This section of the 

personal safety plan includes all of the potential 

hazards, in a detailed description, that prompted the 

need for a personal safety plan. Be sure to answer the 

questions: Who, What, Where, When, and Why. Also 

include any specific hazards that require personal 

protective equipment or situations at the facility that 

may cause allergic reactions for investigators or 

analysts. Include in the section information from past 

inspection reports, discussions with previous FDA, 

State or local investigators, as well as any 

environmental or plant/facility specific information that 

would negatively impact a successful personal safety 

plan when initiated. 

2. Sources of Information: This section of the personal 

safety plan includes all the sources from which your 

potential hazards were collected. For instance, 

document which FDA investigator or State inspector 

supplied factual statements; state the documents or

databases from which you obtained information to

assist in your hazard summary. This section is 

important, as it documents factual evidence, similar to 

all of your other FDA factual inspection gathering 

information. 

3. Response Alternatives: This section will be the most 

important part of your plan because it includes all of the 

details of what will be done to mitigate the hazards. In 

this section, provide a list of factual, practical 

responses or options to consider. This will also allow 

your supervisor to see all the possible ways to handle 

the situation. The response plan should also outline all 

of the tools that you possess to assist you in handling 

the situation carefully, including training, experience, 

and other procedures you have at your disposal. Roles 

and responsibilities of all involved in the plan should be 

identified including those intended to be on-site, and 

those who will be off-site, and participating in the plan. 

4. Communication: provide all information about how 

communication will occur between on-site and off-site

participants; between those present on-site, and any 

emergency, law enforcement or medical responders. 

Also consider types of communication, e.g. code words 

for emergencies. 

5. Transportation: Provide information in the plan as to 

how travel to the facility will happen. Is there a 

coordination point? Do you intend to use Government 

marked or unmarked cars? Who will ride in each car? 

What route will be taken going to and leaving the 

facility? Consider where you will park the car when you 
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arrive at the facility. Consider what modes of 

communication will be used to communicate if multiple 

vehicles are used. 

6. Equipment: Include in this section all equipment 

needed to initiate this plan. Is personal protective 

equipment needed? Is there any special sampling 

equipment or other equipment needed? Include in this 

section, equipment such as communication tools, FDA 

forms, etc. Assure that the equipment needed is in full 

functioning mode. 

7. Emergency Exit Strategy: Describe in this section what 

the exit strategy will be in the event of an emergency. 

Consider emergency strategies for safety (issues), as 

well as any medical emergency. How will the 

emergency be communicated on-site and off-site? How 

do you exit the facility and return to your vehicle? Is 

there a scheduled meeting point to assure all are safe? 

The goal is to have no one left behind. Remember to 

contact your supervisor when you return to safety.

Once the plan has been completed, a debriefing of the 

situation should occur with all who were involved in the plan 

development. Evaluate what went well, what needed 

improvement, what would be done differently the next time. 

Evaluate whether the plan was successful and document 

lessons learned for the next time.

The Personal Safety Plan should be developed by the 

investigator, supervisor, other investigators who may be 

familiar with the facility, compliance officer, if needed, and 

any other individuals (Program Division or HQ experts, etc.) 

who may be able to assist in the depth, scope, and specifics 

of the firm in question. The decision of who should be 

involved in the development and approval of the plan is left 

to the program division’s discretion. 

Program division management and all involved in writing 

the personal safety plan should meet when necessary in 

order to assure a well-developed and understood personal 

safety plan. You and your supervisor should maintain 

contact during the execution of the personal safety plan. 

The supervisor should contact the employee during these 

personal safety situations at a predetermined frequency 

outlined in your plan. A debriefing session should be held 

following the execution of the plan. Discussions should 

include what actions worked well and where there are areas 

of improvement.

For foreign inspections where a Personal Safety Plan is 

warranted, headquarters POC will assist the inspection 

team. The inspection team’s management may also wish to 

participate so that there is clear understanding of what 

actions will be taken for the foreign inspection.

The Personal Safety Plan should be placed in the official 

establishment file jacket separate from any EIRs in the 

same location as any Personal Safety Alert memos. A copy 

of completed and executed Personal Safety Plans must be 

sent to orahqcsosafety@fda.hhs.gov in order to maintain a 

reference library of all Personal Safety Plans.

5.2.2 - NOTICE OF INSPECTION

Upon arrival at the firm locate the owner, operator or agent 

in charge of the establishment. This should be the top 

Management Official on site. Be certain of this individual's 

status. Introduce yourself by name, title and organization. 

Show your credentials to this person and present a properly 

signed, completed original of the FDA 482, Notice of 

Inspection or FDA 482d Request for FSVP Records. The 

FDA-482 or FDA 482d should have the address of the 

home district of the firm. *

If additional Agency personnel accompany you during the 

inspection, they must show their credentials to the top 

Management Official upon arrival at the site and issue a 

new FDA 482, Notice of Inspection or FDA 482d Request 

for FSVP Records. Only the additional Agency personnel 

need to sign the new FDA 482 or FDA 482d. Any additional 

FDA 482 or FDA 482d does not replace the initial FDA 482 

or FDA 482d. Any Agency personnel on a previously 

issued FDA 482 or FDA 482d will continue to be covered 

by their respective FDA 482 or FDA 482d. Submit copies 

of all the FDA 482(s) or FDA 482d(s) issued during the 

inspection with your EIR. Explain the purpose of your visit. 

Readily accept any management offer to have a 

representative accompany you on the inspection.

If non-FDA officials accompany you during your inspection 

and do not have authority to enter and inspect, you should 

obtain permission (preferably in advance) from the most 

responsible individual at the firm. Non-FDA officials and 

those who do not hold FDA credentials do not sign the FDA 

482 or FDA 482d. See IOM 5.1.1 and 5.11.4.3.3.

For multiple occupancy inspections in drug establishments, 

refer to IOM 5.1.1.11. Inspections of multiple firms, which 

are separate legal entities, should be reported under 

separate EIRs.

If faced with a refusal, or partial refusal of inspection,

proceed as outlined in IOM 5.2.5.4.

Any time an FDA 482 is issued, also issue an FDA 484 (at 

the conclusion of the inspection), Receipt for Samples, if 

you collect any samples at the firm. See IOM 5.2.4. See 

IOM 4.1.1.1 for instructions for issuance of the FDA 482 in 

certain sampling situations.

If you have concerns of when to or when not to issue the 

FDA 482, discuss with your supervisor.

*: For all firms within the State of Arizona, the Home District 

is Denver District. Home District boundaries are identified 

in Appendix E.

5.2.2.1 - Multiple Date Inspections

If your inspection covers more than one day, advise 

management at the close of each day you have not finished 
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the inspection and when you will return. Do this each day 

until you finish the inspection. An FDA 482 or FDA 482d is 

not required for each day of an inspection or when different 

individuals are interviewed. If there will be an extended 

period of time (i.e., a week or longer) before you can return 

to the firm to complete the inspection, be sure management 

is aware of the delay and discuss with your supervisor 

whether or not you need to issue another FDA 482 or FDA 

482d. 

5.2.2.2 - Inspection of Vehicles

If vehicles are present which are owned or leased by the 

firm being inspected and it is necessary to inspect the 

vehicles, the inspection of these is covered by the FDA 482, 

Notice of Inspection, you issued to the firm.

If vehicles (trucks, trailers, RR cars, etc.) which are not 

owned or leased by the firm are present and inspection is 

necessary, a separate FDA 482, Notice of Inspection, is 

required:

1. Issue the FDA 482 to the driver of the vehicle.

2. If the driver is not present and if, after a diligent search, 

he cannot be located, issue a separate FDA 482 jointly 

to the firm being inspected and to the firm whose name 

appears on the cab. Enter the license number of the 

vehicle on the FDA 482. Give the original FDA 482 to 

the firm and leave a copy in the cab of the vehicle.

3. If there is no cab present, prepare a separate FDA 482 

modified to read "*** to inspect unattended vehicle ***" 

and issue it to the firm being inspected as the "agent in 

charge" of the vehicle. Enter the license number of the 

vehicle, trailer or RR car number, etc., on the FDA 482. 

Should the firm being inspected refuse to accept the 

Notice, leave it in a conspicuous place in the vehicle. 

Describe the circumstances in your EIR.

5.2.2.3 - Follow-Up Inspections by Court 

Order

At times you may be instructed to conduct inspections of 

firms by authority of an injunction or other court order. This 

situation provides separate and distinct inspectional 

authority involving both the authority of the court order and 

the authority of Section 704 of the FD&C Act [21 U.S.C. 

374], each providing independent courses of action.

When assigned to conduct inspections under these 

situations, obtain a copy of the injunction or other court 

order bearing the filing stamp and all relevant signatures. 

Prior to starting the inspection study, the order thoroughly 

for any special instructions of the court. Your supervisor will 

assist you in determining the depth of the inspection 

necessary to cover all of the court requirements.

Take a clearly legible copy of the court decree (not 

necessarily a certified copy) with you to the firm to be 

inspected.

Present your credentials in the same manner as for any 

other EI. Issue the FDA 482, Notice of Inspection, modified 

to read, "Notice of Inspection is hereby given under 

authority of injunction (provide here the injunction number 

and/or other identification) against the firm and pursuant to 

Section 704 ***". Show the person to whom the FDA 482 

was issued a copy of the Order, and, read the following 

statement to that person.

"This inspection is being conducted under the authority of 

injunction (add the injunction number and/or other 

identification) (or other court order) granted by the United 

States District Court against this firm on (date). The 

inspection will cover all items specified in the decree. In 

addition to the inspection authority granted in the court 

decree, I am issuing you a Notice of Inspection under the 

authority of Section 704 of the Federal Food, Drug and 

Cosmetic Act which authorizes inspections of firms subject 

to that Act."

If the firm refuses access to records, facilities, or 

information for which the decree provides inspectional 

authority, read the pertinent section(s) or portion of the 

order to the person refusing so there will be no 

misunderstanding as to the requirements of the decree. If 

the person still refuses, report the facts to your supervisor 

as soon as possible so the court can be promptly advised 

of the situation. See IOM 5.2.5 for information on handling 

refusals.

When you prepare your EIR, describe the sequence of 

events in detail including exactly what happened and how 

you handled the situation. This documentation will help 

support any charge of violating the court order and/or 

Section 704 of the FD&C Act [21 U.S.C. 374].

The court order may require a report to the court. Discuss 

this with your supervisor since the division will normally 

handle this part of the requirement.

5.2.2.4 - Conducting Regulatory Inspections 

When the Agency is Contemplating Taking,

or is Taking, Criminal Action

You should not issue a Notice of Inspection if the agency is 

contemplating taking, or is taking, criminal action against a 

firm without first discussing the matter with your supervisor. 

Program division management will obtain advice from the 

Office of Chief Counsel and will allow or not allow, the 

inspection to proceed based on any considerations related 

to the criminal investigation. Decisions to inspect under 

such circumstances should be based on considerations of 

whether or not the request is consistent with FDA's 

responsibility to assure articles are not produced or 

distributed in violation of the Federal Food, Drug, and 

Cosmetic Act or other Federal law within FDA's jurisdiction. 

The program division should ensure these considerations 

are documented. In no circumstance should an inspection 

be conducted solely to obtain evidence to support a 

possible criminal case.

Inspections conducted in accord with this responsibility to 

protect the public and limited in scope to the authorizing 

statute are lawful even when criminal action is being 
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considered or pursued. The Fourth Amendment to the 

United States Constitution prohibits searches without a 

warrant supported by probable cause. One exception to the 

warrant requirement includes the inspection of industries 

long subject to close supervision and inspection, which are 

conducted under a statute dispenses with the need for a 

probable cause warrant. Three criteria must be met under 

this exception from the warrant requirement. First, the 

regulatory scheme authorizing the regulatory inspection 

must be supported by a substantial government interest. 

Second, regulatory inspections must be necessary to 

further the regulatory scheme. Third, the statute's 

inspection program, in terms of the certainty and regularity 

of its application, must provide a constitutionally adequate 

substitute for a warrant. 

Section 704 of the Federal Food, Drug, and Cosmetic Act 

[21 U.S.C. 374] is appropriately designed to allow 

regulatory inspections within appropriate limits. This 

provides the authority to inspect at reasonable times, within 

reasonable limits, and in a reasonable manner, 

establishments or vehicles being used to process, hold, or 

transport food, drugs, devices, or cosmetics. See IOM 

2.2.1.1. FDA’s normal inspection procedures provide 

guidance on what should be considered reasonable under 

Section 704. 

Should the evidence obtained during an inspection become 

material to a criminal case, it is possible a defendant will 

claim the use of statutory authority to conduct the inspection 

was a pretext to conduct an unlawful warrantless search. As 

long as the limits of Section 704 and normal establishment 

inspection procedures are followed, the possibility a court 

will find the inspection to be pretextual should be minimal. 

Deviations from these limits make it more likely a court 

would find the use of statutory authority to be pretextual and 

render the evidence obtained to be inadmissible. Concerns 

related to the conduct of an inspection while a criminal 

investigation is being considered or pursued should be 

discussed with the Office of Chief Counsel. 

It is the responsibility of the office generating the inspection 

assignment to inform the program division if a criminal 

action is ongoing or contemplated. There may be occasions 

when neither the office generating the inspection 

assignment nor the Program division conducting the 

inspection is aware the Office of Criminal Investigations

(OCI) is conducting a criminal investigation of a firm which 

is subject to regulatory inspection. OCI may determine it is 

not in the interest of the agency to disclose to other 

components of FDA the existence of its investigation, as 

long as OCI is not involved in the agency decision to 

conduct a regulatory inspection. However, OCI and other 

components of FDA may also share information as set out 

below.

5.2.2.5 - When Evidence of a Criminal 

Violation is Discovered in the Course of a 

Regulatory Inspection

There may also be occasions where you are conducting a 

regulatory inspection at a facility, and, in the course of the 

inspection, you discover evidence of a criminal violation. If 

this occurs, you should continue the regulatory inspection 

as you would under normal circumstances. See IOM 

5.2.2.4. Document the observation and notify your 

supervisor. The program division should refer the 

observations to OCI for their consideration. Evidence of the 

observation could be used in a criminal investigation, and 

the evidence could legally be disclosed to criminal 

investigators.

If you become aware of an ongoing criminal investigation, 

notify your supervisor. The program division should follow 

the Regulatory Procedures Manual (RPM) and notify the 

appropriate Center of any OCI involvement in a Center 

directed inspection. 

The discovery of evidence of a criminal violation may also 

be relevant to FDA's responsibility to assure articles are 

being produced in conformity with the Food, Drug, and 

Cosmetic Act. Additional inspections may be warranted. 

Such inspections should be planned and documented in 

accordance with the preceding section, "Conducting 

Regulatory Inspections When the Agency is Contemplating 

Taking, or is Taking, Criminal Action."

5.2.2.6 - Use of Evidence Gathered in the 

Course of a Criminal Investigation

The extent to which information gathered in the course of a 

criminal investigation may be shared with other 

components of FDA will vary with each case. Investigators 

should determine the extent of information sharing in 

accordance with the following guidelines.

Information and evidence gathered in the course of a 

criminal investigation may be shared with regulatory 

personnel, subject to two reservations:

1. Information obtained pursuant to grand jury subpoena 

or testimony may not be shared. Disclosure of such 

information to anyone other than individuals identified by 

the Department of Justice attorney involved could 

subject the individual making the improper disclosure to 

sanctions for contempt by the court. Only the court can 

authorize disclosure beyond these parameters. 

Information obtained by other means (search warrant, 

cooperative witnesses, surveillance, etc.) may be 

shared, subject to the following paragraph.

2. There may be a need to protect the confidentiality of the 

criminal investigation. For example, disclosure to 

regulatory investigators might prematurely disclose the 

existence of the criminal investigation or the identity of 

confidential informants. However, whenever you are 

calculating the need to protect the confidentiality of 

information gathered in the course of a criminal 

investigation through means other than the grand jury, 

you must consider whether it will be in the interest of 

public health to protect the confidentiality of that 

information.

Criminal investigators should consult their supervisors to 

determine whether disclosure should be made to regulatory 

investigators.
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5.2.2.7 - Use of Evidence Voluntarily 

Provided to the Agency

Criminal and regulatory investigators may share 

information and evidence voluntarily provided to FDA, 

without use of the regulatory inspection authority, search 

warrant, or subpoena. If criminal investigators decide not to 

share such information because of a need to protect the 

confidentiality of the criminal investigation, they should 

consider the potential impact on the public health of 

protecting the confidentiality of that information.

5.2.2.8 - Concurrent Administrative, Civil, and 

Criminal Actions

It may be appropriate to seek administrative and/or civil 

remedies against a firm or individual under investigation for 

criminal violations. There are many issues involved in 

determining whether such actions may proceed 

concurrently, or whether certain actions should proceed 

first. Each situation must be evaluated on an individual 

basis. If administrative and/or civil remedies are under 

consideration against a firm or individual also under 

investigation for criminal violations, representatives from 

the Center responsible for evaluating the administrative 

and/or regulatory action should meet with the Office of 

Criminal Investigations Headquarters staff to discuss 

issues related to the timing of administrative, civil, and 

criminal actions. The Office of Criminal Investigations and 

other components of FDA may share information subject to 

the reservations set out earlier.

5.2.2.9 - Working with a Grand Jury

Finally, if you are assigned to work with a grand jury, you 

should not participate in a regulatory inspection or other 

regulatory matter involving the same firm or individual(s). 

Such participation is contrary to long standing agency 

policy, might be unlawful, and could result in sanctions 

against the investigator and the agency. You should not 

participate in any regulatory matters that could result in 

improper disclosure of grand jury information, even after the 

grand jury investigation is closed. Grand jury proceedings 

remain secret even after they are concluded. Under no 

circumstances should you undertake such participation 

without first obtaining clearance from the Department of 

Justice attorney or the Office of Chief Counsel attorney 

assigned to the grand jury case. See IOM 2.2.7.3 for 

additional information on Grand Jury proceedings.

5.2.3 - REPORTS OF OBSERVATIONS

The FDA 483, Inspectional Observations (see Exhibit 5-5), 

FDA 483a, FSVP Observations (see Exhibit 5-18), and the 

FDA 4056 Produce Farm Inspection Observations (See 

Exhibit 5-17) are intended for use in notifying the inspected 

establishment’s top management in writing of significant 

objectionable conditions, relating to products and/or 

processes, or other violations of the FD&C Act and related 

Acts (see IOM 5.2.3.2) which were observed during the 

inspection. These observations are made when in the 

investigator's judgment, conditions or practices observed, 

indicate that any food, drug, device, or cosmetic have been 

adulterated or are being prepared, packed, or held under 

conditions whereby they may become adulterated or 

rendered injurious to health.

It is your responsibility to maintain the ability to attest in a 

legal forum that the observations were personally observed 

in conjunction with the supporting evidence. Inspectional 

observations should not be influenced, or appear to be 

influenced, by parties external to the inspection team, which 

could call into question the validity of the observations. This 

should not prevent you from consulting with your supervisor

or others, including the Centers, concerning your 

observations. The issuance of written inspectional 

observations is mandated by law and ORA policy. The FDA 

4056 will be issued upon completion of all produce farm 

inspections prior to leaving the premises. The FDA 483 and 

FDA 483a will not be used for produce farm inspections. 

See IOM 5.2.3.1.1 for instructions on documenting whether 

or not an FDA 4056 contains reportable observations. 

Be alert for specific guidance in assignments or 

Compliance Programs which may supplement the following 

general instructions.

FDA 483, FDA 483a and FDA 4056 should adhere to the 

following general principles:

1. Observations which are listed should be significant and 

correlate to regulated products or processes being 

inspected.

2. Observations of questionable significance should not be 

listed on the FDA 483, FDA 483a, and FDA 4056, but 

will be discussed with the firm’s management so that 

they understand how uncorrected problems could 

become a violation. This discussion will be detailed in 

the EIR or PFIR. 

FDA 483, FDA 483a, and FDA 4056 should have the 

following characteristics to be useful and credible 

documents:

1. Each observation should be clear and specific.

2. Each should be significant. Length is not necessarily 

synonymous with significance.

3. Observations should not be repetitious.

4. The observations should be ranked in order of 

significance.

5. All copies of the FDA 483, FDA 483a, and FDA 4056

should be legible.

If an observation made during a prior inspection has not 

been corrected or is a recurring observation, it is 

appropriate to note this on the FDA 483, FDA 483a, or FDA 

4056. 

Investigators and analysts should make every reasonable 

effort to discuss all observations with the management of 

the establishment as they are observed, or on a daily basis, 

to minimize surprises, errors, and misunderstandings when 

the FDA 483 or FDA 4056 is issued. This discussion should 

include those observations, which may be written on the 

FDA 483 or FDA 4056 and those that will only be discussed 
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with management during the closeout meeting. Industry 

may use this opportunity to ask questions about the 

observations, request clarification, and inform the 

inspection team what corrections have been or will be made 

during the inspection process. Investigators are 

encouraged to verify the establishment's completed 

corrective actions as long as the verification does not 

unreasonably extend the duration of the inspection.

Corrective actions observed and/or discussed during a 

produce safety inspection are annotated on the FDA 4056

as described in IOM 5.2.3.1.1 under Reportable 

Observations Made During the Inspection. Corrective 

actions not related to a significant observation are noted in 

the inspection notes and in the PFIR. 

Include the results of confirmed positive environmental 

samples on the FDA 483 or FDA 4056 if results are known 

prior to closeout for food inspections. The investigator 

should not prolong the inspection if the results are not 

known prior to close-out of the inspection.

There may be instances where same day discussion of 

observations may not be possible, for example, due to the 

volume of documents collected and document review 

reveals observations on a different day than the documents 

were collected or in other circumstances. When these 

instances occur immediately prior to the conclusion of the 

inspection the lack of a daily discussion of observations 

does not preclude listing of significant observations which 

were not previously discussed on the FDA 483, FDA 483a,

or the FDA 4056. 

eNSpect

eNSpect is an automated FDA 483,FDA 483a, FDA 4056, 

EIR and PFIR reporting system. Use eNSpect to generate 

the FDA 483, FDA 483a, or FDA 4056 where applicable cite 

modules exist. eNSpect should not be used to create an

FDA 483, FDA 483a or FDA 4056 during an inspection of 

a firm involving multiple commodity areas when cites do not 

exist for ALL of the commodity areas for which observations 

need to be included on the form. You should be able to write 

the entire FDA 483, FDA 483a, and FDA 4056 using 

eNSpect. 

Use eNSpect for all EIRs or PFIRs See IOM 5.11.4.

5.2.3.1 - Preparation of Form FDA 483, FDA 

483a, and FDA 4056

It is not necessary to complete all headings of the FDA 483,

FDA 483a, and FDA 4056 when multiple page forms are 

issued. Complete all headings on the first page and, on 

subsequent pages, only those necessary to identify the firm 

and dates inspected. An FDA 483, FDA 483a or FDA 4056

should be issued at the conclusion of the inspection and 

prior to leaving the premises. However, in preparing a 

complex FDA 483, FDA 483a or FDA 4056, it may be 

necessary to leave the premises and return at a later time 

to issue and discuss your inspectional observations. In this 

case, you should advise the firm’s management your 

inspection has not been completed and you will return to 

issue the FDA 483, FDA 483a, or FDA 4056 and discuss 

inspectional findings. There should be no unreasonable or 

unwarranted delays in issuing and discussing the FDA 

483,FDA 483a or FDA 4056. During the inspection, do not 

show the firm’s management a draft, unsigned copy of the 

FDA 483, FDA 483a, or FDA 4056 or an electronic copy of 

the form on your computer screen. You should issue only a 

signed FDA 483, FDA 483a, FDA 4056 at the closeout 

discussion with management.

5.2.3.1.1 - INDIVIDUAL HEADINGS

Form FDA 483 or FDA 483a: 

District Office Address and Phone Number - Legibly 

print the District address where the firm is physically 

located, regardless of program area or investigator duty 

station.. Include the district office commercial telephone 

number and area code.

For example, if a firm is located in Little Rock, Arkansas, 

then the district office would be Dallas District Office. See 

Appendix E for boundary maps.

Professional Stature for situations where firms express a 

concern during routine enforcement activities where an 

FDA 483 was not issued, or the activity is not an inspection.

Name and Title of individual to whom report is issued - 

Enter legal first name, middle initial and last name and full 

title of the person to whom the form is issued.

Firm name - Enter full, legal name of the firm, including any 

abbreviations, quotation marks, dashes, commas, etc.

Street address, city, state and Zip Code - Enter street 

address, city, state and Zip Code. (Not P.O. Box unless 

P.O. Box is part of the address such as on a Rural Route).

Date(s) of inspection - Enter actual or inclusive date(s) of 

inspection.

FEI Number - If the FDA Establishment Identifier is on the 

assignment, enter it here. If not readily available, leave 

blank.

Type of establishment inspected - Enter the types of the 

establishment, such as bakery, cannery, wholesale 

warehouse, drug repacker, salvage warehouse, etc.

Employee(s) signature and Employee(s) name and title

- The names of everyone who participated in the inspection 

with the issuance of an FDA 482 should be listed on the 

FDA 483 and FDA 483aeven if they are not available to 

sign the FDA 483 and FDA 483a. Each member of an 

inspection team should sign the FDA 483 and FDA 483a. 

However, absence of a team member at the conclusion of 

an inspection need not prevent issuance of the FDA 483or 

FDA 483a. See IOM 5.1.2.5.1. If you use an electronically 

generated FDA 483 or FDA 483a, assure you have a copy 

for the program division files -- an unsigned photocopy or 

printed duplicate is unacceptable. See IOM 5.2.3.6.2.
CHAPTER 5 INVESTIGATIONS OPERATIONS MANUAL 2023 

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Note: Use the FDA 483 instead of the FDA 4056 for 

inspections that only cover sprouts.

Form FDA 4056:

Name of State and Department (if acting under the 

commission with FDA) – If the FDA 4056 is used by a 

state acting under FDA commission, the name of the 

agency. For an FDA led inspection, place “N/A” in this 

section. 

District Office Address – 

• Domestic: the mailing address of the District Office 

where the farm is located. See Appendix E for 

boundary maps.

• Foreign: the mailing address for ORA/DFHAFO 

(12420 Parklawn Dr, Rm 2037 HFC-130, Rockville, 

MD 20857).

• State under FDA commission: the state agency 

office mailing address.

District Office Phone Number - Area code and phone 

number of the District Office for the inspected location, or 

of the state agency, if applicable.

Date(s) of Inspection - Enter actual date(s) of inspection. 

If multiple consecutive days, dates can be represented as 

an inclusive date range. If there is insufficient space, enter 

the first and last dates of inspection as a date range 

followed by an asterisk: “[MM/DD/YYYY] – 

[MM/DD/YYYY]*”. In the Continuation Sheet, enter 

“*DATES OF INSPECTION” followed by the full listing of 

actual dates of inspection.

FEI Number – Enter the FDA Establishment Identifier as 

per the Official Establishment Inventory (OEI). States 

under FDA commission can enter either the FEI number (if 

known) or the farm’s state ID number.

Last Name, First Name, Middle Initial and Title of 

Individual to Whom Report is Issued (Most responsible 

individual present) To - The legal name (listed as last 

name, first name, middle initial) and full title of the person 

to whom the form is issued. If the person does not have a 

middle initial, enter “NMI” for no middle initial. 

Farm Name (include business name, if different) - The 

full, legal name of the farm, including any abbreviations, 

quotation marks, dashes , commas, etc. If the farm uses 

another name for business purposes (i.e., a “dba”), include 

the other name also.

Owner/Operator – Full legal name of the person or 

corporate entity that owns and operates the farm. If the farm 

owner and operator are different, include both names.

Farm Mailing Address – Address, city, state, and zip code 

at which the farm receives mail. 

Farm Physical Location, If Different From Mailing 

Address – Location Identifiers Such As GPS 

Coordinates - Street address, city, state, and zip code 

where the farm is located. Do not use a P.O. Box unless 

P.O. Box is part of the address such as on a Rural Route. 

Include GPS coordinates of the main farm building, if 

available.

Type of Inspection - 

• Initial – first Produce Safety Rule inspection of the 

farm.“Initial” is not a standalone selection. All initial 

inspections are at a minimum either Routine or Forcause in addition to Initial. 

• Routine – normal surveillance inspection. 

• Follow-up – follow-up to a violative inspection; 

this would include an inspection of a farm 

completed after the state or FDA took a 

compliance or enforcement action.

• For-cause – inspection in response to a specific 

issue, such as an outbreak or violative sample, 

recall, complaint, or previous inspection findings 

(i.e. expedited next inspection). 

• Other (please specify) – use if additional 

explanation of the Type of Inspection is needed. 

Other should be selected with “Limited” when a full 

inspection was not performed, such as when “N/A” 

is entered under Crops Observed During 

Inspection or otherwise per assignment or 

compliance program guidance. 

Examples of selections: 

• Initial, Routine

• Initial, For-cause

• Routine

• Follow-up, For-cause

• For-cause

• For-cause, Other – Limited

• Initial, For-cause, Other - Limited

Crops Observed During Inspection - List the crops for 

which some element of growing, harvesting, packing, 

and/or holding were observed during the inspection. If the 

farm grows or handles other crops but those crops were not 

observed during the inspection, do not list them. Produce 

Safety Rule inspections should be conducted when 

covered activities on covered produce can be observed. As 

an exception, such as during an active outbreak response, 

enter “N/A” when no crops are observed.

Reportable Observations Made During the Inspection – The 

form has two checkboxes:

1. During an inspection of the operation (I) (we) did 

not observe any conditions and/or practices to be 

reported on this form.

2. During an inspection of the operation (I) (we) 

observed the following conditions and/or practices 

as described below.

 

One box will be checked during each inspection. If the first 
INVESTIGATIONS OPERATIONS MANUAL 2023 CHAPTER 5

5-23

box is checked, indicating no reportable observations, the 

rest of the form will be left blank except for page headers, 

the Sprouts checkbox (if applicable; see Sprouts section in 

this document), FDA REPRESENTATIVE SIGNATURE 

block, FDA REPRESENTATIVE(S) NAME AND TITLE 

(Print or Type) block, DATE ISSUED block, and any 

notation on the continuation sheet. 

If the second box is checked, the reportable observation(s) 

will be noted in the appropriate place on the form. If the 

observation is not related to one of the citations on the form, 

the observation will be noted in #46 “Other Observations” 

section of the form.

Each observation includes three elements:

Observation: check the box for the specific section of the 

regulation that applies to the observation noted. If the 

Observation box is checked, the Description section will 

also be completed. If an observation relates to more than 

one section of the regulation, record the observation in the 

FDA 4056 section that is the most appropriate. The 

observation should not be listed more than once. Consider 

whether items discussed with management during previous 

inspections need to be added as observations to the current 

FDA 4056 if no corrective action has been taken and 

conditions have worsened or present a risk to the product. 

Corrective action taken: the box is checked when a current 

observation is fully corrected before the close of the 

inspection. Do not check the box if you did not check the 

Observation box. Annotations accompanying a checked 

Corrective action taken box are “Reported Corrected, Not 

Verified” and “Corrected and Verified” (see Description 

below). It is best practice to verify the farm’s completed 

corrective actions as long as the verification does not 

unreasonably extend the duration of the inspection. 

Corrective actions that are not related to an observation 

recorded on the current FDA 4056 will not be annotated on 

the form. Document corrections to observations from prior 

inspections in notes and in the report (PFIR or inspection 

report summary). Do not check the Corrective action taken 

box if the observation is only partially corrected and/or if the 

farm has committed to corrective action but has not 

completed it by the close of the inspection. 

Description: include enough detail in the description section 

for the farm and other readers to understand the specifics 

of the observation and the significance (see IOM 5.2.3, 

5.2.3.1.4, and 5.2.3.2). Include a statement to indicate 

each observation’s rank in the format “This observation is 

ranked [rank number] of [total number of observations] in 

order of significance, with rank 1 being the most significant.” 

When there are multiple observations with distinct citations 

to include in one Description section, see Exhibit 5-17 for 

an example layout. For a handwritten FDA 4056, if you 

need additional room to write the description, end the 

Description section text with “...Continued below under the 

Continuation Sheet section...” The remainder of the text will 

be included on the continuation sheet. For eNSpect and 

PDF FDA 4056s, the Description section expands to 

accommodate all text entered. For eNSpect FDA 4056s, 

Description section contents will be laid out as described in 

this section when generated by the system.

 

If the farm has corrected the observation or has committed 

to correct it, the Description section should include only one 

of the following annotations:

1. Corrective Action: Reported Corrected, Not

Verified.

2. Corrective Action: Corrected and Verified.

3. Corrective Action: Promised to Correct.

 

Additional details regarding corrective action are not to be 

included on the FDA 4056. Include the information in the 

report (PFIR or inspection report summary). Do not 

annotate the FDA 4056 with the farm’s stated objections to 

an observation or to the form as a whole. 

 

Sprouts

Use this section of the FDA 4056 for observations related 

to the Sprouts subpart of the Produce Safety Rule (21 CFR 

112, Subpart M) when an inspection covers sprouts in 

addition to covering other types of produce subject to the 

PSR. Use the FDA 483 instead of the FDA 4056 for 

inspections that only cover sprouts. For all farms that do 

not engage in activities subject to Subpart M, check the box 

labeled “Check here if entity does not engage in growing, 

harvesting, packing, and/or holding of sprouts”. Do not 

check the box if the farm engages in the listed activities. If 

sprouts activities occur but were not inspected, enter in the

Continuation Sheet: “Sprouts (21 CFR Part 112, Subpart 

M) were not covered during this inspection.”

 

Other Observations

Use section (46) of the FDA 4056 to document any 

observations that do not fall under one of the other sections 

(1 – 45) identified on the form. In Description on the form, 

add the relevant citation and short description, as well as 

fully explaining the observation per guidance in Description 

above.

 

FDA REPRESENTATIVE SIGNATURE

• eNSpect generated version: electronic signature of 

lead investigator.

• PDF version: electronic signature of lead 

investigator or state inspector.

• Paper version: signature in ink of each investigator 

and/or inspector.

For more information, see IOM 5.2.3.1.2 – Signature Policy.

 

FDA REPRESENTATIVE(S) NAME AND TITLE - Name 

and title of all inspection team members (should match all 

members who signed the Form FDA 482(s), Notice of 

Inspection)

 

Date Issued – Date the inspection is completed and the 

form is issued.

 

Continuation Sheet

Use this section if needed to expand information from main 

sections of the form. Identify the section from which text is 
CHAPTER 5 INVESTIGATIONS OPERATIONS MANUAL 2023 

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continued, e.g. “*DATES OF INSPECTION...” or 

“Continued from Observation area #[insert applicable 

number, 1-46] on page [insert number]...” followed by the 

continued text. Otherwise, follow specific instructions 

pertinent to the added text, such as for sprouts (see above) 

or for amendments (see IOM 5.2.3.1.6). If there is nothing 

additional to note, “N/A” or “Intentionally left blank” should 

be entered.

 

Additionally, all amended FDA 4056s must include in the 

Continuation Sheet section “AMENDMENT” followed by the 

amendment number. The first amended FDA 4056 for the 

inspection will have “AMENDMENT 1” printed in the 

Continuation Sheet section. Any additional amendments 

required for the same inspection will be identified with the 

next sequential number.

If the second box is checked, the reportable observation(s) 

will be noted in the appropriate place on the form. If the 

observation is not related to one of the citations on the form, 

the observation will be noted in #46 “Other Observations” 

section area of the form. 

5.2.3.1.2 - SIGNATURE POLICY

Everyone present under FDA inspectional authority at 

issuance signs the first and last pages of the FDA 483 and 

initials each intervening page in the signature block. 

NOTE: if you are not using the official multi-part FDA 483 

form and a copier is not available, insert carbon paper to 

reproduce a signed copy of the FDA 483.

NOTE: If issuing the FDA 483 using eNSpect, the lead 

CSO’s signature will appear on all pages of the FDA 483 

and the remaining team members’ signature will appear 

on the last page.

On the FDA 4056, the signature is captured on one page 

in the FDA Representative Signature block. Everyone 

present under FDA inspectional authority during the 

inspection should be listed in the Representative(s) Name 

and Title box.

The FDA 4056 should be completed and signed 

electronically in eNSpect prior to printing and issuance. In 

circumstances where eNSpect cannot be used to 

complete the FDA 4056, complete the fillable PDF form. 

Only the lead FDA representative is to electronically sign 

the PDF FDA 4056. 

If electronic signature in eNSpect or the fillable PDF FDA 

4056 is not possible, print the FDA 4056 and all FDA 

representatives present at the close-out of the inspection 

are to sign in ink. 

When it is not possible to complete an FDA 4056 using 

eNSpect or the fillable PDF form, it is permissible to 

complete a hardcopy FDA 4056 in ink . Everyone present 

under FDA inspectional authority are to sign the document 

in ink. A copy of the signed FDA 4056 must be obtained 

for inclusion in the Produce Farm Inspection Report 

(PFIR), which is the equivalent of an EIR for produce farm 

inspections.

See IOM 5.2.3.6 -Distribution of the FDA 483 and FDA 

4056. 

5.2.3.1.3 - DATE ISSUED

Enter the date the form is actually issued to the firm’s 

management.

5.2.3.1.4 - OBSERVATIONS

Where applicable, when formulating each FDA 483, FDA 

483a, and FDA 4056 observation, answer Who (using titles 

or initials when necessary), What, When, Where, Why, How 

Much and How Often? Challenge each observation by 

asking “So What”? (regarding its significance)

Enter your reportable observations succinctly and clearly. 

Conditions listed should be significant and relate to an 

observed or potential problem with the facility, equipment, 

processes, controls, products, employee practices, or 

records. “Potential problems” should have a reasonable 

likelihood of occurring based upon observed conditions or 

events. Do not cite deviations from policy or guidance 

documents on your FDA 483, FDA 483a, and FDA 4056. 

As appropriate, FDA 483, FDA 483a, and FDA 4056

observations should include relationship of observations to 

a given population, for example, “Two out of 50 records 

examined were * * *” or “4 out of 12 bags examined were 

***.” When appropriate, an FDA 483, FDA 483a, and FDA 

4056 observation may refer to inadequate situations as 

long as you provide supporting facts (examples) or 

explanation as to why the condition, practice or procedure 

observed is inadequate.

It is preferred not to identify individuals or firms by name 

i.e., suppliers and consignees within the FDA 483, FDA 

483a, and FDA 4056. Where appropriate to support the 

FDA 483, FDA 483a, or FDA 4056 observation, identify the 

individual(s) or firm(s) by substituting other non-specific 

identifying information as below. Document your evidence 

in your EIR, fully explaining the relationship(s).

1. The lot number for a component received from or 

shipped to firm “A”.

2. The invoice number for a shipment from or to firm “A”.

3. A patient #, record #. See IOM 5.2.3.3 item 7.

4. The study number for a particular Clinical Investigator 

site.

5. Other necessary but non-specific identifying information

to show the observation’s relationship to a particular firm 

and/or individual.

Presently there are three ways to generate an FDA 483, 

FDA 483a, and FDA 4056. 

1. eNSpect

2. Traditional hard copy 

3. Electronic (non-eNSpect) version 
INVESTIGATIONS OPERATIONS MANUAL 2023 CHAPTER 5

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When using a traditional hard copy FDA 483 or electronic 

(non-eNSpect) version of the FDA 483, the current version 

of the 483 must be used. As of the printing of the current

IOM, the current version of the FDA 483 is dated 9/08.

5.2.3.1.5 - MEDICAL DEVICE INSPECTIONS

The following language should be inserted on the FDA 483 

in addition to the above statement: “The observations noted 

in this form FDA 483 are not an exhaustive listing of 

objectionable conditions. Under the law, your firm is 

responsible for conducting internal self-audits to identify 

and correct any and all violations of the quality system 

requirements.”

5.2.3.1.6 - CORRECTION OF FDA 483, FDA 

483a, and FDA 4056 ERRORS

These procedures do not pertain to adverse conditions 

noted and then corrected during the inspection. 

Observations of this type stand and should remain on the 

FDA 483, FDA 483a, and FDA 4056. 

The Inspectional Observations (FDA 483), Request for 

FSVP Records (FDA 483a) and Produce Farm Inspection 

Observations (FDA 4056) is of critical importance to both 

the Agency and regulated industry. Individual FDA 483s, 

FDA 483a, or FDA 4056 may become public through 

publishing in industry trade press, FOI inquiries, 

Headquarters postings and other means. Therefore, 

complete and accurate documentation of corrections to this 

official document is critical. Describe in your EIR the reason 

why the FDA 483, FDA 483a, or FDA 4056 was amended 

and your discussion with management regarding the 

amendment

5.2.3.1.6.1 - Errors Discovered Prior to 

Leaving the Establishment

Non-eNSpect, FDA 483, FDA 483a, and FDA 4056: 

1. Make handwritten changes to correct the error/s on the 

original FDA 483, FDA 483a, or FDA 4056 and initial the 

changes. Correct errors by striking through the 

erroneous text and entering the correct information (if 

any). When possible retrieve and destroy all 

uncorrected copies of the FDA 483, FDA 483a, or FDA 

4056 either provided to or produced (e.g., copied or 

printed) by the establishment.

2. If the establishment has photocopying equipment 

available and will provide you with a copy of the 

corrected original FDA 483, FDA 483a, or FDA 4056 

then obtain a copy of the corrected original document 

from the establishment. If the establishment has no such 

equipment or refuses to provide you with a copy of the 

original corrected FDA 483, FDA 483a, or FDA 4056 

then make the corrections, initial the changes and retain 

a copy of the corrected FDA 483, FDA 483a, or FDA 

4056 for your Division's official establishment file.

eNSpect FDA 483, FDA 483a, and FDA 4056

All corrections/deletions should be made in eNSpect. If 

there are technical difficulties which prevent you from 

issuing a modified eNSpect FDA 483, FDA 483a or FDA 

4056, you may handwrite the corrections on the original 

(maintain a copy for the EIR or PFIR) and inform the firm 

representatives that you will make corrections and provide 

them with the corrected eNSpect FDA 483, FDA 483a, or 

FDA 4046. 

1. Changes made to correct errors in the text of the 

observation will show on the face of the final FDA 483, 

FDA 483a, or FDA 4056. Changed Text deletions will 

remain visible as strike through and correction made. 

For example, “lot 1234 5678” – (select text, right click, 

select font and select strike-through) or from “lot 1234” 

to “lots 1234 and 5678” and bold the changes “lots 1234 

and 5678” 

2. If an entire observation is removed or the underlying 

citation is changed, incidental text will be used to add 

the statement "An observation concerning *** was 

removed [or the underlying citation was changed] based 

on discussions with management."

3. Addition of a new observation or changes to the 

observation. 

5.2.3.1.6.2 - Errors Discovered after Leaving 

the Establishment

Normally, you should not use the amendment process to 

issue additional FDA 483, FDA 483a, or FDA 4056 items

after the inspection has been closed out and you have left 

the premises.

1. Non-eNSpect, FDA 483, FDA 483a, FDA 4056: Discuss 

any errors with your supervisor. If necessary, a 

amended FDA 483, FDA 483a, or FDA 4056 will be 

prepared.

2. eNSpect FDA 483, FDA 483a, and FDA 4056: Discuss 

any errors with your supervisor. Make all 

corrections/deletions in eNSpect per 5.2.3.1.6.1. 

3. Issuing FDA 483, FDA 483a, or FDA 4056: Personally 

deliver the amended FDA 483, FDA 483a, or FDA 4056 

to the firm for discussion. If personal delivery is not 

practical, mail or email the amendment to the firm with 

a full explanation cover letter. Include a copy of the 

original FDA 483, FDA 483a, or FDA 4056, amended 

FDA 483, FDA 483a, or FDA 4056, and cover letter in 

the EIR or PFIR. In addition, you should call the person 

to whom the original FDA 483, FDA 483a, or FDA 4056 

was issued to discuss the change(s). Document your 

discussion in your EIR or PFIR. 

NOTE: The issuance of an amended FDA 483, FDA 483a,

or FDA 4056 in person or via mail/email does not change 

the inspectional end date. The inspectional end date 

remains as the date the original FDA 483, FDA 483a, or 

FDA 4056 was issued. The amended FDA 483, FDA 483a, 

or FDA 4056 should be issued as soon as possible.

FDA 483, FDA 483a, and FDA 4056 should be issued in 

eNSpect unless there are no commodity specific cites in 
CHAPTER 5 INVESTIGATIONS OPERATIONS MANUAL 2023 

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eNSpect, technical difficulties, or certain multiple 

commodity situations (see IOM 5.2.3) Other options are:

1. Electronic (non-eNSpect) version of the FDA 483, FDA 

483a, or FDA 4056. 

2. Handwritten FDA 483, FDA 483a, or FDA 4056. 

When using a handwritten or electronic (non‐eNSpect) 

version of the FDA 483, FDA 483a, or FDA 4056, the 

current version must be used.

5.2.3.2 - Reportable Observations

You should cite factual observations of significant 

deviations from the FD&C Act [21 U.S.C. 301], PHS Act, 21 

CFR, and other acts where FDA has enforcement authority 

unless these cites require concurrence or are specifically 

prohibited – see IOM 5.2.3.3 Non-Reportable 

Observations. Examples of these observations generally 

fall into two categories.

5.2.3.2.1 – Adulteration Observations

Review Sections 402, 501, 505(k), 601, and 704 of the 

FD&C Act [21 U.S.C. 342, 351, 355(k), 361, and 374]. 

Include specific factual observations of:

1. Foods, drugs, devices, or cosmetics consisting in whole 

or in part of filthy, putrid, or decomposed substances.

2. Undesirable conditions or practices, bearing on filth or 

decomposition, which may reasonably result in the food, 

drug, device, or cosmetic becoming contaminated with 

filth.

3. Insanitary conditions or practices which may reasonably 

render the food, drug, device, or cosmetic injurious to 

health.

4. Careless handling of rodenticides or pesticides.

5. Results of field tests (organoleptic examination of fish, 

crackout of nuts, etc.) if the results revealed 

adulteration.

6. Observations of faulty manufacturing, processing, 

packaging, or holding, of food, drug, or device products 

as related to current good manufacturing practice 

regulations including inadequate or faulty record 

keeping.

7. Observations of faulty can closures and/or deviations 

from recommended processing times and 

temperatures.

8. Deviations from the animal proteins prohibited in 

ruminant feeds requirements (21 CFR 589.2000).

9. Results of analytical laboratory findings which reveal 

adulteration.

5.2.3.2.2 - OTHER OBSERVATIONS

You may include other factual observations of significant 

deviations from the FD&C Act [21 U.S.C. 301], 21 CFR, 

Government Wide Quality Assurance Program (GWQAP) 

requirements, and other Acts as directed by CPs and other 

agency directives. In some cases, you may cite labeling 

deviations as directed below. This list is not all inclusive.

1. Observations indicating non-conformity with

commitments made in a New Drug Application, New 

Animal Drug Application, or in an antibiotic certification 

or certification exemption form. See Section 505 FD&C 

Act, [21 U.S.C. 355]. 

2. Observations, forming the basis for product nonacceptance under the Government Wide Quality 

Assurance Program (GWQAP). See IOM 5.2.3.5.

3. Deviations from blood and blood products labeling 

requirements as specified in 21 CFR 606.121 and 21 

CFR 640. 

4. Animal protein products, and feeds containing such 

products, that are not in compliance with the labeling 

requirements of paragraphs (c) through (f) of 21 CFR 

589.2000. See Section 403(a)(1) or 403(f) of the FD&C 

Act [21 U.S.C. 343(a)(1) or 343(f)]. 

5. Deviations from the applicable labeling regulations for 

human cells, tissue, and cellular and tissue-based 

products (HCT/Ps) as specified in 21 CFR 1271 and CP

7341.002. 

6. Observations indicating drug misuse, failure to maintain 

proper drug use records, and/or poor animal husbandry 

practices during drug residue investigations. See the 

applicable Compliance Program(s) for guidance.

7. Observations indicating non-conformity with the post 

marketing adverse drug experience reporting 

requirements as specified in 21 CFR 310.305, 314.80, 

314.98, 314.540, or 600.80 or other post marketing

requirements as specified in 21 CFR 314.81 or 600.14. 

See Sections 505 and 760 of the FD&C Act [21 U.S.C. 

355(k) and 379aa].

8. Observations indicating non-conformity with the Medical

Device Reporting requirements as specified in 21 CFR

803 {See Section 519(a) of the FD&C Act [21 U.S.C.

360i

9. Observations of non-conformity to the Medical Device

Tracking requirements as specified in 21 CFR 821 {See

Section 519(e) of the FD&C Act [21 U.S.C. 360i(e)]}

10.Observations of non-conformity to the Unique Device

Identification (UDI) requirements of 21 CFR 801

Subpart B and 21 CFR 830.

11.Observations of non-conformity to the Medical Devices 

Reports of Corrections and Removals requirements as 

specified in 21 CFR 806 {See Section 519(f) of the 

FD&C Act [21 U.S.C. 360i(f)]} should be verified with the 

program’s Division Recall Coordinator.

12.In general, observations indicating noncompliance with

medical device pre-market notification requirements

and pre- market approval requirement under FD&C

Act sections 510(k) and 515 [21 U.S.C. 360 (k) and

360e] respectively, should be included with the

prior confirmation of CDRH and/or CBER

13.21 CFR PART 200.10 does allow reporting observations

noted at a contract facility to the contracting facility. 

Before doing this, check with your supervisor to 

determine if this is appropriate.

14.Observations indicating non-compliance with LACF/

Acidified food registration and failure to file scheduled 

processes. Before doing this, verify lack of such, as 

covered in CP 7303.803A.
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15.Deviations from the applicable labeling requirements for 

outsourcing facilities as specified in Section 

503(B)(a)(10) of the FD&C Act.

16.Observations at animal food facilities that are not 

subject to animal food regulations (e.g., not required to 

register as a food facility) indicating food safety 

noncompliance with the FD&C Act adulteration or 

misbranding provisions in FD&C Act section 402 and 

403. See Compliance Program 7371.000: 

COMPREHENSIVE ANIMAL FOOD INSPECTION for 

more details.

5.2.3.3 - Non-Reportable Observations

Do not report opinions, conclusions, or characterize 

conditions as "violative." The determination of whether any 

condition is violative is an agency decision made after 

considering all circumstances, facts and evidence. See 

IOM 5.2.7 involving discussions with management at which 

time opinions may be discussed.

Do not quote Regulations (e.g., specific CFR sections) 

when listing items.

Do not report observations pertaining to:

1. Label and labeling content, except per IOM 5.2.3.2.2, 

items 2, 3, 4, 5, 10, and 12 above.

2. Promotional materials.

3. The classification of a cosmetic, animal grooming aid, or 

device as a drug.

4. The classification of a drug as a new drug or new animal 

drug. 

5. Non-conformance with the New Drug Regulations, 21 

CFR 312.1 (New Drugs for Investigational Use in 

Human Beings: Exemptions from Section 505(a)) 

unless instructed by the particular program or 

assignment.

6. The lack of registration required by Section 415 and 510 

of the FD&C Act. The lack of registration per 21 CFR 

1271 Subpart B Procedures for Registration and Listing, 

promulgated under Section 361 of the PHS Act.

7. Patient names, donor names, etc. If such identification 

is necessary, use initials, code numbers, record 

numbers, etc.

8. The use of an unsafe food additive or color additive in a 

food product.

9. The lack of approval, conditional approval, or indexing 

for an animal drug

The FDA 483 or FDA 483a should not include specific 

corrective actions taken by the firm in response to 

observations noted on the FDA 483, FDA 483a, or during 

the inspection except as described in IOM 5.2.3.4. These 

actions should be reported in the EIR.

Use eNSpect to document in the “Summary” and “General 

Discussion with Management” section Non-Reportable 

Observations, which you discussed with management. 

These objection-able conditions fall into three basic 

categories:

1. Observations of significant deviations from specific 

Laws and/or regulations, non-reportable items 1-9 

above. 

2. Observations of deviations from specific Laws and/or 

regulations, which in your judgment, are of 

“questionable significance” and “deemed not to merit 

inclusion on the FDA 483, FDA 483a, or FDA 4056,” but 

do warrant discussion with management.

3. Observations which in your judgment deviate from 

official published guidance, not regulations, but warrant 

discussion with management.

The reporting of observations for an FDA 483 or FDA 483a

in these 3 categories is as follows:

Category 1: You should select the appropriate eNSpect 

cite, verify or set the “Print type” to “Do Not Print,” and save 

the observation in the eNSpect database. This should be 

done even if there are no other reportable observations. For 

example, Lack of Food Registration as covered in IOM 

5.4.1.5.2 is not reportable.

Category 2 or 3: You should always report these two 

categories of observations which were discussed with 

management under the “General Discussion with 

Management” heading in the EIR as specified by IOM 

5.11.4.3.15. You have options in choosing how 

observations in category 2 are reported. You may select the 

appropriate cite in eNSpect, enter the “specifically” text 

regarding the observation, and discussion with 

management, set it to “Do not print”, save, and it will be 

automatically entered into the eNSpect when it is 

generated.

The second option which is also true for category 3 (i.e., 

there are no eNSpect cites for official guidance, only 

regulations) is the observation/s discussed with 

management may be entered directly into the eNSpect EIR 

under the “General Discussion with Management.”

Do not report opinions, conclusions, or characterize 

conditions as "violative." The determination of whether any 

condition is violative is an agency decision made after 

considering all circumstances, facts and evidence. ... 

Observations, which you discussed with management. 

These objection-able conditions fall into three basic 

categories: 1. Observations of significant deviations from 

specific Laws and/or regulations, non-reportable items 1-9 

above. 2. Observations of deviations from specific Laws 

and/or regulations, which in your judgment, are of 

“questionable significance” and “deemed not to merit

inclusion on the FDA 483, FDA 483a, or FDA 4056,” but do 

warrant discussion with management. 3. Observations 

which in your judgement deviate from official published

guidance, not regulations, but warrant discussion with 

management.
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5.2.3.4 - Annotation of the FDA 483 and FDA 

4056

Note: FDA 4056 are to be annotated per instructions in IOM 

5.2.3.1.1, Individual Headings, under Reportable 

Observations Made During the Inspection.

Offer to annotate the FDA 483 for all medical device 

inspections. The program division has discretion to 

annotate the FDA 483 in other program areas. BIMO 

inspections are generally excluded from annotations. 

Annotations of FDA 483 for inspections in other program 

areas may be done if both the establishment and the 

investigator/team believe annotation will facilitate the 

inspection process. When an FDA 483 is annotated it 

should be done in accordance with the guidance that 

follows.

Inform the establishment of the annotation program at 

some point prior to the final discussion with management. 

Determine from management whether they wish to have 

their FDA 483 observations annotated. It is voluntary on the 

part of the establishment. If the establishment does not 

want one or more observations annotated, you must honor 

the request.

The actual annotation of the FDA 483 should occur during 

the final discussion with management. The annotations are 

succinct comments about the status of the FDA 483 item. 

The annotations can be made after each observation, at the 

end of each page of the FDA 483 or at the bottom of the 

last page of the FDA 483 prior to the investigator's 

signature. See IOM 5.2.3 for discussions of FDA 483 

observations with management.

If the establishment has promised and/or completed a 

corrective action to an FDA 483 observation prior to the 

completion of the inspection, the FDA 483 should be 

annotated with one or more of the following comments, as 

appropriate:

1. Reported corrected, not verified.

2. Corrected and verified.

3. Promised to correct.

4. Under consideration.

The term "verified" means "to confirm; to establish the truth 

or accuracy". In this case, you must do the verification. In 

some situations, you will not be able to verify the corrective 

action unless there is further program division or Center 

review or until there is another inspection of the 

establishment.

The establishment's stated objections to any given 

observation or to the FDA 483, as a whole should not be 

annotated on the FDA 483. If firm does not wish to annotate

and FDA 483, then select no annotation in eNSpect, or if 

issued outside eNSpect, do not annotate. The EIR should 

include the establishment's objections to the observation 

and the fact the establishment declined to have the 

observation annotated.

When an establishment has promised corrections and 

furnishes a date or timeframe (without a specific date) for 

completion, then you may add "by xxx date" or "within xxxx 

days or months" in the annotation. Where the investigator 

and the establishment have "agreed to disagree" about the 

validity of an observation on the FDA 483, you may 

annotate this observation with "Under consideration" or with 

no annotation based on the establishment's desire.

All corrective actions taken by the establishment and 

verified by FDA should be discussed in detail in the EIR. 

5.2.3.5 - Government Wide Quality Assurance 

Program (GWQAP)

When performing product acceptance examinations under 

the GWQAP, you must discuss all deficiencies with 

management and report these deficiencies in writing on the 

FDA 483. This includes all deficiencies related to the FD&C 

Act as well as deficiencies in complying with contract 

requirements, which result in non-acceptance. There must 

be a clear differentiation on the FDA 483 between these two 

types of deficiencies.

Enter the FD&C type deficiencies (GMP deviations, etc.) 

first on the FDA 483. If there are deficiencies in contract 

provisions, draw a line across the sheet and add a heading 

"The Following Additional Contract Non-Conformances 

Were Observed." Enter each deficiency, which forms a 

basis for non-acceptance, followed by the reference to the 

applicable contract requirement or specification.

5.2.3.6 - FDA 483, FDA 483a, and FDA 4056

The FDA 483, FDA 483a and FDA 4056 should be issued 

to the most responsible person available at the close of the 

inspection. 

A copy should be sent to the top management of the firm

including foreign management, unless the individual to

whom you issued the original is the top official of the firm.

Per 5.2.3.1., FDA 483, FDA 483a and FDA 4056

should be issued at the conclusion of the inspection 

and prior to leaving the premises.

The signed FDA 483, FDA 483a and FDA 4056 can 

be issued in the following ways:

1. Physical paper copy. Be sure printed versions of 

the signed FDA 483s, FDA 483a, and FDA 4056s 

are legible.

2. Electronically by email as a PDF attachment 

(on site prior to leaving the premises). The 

FDA 483, FDA 483a, and FDA 4056 must be 
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sent in a manner that protects Trade Secret and 

Confidential Information.

3. Electronic Media transfer to the firm (e.g., 

USB, CD/DVD...). Follow all IT security 

policies and procedures when using 

electronic media, including FDA policy with 

portable media devices available here 

Cybersecurity - Information-SystemsSecurity-and-Privacy-Polic.pdf - All 

Documents (sharepoint.com) and IOM 

5.3.8.3.1 - ELECTRONIC RECORDS and 

IOM 5.3.8.3.3.1 - IDENTIFYING AND 

SECURING ELECTRONIC STORAGE 

MEDIA

If the FDA 483, FDA 483a or FDA 4056 is issued 

electronically, document your method of issuance 

and discussion with management in your regulatory 

notes per IOM 5.2.7 – Discussions with 

Management.

5.2.3.6.1 – Non-eNSpect generated FDA 483, 

FDA 483a, and FDA 4056

Before leaving the premises at the end of the EI, print and

present the issued FDA 483, FDA 483a, or FDA 4056 to 

the most responsible individual Upload into eNSpect one 

copy of any signed, modified, and/or amended FDA 483, 

FDA 483a or FDA 4056, issued to the firm. 

5.2.3.6.2 – eNSpect generated FDA 483, FDA 

483a, and FDA 4056

Before leaving the premises at the end of the EI, present 

the printed signed FDA 483, FDA 483a, or FDA 4056 to the 

most responsible person available.

5.2.4 - RECEIPT - FACTORY SAMPLES

You must issue an FDA 484, Receipt for Samples, if you 

collect any physical sample during an inspection. At the end 

of the EI and prior to leaving the premises, issue the original 

FDA 484 to the same individual who received the FDA 482. 

(See IOM 4.2.5) If this person is not available, give it to 

someone else who meets the definition of owner, operator, 

or agent in charge. Submit an exact copy with the EIR. Do 

not comment on type of examination expected or promise 

a report of analysis.

5.2.4.1 - Items Requiring Receipt

Issue an FDA 484 for any item of food, drug, device, or 

cosmetic actually removed from the establishment.

NOTE: A receipt must always be issued to anyone from 

whom you obtain Rx drugs. This includes individuals as well 

as firms. See IOM 4.2.5.4 and IOM 4.6.2.40. 

The following are examples of exhibit materials also 

requiring a Receipt for Samples:

1. Air filter pads,

2. Rodent pellets, nesting material, package cuttings, 

insects, insect frass and

3. Any other physical evidence actually removed from the 

plant, including in-line and environmental swabs.

5.2.4.2 - Items Not Requiring Receipt

Do not issue an FDA 484 for:

1. Items or materials examined during the inspection but 

not removed from the establishment (report adverse 

results of analysis of materials on FDA 483 and FDA 

4056 as indicated in IOM 5.2.3.2),

2. Labels and labeling, including promotional material,

3. Photographs taken during the inspection, or

4. Record(s): including production, quality control, shipping and interstate records.

Firm management may request copies of documents or 

records you obtain from their firm. There is no objection to 

supplying them.

See IOM 5.3.8.5 for procedures when a firm requests a 

receipt for records copied during an inspection or 

investigation.

5.2.5 - INSPECTION REFUSAL

A refusal of inspection is refusal to permit entry or other 

action that prohibits the investigator from obtaining 

records and information to which FDA is entitled under the 

law. Discuss all refusals with the most responsible official 

present at the establishment at the time the refusal was 

made. See IOM 4.2.3 for information regarding refusal to 

permit sampling.

For a refusal experienced during an inspection conducted 

under section 704 of the FD&C Act, FDA must 

demonstrate that the inspection was attempted to be 

conducted at a reasonable time, in a reasonable manner, 

and within reasonable limits to show you exercised 

prudence to avoid refusal. You must have presented your 

credentials and given the responsible individual a properly 

prepared and signed Notice of Inspection, FDA 482 for 

domestic inspections. 

Inspection refusals may take several forms. All refusals to 

permit inspection must be reported in your EIR under the 

"Refusals" heading.
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In the case of drug inspections, inspection refusals, as well 

as delaying, denying, or limiting your ability to conduct the 

inspection, may cause a drug to be deemed adulterated 

under Section 501(j) of the FD&C Act [21 U.S.C. 351(j)]. 

See subsection 5.5.5.8 in Subchapter 5.5 (Drugs) for 

further guidance on responding to these situations.

For foreign food inspections, section 807(b) of the FD&C 

Act (21 U.S.C. 384c(b)), authorizes FDA to refuse 

admission of a food “into the United States if it is from a 

foreign factory, warehouse, or other establishment of which 

the owner, operator, or agent in charge, or the government 

of the foreign country, refuses to permit entry of United 

States inspectors or other individuals duly designated by 

the Secretary, upon request, to inspect such factory, 

warehouse, or other establishment.”

5.2.5.1 - Refusal to Permit Inspection

When you are faced with a refusal of entry, call the 

responsible individual’s attention to the applicable sections 

of the Act (e.g., sections 301(f) and 704 of the FD&C Act 

[21 U.S.C. 331 (f) and 374] and section 351(c), 360A(a), 

(b) and (f); 360B(a); and 361(a) of the Public Health 

Service Act. Applicable sections of these laws are listed 

on the front and back of the Form FDA 482. If entry is still 

refused, leave the completed Form FDA 482, leave the 

premises and contact your supervisor immediately for 

instructions. 

Note: CPG Sec. 130.100 Inspectional Authority; Refusal to 

Permit Inspection 

In the case of drug inspections, if the person refuses entry 

or delays, denies, or limits your ability to conduct the 

inspection, also call the person’s attention to Section 

501(j) of the FD&C Act [21 U.S.C. 351(j)] (an adulterated 

drug could lead to further prohibited acts under 301(a), 

(b), (c) [21 U.S.C. 331(a), (b), (c)]). See subsection 5.5.5.8 

in Subchapter 5.5 (Drugs) for further guidance on 

responding to these situations. 

For international inspections, a refusal to permit inspection 

may result in a recommendation for regulatory action (e.g., 

Import Alert, cancellation of Food Facility Registration). 

Refusal to permit an international inspection should be 

reported in a memo uploaded into an Operation 15 – 

Foreign Investigation and should not be reported as a 

“Washout” in eNSpect

5.2.5.2 - Refusal to Permit Access to or 

Copying of Records

If management objects to the manner of the inspection or 

coverage of specific areas or processes, do not argue the 

matter but proceed with the inspection. However, if 

management refuses to permit access to or copying of any 

record to which you are entitled under law, call attention to 

Section 301(e) of the FD&C Act [21 U.S.C. 331] or 

applicable sections of the PHS Act. If management still 

refuses, proceed with the inspection until finished.

In the case of drug inspections, if management refuses 

access to or copying of any record to which you are entitled 

under law, in addition to Section 301(e) noted above, call 

attention to Section 501(j) of the FD&C Act [21 U.S.C. 

351(j)] (an adulterated drug could lead to prohibited acts 

under 301(a), (b), (c) [21 U.S.C. 331(a), (b), (c)]). 

Furthermore, if during a drug inspection management 

delays producing records you request to which you are 

entitled under law, without giving a reasonable explanation 

such as requiring sufficient time to compile a large volume 

of records or translate the records into English, you may 

call their attention to 501(j) of the FD&C Act. Similarly, if 

management limits your access to or ability to copy any 

record to which you are entitled under law, you may call 

their attention to Section 501(j) of the FD&C Act. See 

subsection 5.5.5.8 in Subchapter 5.5 (Drugs) for further 

guidance on responding to these situations. 

It is not an inspection "refusal" when management refuses 

to provide information e.g., formulation, lists of shipments

and manufacturing codes, unless it is specifically required 

by law or regulation. If the refusal is such that you cannot 

conduct a satisfactory inspection, discuss with your 

supervisor if a Warrant for Inspection should be requested.

5.2.5.3 - Refusal after Serving Warrant

If you have been refused entry, obtained a warrant, tried to 

serve or execute it and are refused entry under the warrant, 

inform the person, the warrant is a court order and such 

refusal may constitute contempt of court. If the warrant is 

not then immediately honored (entry and inspection 

permitted), leave the premises and promptly telephone the 

facts to your supervisor.

If you have served the warrant and during the inspection 

you encounter partial refusal or resistance in obtaining 

access to anything FDA is authorized to inspect by the 

warrant, inform the firm that aspect of the inspection is part 

of a court order and refusal may constitute contempt of 

court. If the warrant is not then immediately honored, leave 

the premises and promptly telephone the facts to your 

supervisor.

5.2.5.4 - Hostile and Uncooperative 

Interviewees

More often than not, investigations or inspections are 

conducted in a reasonable atmosphere. Nonetheless, there 

will be times you are confronted by unfriendly or hostile 

persons.

Your activities must always be conducted with tact, 

honesty, diplomacy, and persuasiveness. Even though you 

must at times adopt a firm posture, do not resort to threats, 

intimidation, or strong-arm tactics.

Many times, a hostile or uncooperative attitude on the part 

of individuals being interviewed results from fear, timidity, 

or previously distasteful encounters with law enforcement 
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personnel. In most cases a calm, patient, understanding 

and persuasive attitude on your part will overcome the 

person's reluctance or hostility. Often the mere fact you 

patiently listen while individuals share their views will make 

them receptive to your quest.

5.2.5.4.1 - INDICATORS

Normally you have no way to predict the nature of the 

individuals you meet. However, there are often indicators, 

which can alert you, such as:

1. Establishment inspection reports, endorsements or 

memorandums may show situations where 

investigators encountered belligerent or hostile 

individuals. These reports may be FDA reports and/or 

State contract reports, if available.

2. Discussions and conversations with FDA, federal, state 

and local inspectors and investigators may reveal 

instances where uncooperative individuals and problem 

situations were encountered.

3. The nature of the assignment, program or information 

requested may indicate some degree of caution is 

needed.

4. A firm located in an area with a reputation for 

unfriendliness to law enforcement personnel should 

alert you some employees of the firm may be less than 

cooperative during the investigation.

If you find yourself in a situation which, in your judgment, 

indicates violence is imminent, stop the operation and make 

an exit as soon as possible. Immediately report the facts to 

your supervisor.

5.2.5.4.2 - SAFETY PRECAUTIONS

The FDA recognizes there are situations where it is 

advisable to take precautions for your personal safety. In 

those, consult your supervisor. Some procedures, which 

may be utilized to minimize the danger, include:

1. Inspections or investigations carried out by a team of 

two or more persons.

2. Consider whether or not the use of an unmarked 

government car would be more beneficial to assist you 

in your inspection in lieu of a marked government car.

3. Request additional information from your State and/or 

Local Agencies who also regulate and inspect the 

facilities in question. In many instances, your State 

counterparts may have more information regarding the 

facility. This may be especially helpful for those firms 

that FDA has not yet inspected but were inspected by 

your State counterparts.

4. Each inspection team should be assigned one FDA cell 

phone or alternate communication device. While we 

recognize that some Investigators carry a personal cell 

phone, FDA strongly suggests that your personal cell 

phone not be utilized to contact the firm or firm’s 

management. In some instances, such uses in the past 

have resulted in later inappropriate contacts from the 

firm to the individual FDA Investigator.

5. Request assistance from local law enforcement 

agencies prior to or during investigations. This 

assistance may include information about the facility you 

are to inspect, assistance with communication devices, 

or police protection, if the police jurisdiction allows for 

such an action.

6. In potentially hazardous investigations such as 

methadone or schedule II Class Drugs, two 

investigators may be used and personnel from the U.S. 

Drug Enforcement Administration, State, or local law 

enforcement agencies may be requested to accompany 

you.

5.2.5.4.3 - PROCEDURES WHEN 

THREATENED OR ASSAULTED

In instances when you are actually assaulted or threatened, 

you should immediately notify your supervisor. Your 

supervisor can summon local police, United States 

Marshals, or contact OCI headquarters for assistance (301-

294-4030). OCI can make contacts with local police and 

federal agencies based on previous liaison. Also, the 

program division should notify 

orahqcsosafety@fda.hhs.gov. 

If you are physically attacked, you have the same recourse 

as any other citizen as well as the benefit of federal laws 

protecting government officials while in the performance of 

their official duties. If you are physically attacked, you 

should get to safety, call your supervisor, report the incident 

and seek medical attention if needed. Remember that the 

medical attention you receive may be used as 

documentation for the Agency in support of any legal action 

taken against the firm or the individual.

5.2.5.4.4 - NOTIFICATION OF FBI AND US 

ATTORNEY

It is a federal crime for anyone to kill, assault, resist, 

oppose, impede, intimidate, or interfere with, a federal 

official in the performance of their official duties.

In case of assault or threat against you, notify your 

supervisor immediately, so the facts can be submitted to 

the Federal Bureau of Investigations and the U.S. 

Attorney's office for immediate action.

The referenced sections in Title 18 of the U.S. Code are:

1. Title 18 U.S.C.A. Section 111, which provides:

"111. Assaulting, resisting, or impeding certain officers 

or employees.

Whoever forcibly assaults, resists, opposes, impedes, 

intimidates, or interferes with any person designated in 

Section 1114 of this title while engaged in or on account 

of the performance of his official duties, shall be fined 

not more than $5,000 or imprisoned not more than 

three years, or both.

Whoever, in the commission of any such acts uses a 

deadly or dangerous weapon, shall be fined not more 

than $10,000 or imprisoned not more than ten years, or 

both.   ".

2. Title 18 U.S.C.A. Section 1114, which provides:

"1114. Protection of officers and employees of the 

United States.
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Whoever kills ** *** or any officer or employee of the 

Department of Health and Human Services or of the 

Department of Labor assigned to perform investigative, 

inspection, or law enforcement functions while 

engaged in the performance of his official duties, shall 

be punished as provided under sections 1111 and 1112

of this title.  ".

See Title 18 of the US Code Sections 111 and 1114 for the 

complete text. 

5.2.6 - INSPECTION WARRANT

A refusal to permit inspection or a refusal to permit access 

to or copying of records may invoke criminal provisions of 

sections 301(e) and 301(f) of the FD&C Act [21 U.S.C. 

331(e), (f)]. Furthermore, in the case of drug inspections, 

delaying, denying, limiting, or refusing an inspection may 

invoke criminal provisions of sections 301(e) and 301(f) 

[21 U.S.C. 331(e), (f)]. Depending on the individual 

situation, instances of refusal may be met by judicious use 

of inspection warrants.

Instructions for obtaining warrants are contained in the 

Regulatory Procedures Manual, Chapter 6-3. See your 

supervisor for information and instructions.

You are operating as an agent of the court when you serve 

an inspection warrant and it must be executed expeditiously 

once served. See IOM 5.2.5.3 for guidance on how to

handle any refusal after obtaining a warrant.

In situations where a potential problem is anticipated with 

the service of a warrant, the Program division should

consider sending a Supervisory Consumer Safety Officer or 

Compliance Officer and a U.S. Marshal with the 

Investigator to assist and supervise the serving of the 

warrant.

After obtaining an Inspection Warrant, return to the firm 

and:

1. Show your credentials to the owner, operator, or agent 

in charge,

2. Issue the person a written Notice of Inspection (FDA

482),

3. Show that individual the original signed Inspection 

Warrant,

4. Give him/her a copy (not the original) of the warrant.

The copy you provide need not be signed by the issuing 

judge, but the judge's name should be typed on the copy.

Follow the procedures of the court or U.S. Attorney 

involved, if their methods differ from the above.

When an inspection is made pursuant to a warrant, a 

Return showing the inspection was completed must be 

made to the Judge (or U.S. Commissioner or Magistrate) 

who issued the warrant. The Return, executed on the 

original warrant, should be made promptly and usually no 

later than 10 days following its execution.

5.2.7 - DISCUSSIONS WITH MANAGEMENT

After completion of the inspection, meet with the most 

responsible person available to discuss the objectionable 

conditions observed. Objectionable conditions may be 

identified as reportable (See IOM 5.2.3.2) or non-reportable

(See IOM 5.2.3.3). During the discussion, be direct, 

courteous, and responsive with management.

Explain the significance of each item and relate to the 

applicable sections of the laws and regulations 

administered by the FDA. 

If significant deviations are observed during the inspection, 

you should inform management during the closeout 

discussion, the conditions observed may, after further 

review by the Agency, be considered to be violations of the 

FD & C Act or other statutes. Legal sanctions available to

FDA may include seizure, injunction, civil money penalties 

and prosecution. 

Significant deviations observed during a foreign inspection 

could result in a facility’s product(s) being refused or 

detained upon entry into the United States. 

Do not be overbearing or arbitrary in your attitude or 

actions. Do not argue if management voices a different view 

of the FDA 483 observations. Explain, in your judgment the 

conditions you observed may be determined by the FDA, 

after review of all the facts, to be violations. Make clear the 

prime purpose of the discussion is to call attention to 

objectionable practices or conditions, which should be 

corrected.

Determine management’s intentions regarding correcting 

objectionable conditions, including time frames. They may 

propose corrections or procedural changes and ask you if 

this is satisfactory. If this involves areas where your

knowledge, skill, and experience are such that you know it 

will be satisfactory, you can so advise management. Do not 

assume the role of an authoritative consultant. Do not 

recommend the product or services of a particular 

establishment. If asked to suggest a product or consulting 

laboratory, refer the inquirer to a classified directory or trade 

publications and or organizations. Advise management if 

FDA receives an adequate response to the FDA 483 or 

FDA 4056, or other objectionable conditions, within 15 

business days of the end date of the inspection, it may 

impact FDA’s determination of the need for subsequent 

action. 

Report in your EIR all significant conversations with 

management or management representatives. In most 

instances it is not necessary to quote management's 

response verbatim. Paraphrasing the replies is sufficient. 

However, if the situation is such that quoting the reply or 

replies is necessary, enclose them in quotation marks.

5.2.7.1 - Protection of Privileged Information

You have certain responsibilities under the FD&C Act, 

Section 301(j); Sections 359(d) and 306(e) of the Public 
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Health Service Act; and Section 1905 of the Federal 

Confidential Statute (18 U.S.C. 1905) regarding protection 

of confidential material obtained during your official duties. 

See IOM 1.4.

Do not volunteer information about other firms or their 

practices. Ignore casual exploratory questions or remarks 

from management about competitors or their processes. 

Your casual and seemingly innocuous remarks may reveal 

privileged information. Therefore, be alert and avoid 

voluntarily or unknowingly divulging information, which may 

be privileged or confidential and possibly compromise 

FDA's and your own integrity.

Management often request copies of any documents or 

records you obtain from their firm. There is no objection to 

your supplying these. When management requests copies 

of photos taken by you in a plant, follow IOM 5.3.4.5.

You may encounter situations when management invites 

outside individuals to observe the inspectional process 

(e.g., representatives from the press, trade associations, 

congressional staff, other company officials). As discussed 

in Section 5.1.4.3 of the IOM, the presence of 

representatives invited by the firm should not disrupt the 

inspectional process. You are to continue the inspection in 

a reasonable manner.

If the firm allows invited individuals to photograph, 

videotape, or prepare audio recordings during the inspection, you should make every effort to protect privileged 

information in your possession. However, it is the Agency's 

position that it is the firm's responsibility to protect 

confidential and/or proprietary information observed or 

recorded by those individuals invited by the firm. Where 

applicable, refer to IOM 5.3.5 for additional procedures on 

how to prepare your own recording in parallel with the firm's 

recording.

5.2.7.2 - Refusals of Requested Information

Should management refuse to provide any reasonable 

request for information, which is not specifically required by 

the law, determine the reasons for the denial and report the 

details in the EIR. Types of refusals of interest to FDA and 

refusal codes to be entered in FACTS are listed in the FDA 

Data Codes Manual. Refusal codes' data are used when 

reporting to Congress. See IOM 5.2.5.4 for instructions in 

dealing with hostile and/or uncooperative interviewees.

5.2.8 - CONSUMER COMPLAINTS

Prior to conducting any inspection, you should review the 

FACTS system, OSAR 360, and the factory jacket 

becoming familiar with all FDA Complaint/Injury forms. You 

may want to request additional information to consumer 

compliant coordinator based on the program area to fulfill 

additional information if available related to establishment 

to be inspected. Be especially alert for ones marked 

"Surveillance Information for Next EIR” and make sure you 

investigate these during your inspection. If reviewing

complaints in OSAR, the “more detail” link needs to be 

opened to determine if the complaint was previously 

followed up, or if it stills requires follow-up.

During the inspection, discuss these complaints with 

management without revealing the complainant's name(s). 

Determine if the firm has had similar complaints on the 

same product. Determine what action the firm has taken to 

identify the root cause of the problem and to prevent a 

recurrence in the future. See IOM 5.11.4.3.11 for reporting 

instructions.

5.2.9 - INTERVIEWING CONFIDENTIAL 

INFORMANTS

When you are faced with a situation involving sources of 

information who want to remain anonymous, please contact 

your supervisor and follow the procedures here. In addition, 

refer to IOM 5.2.1.2 regarding your personal safety. If your 

management concurs with the decision to utilize a 

confidential source, it is particularly important you take the 

necessary steps to keep the identity of the source, and any 

information which could lead to the identity, confidential. 

For purposes of this subchapter, a confidential source is a 

person who provides information that may be of assistance 

to FDA without necessarily becoming a party to the actual 

FDA investigation. If you believe the information provided 

by the source could lead to a criminal investigation, please 

contact the Office of Criminal Investigations (OCI).

5.2.9.1 - How to handle the first contact

When you interview a person, who may become a 

confidential source use the following procedures:

1. Type of meeting. Try to schedule a personal interview 

with the person rather than a telephone interview. At a 

face-to-face interview you can assess the person's 

demeanor, body language, overall presentation, and 

truthfulness.

2. Meeting location. The place and time of the interview 

should be the choice of the person, unless there is a 

concern with personal safety. If the person's suggested 

location is unsuitable, the investigator should suggest 

the location. When you conduct the interview off FDA 

premises, notify your supervisor of your destination, 

purpose, and estimated time of return. When an off-site 

interview has been completed, check-in with your 

supervisor.

5.2.9.1.1 - INTERVIEWING 

METHODS/TECHNIQUES

It is strongly recommended you have two investigators 

conduct interviews of a confidential source. The lead 

investigator conducts the interview, while the second 

investigator takes notes and acts as a witness to the 

interview. You should:

1. Prepare carefully for the interview. The investigators 

should develop the questions they intend to ask the 

person during the interview, e.g., "establish motivation," 

and record and number the questions to be asked in 

their diaries prior to the interview. This preparation 
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assists in documenting the interview process and 

reduces the amount of note taking needed during the 

interview. The investigators also should discuss their 

interviewing strategy, and determine the method by 

which they will consult with each other during the 

interview and (during extensive interviews) share the 

interviewing and note-taking responsibilities;

2. Have the person tell the story chronologically, placing 

complex situations into logical order; and

3. If the person makes allegations, ask him or her how he 

or she knows the allegations are true.

a. How were they in a position to know?

b. Did they personally see, hear, or write about the 

information/incident?

c. Can they provide proof of the allegations?

5.2.9.1.2 - ESTABLISH MOTIVATION

At the end of the interview ask the person why he or she is 

divulging this information. This may reveal their motive(s):

1. Is the person a disgruntled current or former employee 

who harbors a grudge?

2. Is the person looking for some type of whistle-blower 

reward or notoriety?

3. Does the person just want to do the right thing?

4. Is the person involved in actual or prospective litigation 

about or related to the information?

5.2.9.1.3 - ANONYMITY

If the person is requesting anonymity, inform him or her 

FDA:

1. Will not divulge his or her identity, the occurrence of the 

interview, or the sensitive information provided to FDA if 

the information could lead to the identity of the person, 

unless FDA is required to disclose the information by 

law, e.g., the investigation leads to a hearing or trial and 

he or she is required to testify, and

2. Will try to corroborate all information provided by the 

person, minimizing the chances he or she must later 

testify. However, testifying remains a possibility.

Ask the person for names of other persons who might be 

willing to speak with you about the allegations and 

corroborate their story.

5.2.9.2 - Protect the Identity of the Source

Obtain sufficient personal information necessary to enable 

you to contact the person for follow up if needed. However, 

to maintain the confidentiality of the person, do not include 

the person's identifier information such as gender, name, 

address, and phone number in the memorandum of 

interview. You should assign the confidential source a code 

name or number and use the identifier in memoranda and 

other communications relating to the confidential source 

(see IOM 5.2.9.2.2 item 2).

5.2.9.2.1 - ACCESS

Know who is authorized by program division procedure to 

access the information and restrict access by others 

accordingly. Share the minimum amount of information 

necessary to meet the purpose of the disclosure.

5.2.9.2.2 - STORAGE REQUIREMENTS

Each program division should establish procedures, in 

addition to those listed below, to properly store confidential 

information. The following list contains information related 

to storage procedures.

1. Use security measures necessary to protect the 

confidentiality of personal information, whether it is in 

hard copy or electronic form, on FDA premises, in an 

FDA home-based computer, or in any other form. Use 

whatever means necessary and appropriate to 

physically safeguard the information, such as storing in 

a safe, or locked file cabinets, or password-coded 

computers, etc.

2. When referring to the source in any manner (orally, in 

writing, electronically, etc.), consider using code to 

identify the source. For example, use a number rather 

than the individual's name, to identify the source. 

Personal privacy information should be safeguarded to 

the extent allowed by law. Use discreet subject headers 

in the file labels as appropriate.

3. Remove personal information from a file only after you 

have noted in the file your name, date, etc. Promptly 

return that information to the file.

5.2.9.2.3 - DISCLOSURE

Do not disclose information from or about the source, 

unless the disclosure complies with the law and FDA's 

procedures. Do not share non-public information outside of 

the Freedom of Information (FOI) process, unless the 

sharing is done according to our regulations and 

procedures. Refer FOI requests to FDA’s Division of 

Freedom of Information (see item 3 below). See also IOM 

Subchapter 1.4. The following information relates to 

disclosures of information from or about a confidential 

source.

1. Make duplicates of the personal information only to the 

extent necessary for authorized disclosure (inside or 

outside of FDA). Do not leave the copy machine 

unattended.

2. Make only authorized disclosures of the information, 

regardless of the manner of disclosing (oral, written, 

etc.). Do not use mobile telephones or leave voice mails 

with the information. Avoid transmitting the non-public 

information by facsimile or e-mail.

3. If you receive a FOI request for information from or 

about a source consult with your supervisor immediately 

Disclosure to a non-FDA government official of 

information from or about a source may be disclosed 

only if permitted by law and FDA procedures, and after 

consulting your supervisor, OSPOP/DIDP and, if 

needed, OCI.

4. Immediately retrieve information from or about a source 

if inadvertently disclosed. Follow FDA’s Inadvertent 

Disclosure SOP. 
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5.2.9.2.4 - DESTRUCTION

Destroy personal information by shredding or similar means 

which physically destroys the record and/or, if the 

information is in electronic form, makes it unreadable.

After a matter has been referred to the Office of Chief 

Counsel (OCC) for litigation or enforcement action, consult 

with OCC if you are interested in contacting the source.

5.2.10 - ROUTINE BIOSECURITY 

PROCEDURES FOR VISITS TO FACILITIES 

HOUSING OR TRANSPORTING DOMESTIC 

OR WILD ANIMALS

This section is FDA's guidance when you visit any type of 

facility where any domestic or wild animals are housed or 

transported. If a firm has more restrictive controls, follow 

those in addition to the controls cited below as long as they 

do not interfere with your assignment needs. The controls 

and procedures are intended to prevent you from becoming 

a vector or carrier of animal diseases, to prevent the spread 

of animal disease, and to set a good example for stockmen, 

growers and industry servicemen. A number of chronic 

diseases, such as Johne's Disease, bovine virus diarrhea 

(BVD) and others exist in domestic animals which you can 

unknowingly spread. Any inspectional contact with herds of 

livestock (including poultry) or non-domesticated animals 

exposes you to potential claims of introducing or spreading 

disease. This could occur between sections of a single site, 

such as poultry houses, or between different sites or farms. 

The potential also exists for the introduction of disease from 

an animal processing plant, such as a slaughterhouse or 

renderer to a live animal facility. You can prevent this by 

following appropriate cleaning and disinfection steps 

between facilities. Generally, a break of 5 days or more 

between sites is sufficient to eliminate concern about 

transmission of infectious agents.

These precautions, biosecurity measures, are necessary in 

two types of situations. The first is when there is no known 

disease present and your actions are precautionary. This 

section primarily addresses those kinds of activities. The 

other situation involves known or suspected disease 

outbreaks or more notorious disease conditions such as 

salmonella in eggs, infectious Laryngotracheitis, foot and 

mouth disease, vesicular stomatitis, and blackhead which 

can be highly contagious and spread from one group of 

animals to another by movement of people and objects 

between infected and non-infected groups. In these cases, 

special precautions must be taken to make sure you are not 

an unknowing vector for the spread of disease. See IOM 

5.2.10.3.

Biosecurity on a produce farm is a set of preventive 

measures designed to protect the farm, including crops and 

livestock, from bacterial, fungal and viral diseases and 

agricultural pests. When conducting a produce safety 

inspection, you should abide by the farm’s policies. During 

the pre-inspection call and prior to entering the growing 

area, you should ask if the farm has implemented 

biosecurity practices. You should follow these animal and 

phytosanitary practices and procedures requirements.

If you will only be inspecting an office or house away from 

areas where animals are housed or kept, clean and suitable 

street attire may be sufficient. Be aware if you visit any area 

of a facility where animals have been, you should always 

sanitize, clean or change footwear and it may be necessary 

to change outerwear before visiting another animal site to 

prevent any possibility of transmission of disease.

Your vehicle may also transport infection if you drive 

through contaminated areas and may require frequent 

cleaning between sites.

5.2.10.1 - Pre-Inspection Activities

When you know you are going to visit or inspect any animal 

production or holding facility, consider contacting the State 

Veterinarian and/or the Regional APHIS office to determine 

if there are any areas in the state under quarantine or 

special measures to control animal diseases. APHIS office 

locations can be found on their website. The State 

Veterinarian will be listed under Government Listings in 

your phone book and is listed at this website. Milk 

Specialists frequently working with State counterparts in the 

Interstate Milk Shippers program should contact these 

sources at least quarterly for updates. Ask for any special 

controls or procedures they recommend. Follow any 

guidance they offer in addition to the precautions in this 

section. You should also consider pre-notification of the 

facility following guidance in IOM 5.2.1.1, PreAnnouncement, unless your assignment does not allow 

pre-notification. If you elect to pre-announce the inspection, 

in addition to the normal contact, ask to speak with the 

person at the facility responsible for their biosecurity 

measures and find out what they require of employees and 

visitors. If their requests do not interfere with your ability to 

do your job, follow their requests as we do when inspecting 

sterile manufacturing facilities.

Make sure your vehicle is clean and has been recently 

washed. Commercial car washes are adequate as long as 

you check to make sure any dirt, manure or other debris, 

which may be present from a previous site, has been 

removed. Some facilities may require additional disinfection 

of tires upon entry to the premises. Ensure tires and floor 

mats are clean. Consider designating places in your vehicle 

for storage of clean, unused supplies and dirty or used 

supplies.

In addition to your normal inspectional tools, obtain the 

following equipment and supplies from your program 

division:

1. Laundered or disposable coveralls or smocks (coveralls 

are suggested because they give better coverage). If 

you are going to visit multiple facilities in one day or trip, 

obtain sufficient quantities so you can change into clean 

or unused clothing between each site.

2. Disposable plastic gloves, rubber boots, which can be 

sanitized, and disposable shoe/boot covers. Rubber 
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boots over which you place disposable shoe/boot 

covers are preferred.

3. Reusable cloth or plastic laundry bag(s) for clothing to 

be laundered. (Disposable bags can be used.)

4. Soap, water and disposable or freshly laundered 

individual hand (or paper) towels.

5. Sanitizing solution(s) and equipment (brushes, bucket, 

tray, measuring devices, etc.) to permit you to properly 

sanitizing hands, boots, equipment and your vehicle. 

Most disinfectants will require removing organic matter 

before use and good brushes are essential to remove 

dirt from boots and other objects.

Make sure any equipment you take with you has been 

thoroughly cleaned and sanitized as necessary. Clip 

boards, briefcases, flashlights, inspectional sampling tools, 

coolers, brushes, buckets and other objects should be 

cleaned between uses as necessary and between visits to 

any suspected infected facilities. Disposable equipment 

should be used to the fullest extent possible.

Additional information for produce safety inspection staff to 

follow is in the Standardized Approach to Produce Farm 

Inspections document.

Maintain copies of any applicable Material Safety Data 

Sheets (MSDS) for disinfectants with you in your vehicle. If 

the firm's management requests information on the 

disinfectants you are using, they may read or copy these 

MSDS. Be familiar with the instructions and precautions 

concerning use of disinfectants. Any disinfectant should be 

effective against known or suspected microbiological 

agents.

In the event of a foreign animal disease, contact the USDA, 

APHIS Veterinary Services area Veterinarian in Charge for 

additional precautions and procedures to follow. (See 

5.2.10.3)

5.2.10.2 - General Inspection Procedures

Always begin each day with a clean vehicle free from any 

visible dirt or debris. During the day, take precautions to 

minimize contamination of your vehicle. If your vehicle 

becomes obviously dirty with adhering mud or manure, 

clean it before visiting another animal facility. When you 

arrive at a facility where animals are located, check to see 

if there are designated parking spots or pads for visitors. If 

so, park your vehicle there unless directed otherwise by the 

firm. If there is no guidance, park well away from all areas 

housing animals. When you arrive, inquire about or 

reconfirm any biosecurity measures the firm employs. 

Confirm your actions are suitable and follow expectations 

of the facility when this does not interfere with your 

inspection ability. Follow steps requested by the firm to 

remove contamination from vehicles, which may include 

troughs or pools of disinfectants for tires or other control 

measures. Avoid driving through manure, mud or 

wastewater at these sites.

In general, entry to animal housing or feeding areas, 

corrals, calf pens, hospital pens or special treatment 

facilities should be avoided unless the assignment requires 

their inspection or there are specific reasons requiring 

entry. If you must visit the feeding area occupied by 

livestock or birds, first determine if any groups are infected 

with disease. Arrange to visit the known non-disease areas 

first. Do not handle any animals unless official duty requires 

such contact. Before leaving the area where you parked 

your car, put on protective clothing as described and 

proceed with the purpose of your visit; sanitizing hands 

(and gloves if worn) and boots as necessary during the visit 

or inspection.

General procedures:

1. Wear rubber boots or other suitable footwear, which you 

disinfect upon arriving at the site and prior to departure. 

It is preferable to also place disposable foot coverings 

over your footwear, regardless of the type, after you 

have disinfected them. If the firm has footbaths, use 

them. Boots and footwear should be disinfected with any 

of the agents identified at the end of this subsection 

using a good brush. Clean and disinfect the brush(es) 

and bucket you use for these activities.

2. Wash your hands with soap and water. If you are visiting 

a facility where a known animal disease is present or the 

firm's biosecurity protocol requires, wear disposable 

gloves.

3. Wear disposable or freshly laundered coveralls, when 

appropriate. Some facilities may provide disposable 

coveralls and require visitors to shower in and shower 

out at their facilities. If requested by the firm and facilities 

are provided, you should follow those requests.

4. Wear appropriate head coverings, as necessary. If you 

wear a head covering, clean and disinfect between 

facilities or use disposable head coverings.

5. Minimize any materials you carry with you such as 

notebooks, flashlights, etc. to what is required. Consider 

keeping these things in clean plastic bags or containers 

between uses. Disinfect any of these types of items as 

best you can between visits to facilities or between 

different animal-housing areas.

6. If you are visiting production units with animals of 

multiple ages, always try to work from the youngest to 

the oldest.

7. Avoid direct contact with livestock or wild animals, bodily 

fluids or animal byproducts when visiting facilities.

8. Milk Specialists, Milk Safety Branch and State Training 

Team staff frequently working with State counterparts in 

the Interstate Milk Shippers program shall follow any 

biosecurity measures the firm employs, any biosecurity 

measures the State employs, and as a minimum shall 

follow the coded memoranda issued by CFSAN Milk 

Safety Branch on this subject.

Upon completing your assignment in a given animal area, 

return to the same area where you donned protective 

clothing. Remove disposable shoe/boot covers and gloves, 

if applicable, and place them in a disposable paper or 

plastic bag. Clean and sanitize boots/footwear. Remove the 

protective clothing, if applicable, by peeling it off inside out. 

(This keeps the surfaces exposed to contamination on the 

inside.) Unless the firm’s biosecurity plan prohibits removal 

of waste from their premises, all waste should be disposed 
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of by the investigator as follows: Place all disposable items 

in a disposable, nonporous bag for appropriate disposal

according to State and/or local regulations. Place reusable 

coveralls or other reusable protective clothing in a separate 

bag for disposition at the office.

Follow guidance on biosecurity provided in the applicable 

Compliance Program or "Guide to the Inspection of "** *" in 

addition to precautions in this Section.

Repeat these procedures for each separate location visited 

or inspected.

Purchase commercially available solutions for disinfecting 

objects or consult with your servicing laboratory. 

Commercial products such as Nolvosan, Efersan, One 

Stroke Environ or Virkon-S may be used as long as they 

are registered by EPA for the intended purpose. Lye or 

chlorine based cleaners and disinfectants may also be 

used.

The following formula for household bleach may be used. 

Mix 3/4 cup (6 oz) of liquid bleach (5.25%) in one gallon of 

water (128 oz). This solution will be approximately 1:20 

dilution. Formulations of household bleach, which are more 

concentrated than 5.25% are commercially available. Dilute 

accordingly to these directions. A more concentrated 1:10 

solution (1-oz bleach to 9-oz water) may be used with 

decreased contact time required. Dilutions should be 

prepared fresh daily and protected from light.

You should read the label and be familiar with directions 

and precautions, such as removing any organic matter from 

objects to be disinfected, for any disinfectant you use. In 

the absence of directions or for chlorine solutions you 

prepare: 1. Remove visible dirt from the object (boots, tools, 

tires, etc.). 2. Wipe, brush or scrub surfaces with the 

solution and keep wet for 2 minutes. 3. Allow to air dry or 

dry with previously sterilized toweling.

5.2.10.3 - Special Situation Precautions

If you are required to inspect or visit a facility known or 

suspected to be involved in a contagious animal disease an 

outbreak or otherwise identified as having diseased 

animals, contact the Center for Veterinary Medicine and/or 

Center for Food Safety and Applied Nutrition for additional 

precautions which may be necessary before you visit these 

sites. Your activities may be limited to visiting a single site 

in a day, taking extra-ordinary decontamination steps, 

ensuring you do not visit or inspect another facility for 5 or 

more days following the visit to the contaminated site or 

other steps. APHIS may have special restrictions or 

precautions for you to follow. The State Veterinarian may 

also request you follow additional requirements. During 

inspections of poultry operations where salmonella 

contamination is known or suspected, you should make 

sure you contact CFSAN directly for specific procedures to 

follow. Additional decontamination steps will be required.

5.2.10.3 – Standard Operating Biosecurity 

Procedures for Egg Farm Inspections/ 

commercial Poultry Operations

Classification of Farms

Program divisions should categorize inspections 

according to risk with farms providing out-door access 

being considered the highest risk to HPAI. Large farms 

(those with ≥ 50,000 layers should be inspected first, 

followed by small farms (those with between 3,000-49,999 

layers) and farms with outdoor access (regardless of the 

number of birds at the farm) should be inspected last. For 

example, if a program division is assigned 15 inspections 

as part of an Egg Assignment, and 5 of those firms 

provide outdoor access, the 10 farms that do not provide 

outdoor access should be inspected first and the 5 with 

outdoor access should be inspected last. Of the first 10 of 

these inspections the largest farms (from a number of 

layers at the farm perspective) should be inspected first 

and then in descending order as the number of layers 

decreases (a farm with 1 million layers would be inspected 

before a farm with 750,000 layers, even though both are 

classified as large farms).

Biosecurity Practices

These practices should be followed on every egg farm 

inspection. It is the responsibility of the lead investigator to 

brief his/her inspectional team on these practices prior to 

arrival at the farm.

Pre-Inspection Measures

1. Contact the State Veterinarian to check for quarantines. 

No egg inspections should be initiated without first 

contacting the state veterinary office and checking for 

quarantines. Investigators should ask if there is any type 

of quarantine and follow that up with a question 

specifically about HPAI-related quarantines. If quarantines 

are in place, investigators should ask how long they are 

expected to continue. If the state veterinarian or official 

designated by the state indicates that inspections should 

not continue, those instructions should be followed, and 

no inspections should be conducted until state clearance 

is given. If an extended quarantine is expected (longer 

than 2 weeks), the program division should organize a 

follow up meeting to include the program division, State 

Veterinary Office or designated state official, ORA-OFFO, 

CFSAN-OFS, and CFSAN-OC (see contacts at the end of 

this document). The purpose of these meetings will be to 

establish a channel of communication between FDA and 

the State to ensure state concerns are addressed while 

ensuring FDA’s inspectional obligations are met.

2. Following clearance from the state veterinarian’s office, 

the lead investigator should conduct a cross reference 

check of the inspection location against the HPAI Current 

Avian Influenza findings on the USDA/APHIS web page. 

The Current Avian Influenza findings can be found at the 

following web address:
CHAPTER 5 INVESTIGATIONS OPERATIONS MANUAL 2023 

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https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/n

vap/NVAP-Reference-Guide/Poultry/Avian-Influenza

During the cross check, investigators should check the 

state and county from the USDA/APHIS webpage against 

the location of the farm to be inspected. If the farm is in 

the same county as a confirmed HPAI occurrence, the 

program division should cancel the inspection and set up 

a follow up meeting to include the program division, ORAOFFO, CFSAN-OC and CFSAN-OFS (see contacts at the 

end of this document). During this meeting, the following 

information will be considered: the confirmation date of the 

occurrence (how far removed from the time HPAI was 

detected to when the current inspection is scheduled), the 

relative locations of the HPAI infected site and the farm to 

be inspected (the infected, buffer, and surveillance zone 

criteria established by APHIS will be considered), and 

other pertinent information. After all pertinent information 

is considered, a decision will be made to either cancel the 

inspection or reschedule it for a more appropriate time.

3.The mandatory minimum wait time between different 

farms is 72 hrs. However, many farms have increased the 

wait period to longer than 72 hrs. in response to lessons 

learned from the 2015 HPAI outbreak. If the wait time 

established by the producer is longer than 72 hrs., that 

specified wait time should be adhered to. In situations 

where the farm to be inspected includes outdoor access 

for the birds (this information should be established during 

the pre-inspection call) the minimum wait time between 

farms increases to 1 week. Contact with specific bird 

populations could also result into mandatory one week 

minimum wait times. Bird populations should be 

categorized into two broad categories. Population 1 

includes birds that are under a biosecurity plan as 

specified in 21 CFR 110 118.4(b)(1) through (5) (this 

populations most often will refer to only those birds at 

commercial farms, i.e. those to be inspected). Population 

2 includes all other birds, including but not limited to 

backyard flocks, duck or geese or other bird populations at 

municipal parks, avian species at zoological gardens, 

chicks or ducklings at feed stores, etc. If an investigator 

only has contact with Population 1 AND if the farm to be 

inspected has an established wait time of less than 1 

week, that time requirement should be followed. If an 

investigator has contact with Population 2, they MUST 

wait 1 week before conducting an inspection.

4. When possible, program divisions should send separate 

inspectional teams on egg farm inspections such that the 

time between separate farm visits for any one inspectional 

team is maximized. For example, rather than sending 

Inspectional Team A to conduct inspections at Farm 1, 

Farm 2 and Farm 3, every attempt should be made to 

instead send Inspectional Team A to conduct the 

inspection at Farm 1, Inspectional Team B to conduct the 

inspection at Farm 2 and Inspectional

Team C to conduct the inspection at Farm 3. The goal 

being to increase the length of time that any of the three 

inspectional teams have to visit the next farm up for 

inspection.

5. Vehicles to be used during inspections should be 

washed a maximum of 24 hours before and after each egg 

inspection. Given that HPAI is highly susceptible to 

detergents, high temperatures and desiccation, cars 

washes where hand held nozzles are available should be 

used when possible. Initially, a cycle should be conducted 

where a high-pressure rinse is used to remove all organic 

matter (e.g. mud, dirt and debris) with specific care taken 

to address the wheel wells, tires, vehicle undercarriage, 

and vehicle body. This should be followed by a cycle 

where a scrub brush with a detergent is used on the whole 

vehicle including the wheel wells, tires, and vehicle body. 

Subsequently, a high-pressure rinse that includes the 

wheel wells, tires, vehicle undercarriage and vehicle body 

should be completed. The interior of the vehicle should 

then be vacuumed thoroughly to remove organic matter 

and floor mats sprayed with a disinfectant aerosol spray. 

The vehicle should then be allowed to dry thoroughly in a 

sunny area (as opposed to a shaded garage). After the 

vehicle has dried, disinfectant should be applied to the 

wheel wells, tires and undercarriage (See item #11 below 

for appropriate disinfectant selection). The vehicle body 

does not have to be disinfected.

When necessary or during inclement weather, drivethrough car washes may be substituted for manual car 

washes provided that the cycle includes an undercarriage 

wash, application of a detergent and a high-pressure

rinse. The interior should still be vacuumed and 

disinfected following the car wash. After the vehicle dries, 

the tires, wheel wells and undercarriage should be 

disinfected as described above.

During-Inspection Measures

6.Follow the farm’s own biosecurity program to the extent 

that it does not interfere with investigators conducting the 

inspection.

7.Do not enter or inspect houses where birds are known to 

have disease, including but not limited to, SE.

8.FDA personnel participating in the inspection cannot be 

bird owners. Ownership of birds disqualifies that 

investigator from participation in all egg farm inspections.

9.Always change all Personal Protective Equipment (PPE) 

between houses. PPE includes disposable body 

coverings, boot covers, hair bonnets, sterile gloves, 

respirators, eye and hearing (in areas where loud 

machinery is in use) protection. The use of disposable 

PPE and respirators is preferred to eliminate the need for 

disinfection between poultry houses. In situations where 

permanent eyewear is worn it must be cleaned and 

disinfected between each poultry house.

10. Investigators should wash hands thoroughly before 

donning gloves for entry into the house. Where available, 

use soap and water; if not available, use hand sanitizing 
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gels. It is the responsibility of the team lead to ensure that 

all members of the team are adhering to protocol. This 

should be done at both the clean and dirty areas 

established at the farm, prior to entry into any poultry 

house.

11. Selection of disinfectants:

Ethanol should be used to disinfect the lids of evaporated 

milk cans, scissors and can openers used during sampling 

within a poultry house.

Phenolic or quaternary ammonium-based sanitizers 

should be used on wheel wells, tires and vehicle under 

carriage. The vehicle body should not be disinfected, as 

the detergent from the car wash is sufficient and some 

sanitizing compounds can damage the vehicles finish.

Lysol or equivalent based aerosol spray should be used 

on floor mats and soles of shoes.

Purell or equivalent hand gel should be used for hand 

disinfection.

In situations where reusable respirators are used they 

must be cleaned and disinfected in accordance with 

manufacturer’s recommendations

Selection of the appropriate disinfectant is critical; for 

questions or assistance with disinfectant selection please 

contact ORA-OO-ORS (see contacts at the end of this 

document).

12.No item which has been in a layer house may be 

brought into a different house without a complete cleaning 

and disinfection or replacement with a new one. This 

includes all items, e.g., pens, supply tubs, scissors. 

Replacement of items is more effective than disinfection 

and lessens the workload on site; therefore, all efforts 

should be made to replace items rather than transfer 

between houses. Investigators should plan carefully prior 

to inspections and pack inspection kits on a per house 

basis so as to eliminate the need to share equipment 

between houses. Aside from permanent eyewear and 

“egg pad” tablets, there should not be a need to share 

equipment/items between houses.

13.Use disposable cameras, when possible. Otherwise, 

digital cameras are to be placed within plastic bags prior 

to entry into the house.

14.Double bag all garbage; specifically, one bag is to be 

left at the vehicle and the other taken into the house to be 

inspected. When the garbage is removed, it is placed into 

the bag left at the vehicle, so as to assure that the bag 

which went into the layer house never touches the vehicle 

interior.

15.Houses should be inspected from the cleanest areas to 

the dirtiest areas and from the youngest to oldest birds.

16.No jewelry is allowed to be worn into poultry houses.

17.Where possible, wear clothing that has not been on 

another egg farm and ensure the clothing is laundered. If 

possible use the hot water cycle to launder clothing that 

will be used during an egg inspection.

18.If possible, inspectors should park their car at the 

beginning of the driveway or outside the farm and carry all 

of their equipment onto the farm. Investigators should 

coordinate with farm management to determine the best 

parking spot for the vehicle.

19.Eyeglasses should be cleaned and disinfected with 

disposable decontamination wipes.

Items 20-32 listed below represent either direct or indirect 

contact with Population 2 as described in item #3 of the 

pre-inspection measures above. A minimum of 1 week, 

preferably longer, prior to participating in an FDA egg farm 

inspection, all investigators involved in the inspections 

should:

20.Not come in contact with bird feeders or bird baths for 

a minimum of 1 week prior to participating in an egg farm 

inspection.

21.Stay away from family members, friends or 

acquaintances that are pet bird owners or have backyard 

poultry flocks of any type.

22.Not visit fairs where poultry or birds are shown or 

exhibited.

23.Not visit live bird markets of any type, or gatherings 

where live birds may be present.

24.Not visit flea markets, trade shows, or swap meets 

where live poultry or birds of any type may be present.

25.Not visit zoos, theme or amusement parks where live 

birds maybe present.

26.Not visit known nesting grounds or resting place for 

wild birds, such as natural preserves or refuges, known 

breeding grounds or bird sanctuaries.

27.Not attend birthday parties or functions where a petting 

zoo that includes poultry is part of the event, e.g., baby 

chicks, pet ducks or geese, are present.

28.Not come in contact with birds, such as ducks or 

geese, at municipal, state or other types of parks. e.g., 

where ducks, geese or pigeons and other birds are local 

inhabitants and people congregate to feed them.

29.Not visit an ocean side town where you may come in 

contact with shorebirds, e.g., gulls.

30.Not visit feed stores or other retail establishments 

where live poultry may be sold, e.g., baby chicks, turkey 

poults, ducklings, etc.

31.Not go hunting for wild fowl or handle wild fowl. If you 

have family members or friends who hunt fowl, do not 

come in contact with them for a least the week prior to the 

inspection.
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32. Not meet with other known bird owners either as part 

of your work (e.g., meeting another producer at a location 

away from their farm) or meet with other known bird 

owners in your social circle.

Post-Inspection Measures

33.Wash the vehicle used during the inspection as 

specified in item #5 in the pre-inspection procedures of 

this directive.

34.Clean and disinfect the sampling kit(s), e.g. tubs, 

scissors, can openers

35. Clean and disinfect respirators in accordance with 

manufacturer’s recommendations

Contacts

CFSAN-OC:

Doriliz De Leon, email: doriliz.deleon@fda.hhs.gov, 

phone: 240-402-2772

Robyn Jones, email: robyn.jones@fda.hhs.gov, phone: 

240-402-2575

CFSAN-OFS

John Sheehan, email: john.sheehan@fda.hhs.gov, phone: 

240-402-1488

Gerardo A Ramirez, email: gerardo.ramirez@fda.hhs.gov, 

phone: 713-293-1418

ORA-DDHAFO/HAFPOB

Martha Myrick, email: martha.myrick@fda.hhs.gov, phone: 

616-304-6283

ORA-ORS

Michelle Markley, email: michelle.markley@fda.hhs.gov, 

phone: 301-796-8178

Kenneth Crombie, email: Kenneth.crombie@fda.hhs.gov, 

phone: 240-402-5346

SUBCHAPTER 5.3 - EVIDENCE 

DEVELOPMENT

5.3.1 - TECHNIQUES

The recognition, collection, and effective presentation of 

admissible evidence is essential to successful litigation. 

Evidence is required to support your observations and 

reports of violative conditions.

Although the inspectional procedures to detect adulteration 

and contamination, etc., are described under specific 

headings in the IOM, the same procedures and/or 

techniques may also apply to other areas. For instance, the 

procedures to detect contamination from filth, insects, 

rodents, birds, etc., described in IOM section 5.4.7 may 

also apply to drugs or other products. Your experience and 

training assists you in making this transition and enables 

you to detect possible violative conditions.

Keep in mind the policy annunciated in the 4/23/1991 

memorandum from the Director, Office of Compliance: The 

lack of a violative physical sample is not a bar to pursuing 

regulatory and/or administrative action providing the CGMP 

deficiencies have been well documented. Likewise, 

physical samples found to be in compliance are not a bar 

to pursuing action under CGMP charges.

5.3.2 -SAMPLES

Samples, including “Factory Food Samples” (in-lines) and 

packaged finished products collected during inspections 

provide the necessary key to establish routes of 

contamination and/or actual product adulteration. They also 

document the character of products packed prior to the 

inspection. Collect samples for laboratory examination only 

when they contribute to confirming the suspected violation. 

Be selective since negative reports of analysis of food 

samples are required under Section 704(d) of the FD&C Act

[21 U.S.C. 374 (d)] to be furnished to the firm and might 

give management a false picture of the firm's operation.

When possible collect duplicate subsamples to provide for 

the 702(b) portion of the sample. See IOM 4.3.1.1 and 

4.3.7.4.1 for additional guidance and 21 CFR 2.10 for 

exemptions regarding the collection of duplicate portions.

When shipping samples collected during a foreign 

establishment inspection or during FDA activities in a U.S. 

territory outside of the Customs territory of the United 

States (e.g., Guam, American Samoa, etc.), refer to IOM 

section 4.3.4.6 for notification procedures.

https://www.ecfr.gov/current/title-19/chapterI/part-7/section-7.2

5.3.3 - EXHIBITS

Impressive exhibits are extremely effective and important 

forms of evidence to establish existence of violative 

conditions or products. They should relate to insanitary 

conditions contributing or likely to contribute, filth to the 

finished product, or to practices likely to render the product 

injurious or otherwise violative. Diagrams of the 

establishment, floor plans, flow charts, and schematics are 

useful in preparing a clear concise report and in later 

presentation of testimony. A small compass is useful in 

describing exact locations of objectionable conditions in the 

plant, in your diagrams, and locations from which samples 

were taken, etc. 

Submit as an INV sample exhibits (except photographs) 

collected during an inspection or investigation. Describe 

each subsample and assign a unique subsample number 

to each exhibit. Group similar subsamples on one 

collection report. Examples of exhibits include:

1. Live and dead insects, insect frass, webbing, and 

insect chewed materials; nesting material of rodents 

and/or other animals; and other behavioral evidence of 

the presence of insects, rodents and other animals. 

(“INV Samples of Filth Exhibits.)
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2. Components and finished dosage forms.

3. Samples of in-process ingredients, in-process materials 

and unpackaged finished products. (“Factory Food 

Samples” or “in-lines.”) Note: Samples of packaged 

finished products and ingredients are official samples.

4. Manufacturing and control devices or aids.

5. Physical samples if possible and practical or, 

photographs with descriptions of scoops, stop-gap 

expediencies, other unorthodox manufacturing 

equipment or makeshift procedures. If photos are taken, 

follow the procedures described in IOM 5.3.4.

6. Evidence showing the presence of prohibited pesticide 

residues. A method of swabbing for prohibited pesticide 

residues was published in Laboratory Information 

Bulletin # 1622. Excerpts are quoted as follows:

a. Apparatus - Four dram size glass vials, 95% ethanol, 

and cotton swabs preformed on 6" long wooden 

handles. Keep uncontaminated in a clean plastic 

bag.

b. Procedure - Blow away loose dirt or debris from 

approximately a 3" x 3" selected area. Measure 

approximately 2 cm of 95% ethanol in vial, dip swab 

into ethanol, press out excess on inside of vial and 

roll moist swab back and forth firmly across the 

selected area. Return swab to vial, swirl in alcohol, 

press out excess on inside of vial and again roll moist 

swab across the same area 90° to the previous 

swabbing. Re-insert swab into vial, break off swab 

handle and cap the vial with the swab inside.

c. When swab subsamples are submitted, also submit 

a blank control sub consisting of an unused swab 

placed in a capped vial containing 2 cm of the same 

alcohol that was used for the other swabs.

d. Describe the type of material swabbed (cardboard 

carton, metal table top, rubber inspection belt, etc.) 

and the area covered. A reasonable area is 

approximately 10 sq. inches. Always try to establish 

a definite link in the chain of subsamples leading 

towards the highest level of contamination. If 

possible, identify the pesticide suspected. Be sure to 

include a floor plan with the areas sampled identified.

Do not remove the firm's only copy of records. Whenever 

possible, scan, photograph or photocopy, if duplicates are 

not available. Reproductions should be reviewed to ensure 

all relevant information is readable. Records should not be 

accepted by email from outside USFDA.

5.3.4 - PHOTOGRAPHS

Photos taken during inspections are not investigational 

samples. They are exhibits. Photos are not attached to 

collection reports unless the photos are part of an Official 

Sample. See IOM 4.1.4 Official Samples and IOM 4.7.2.4

Photographs. Only use a Government issued camera to 

take photographs.

Since photographs are one of the most effective and useful 

forms of evidence, every photo should be taken with a 

purpose. Photographs should only be taken for evidentiary 

purposes, e.g., to document violations and environmental 

surface subsample sites. Photographs should be related to 

insanitary conditions contributing or likely to contribute filth 

to the finished product, or to practices likely to render it 

injurious or otherwise violative.

CAUTION: Evaluate the area where flash photography is 

contemplated. Do not use flash where there is a potentially 

explosive condition; e.g. very dusty areas or possible 

presence of explosive or flammable vapors. In these 

situations, use extremely fast film and/or long exposure 

time instead of flash.

Examples of conditions or practices effectively documented 

by photographs include:

1. Evidence of rodents or insect infestation and faulty 

construction or maintenance, which contributes to these 

conditions.

2. Routes of, as well as, actual contamination of raw 

materials or finished products.

3. Condition of raw materials or finished products.

4. Employee practices contributing to contamination or to 

violative conditions.

5. Manufacturing processes.

6. Manufacturing and various control records showing 

errors, substitutions, penciled changes in procedure, 

faulty practices, deviations from GMP's, NDA's, or other 

protocols, altered or inadequate assays or other control 

procedures and any variation from stated procedure. 

See IOM 5.3.8.2 for identification of records.

7. Effluent contamination of water systems. See IOM 5.4.3 

for techniques in photographing this type of 

contamination.

When photographing labels, make sure your picture will 

result in a legible label with printing large enough to be read 

by an unaided eye. Photograph whited out documents by 

holding a flashlight against the whited outer side and taking 

a close-up photo of the reverse using high-speed film. This 

will produce a photo with a mirror image of the whited outer

side.

If you use a Polaroid camera or color slide film, explain the 

facts in your EIR or on the C/R to alert reviewers that there 

are no negatives.

5.3.4.1 - In-Firm Photographs

Take your camera into the firm and use it as necessary just 

as you use other inspectional equipment. Only FDA issued 

cameras are to be used in official business. Don’t request 

permission from firm management to take photographs 

during an inspection because taking photographs is part of 

the Agency’s authority to conduct inspections as part of 

Section 704(a)(1) of the FD&C Act [21 USC 374(a)(1)].

If management objects to taking photographs, explain that 

photos are an integral part of an inspection and present an 

accurate picture of firm conditions. Advise management 

the U. S. Courts have held that photographs may lawfully 

be taken as part of an inspection. If management continues 

to refuse, provide them with the following references:
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1. "Dow Chemical v. United States”, 476 U.S. 227 (1986) 

This Supreme Court Decision dealt with aerial 

photographs by EPA, but the Court's language seems 

to address the right to take photographs by any 

regulatory agency. The decision reads in part, "** When 

Congress invests an agency with enforcement and 

investigatory authority, it is not necessary to identify 

explicitly each and every technique that may be used in 

the course of executing the statutory mission. ***"

2. "United States of America v. Acri Wholesale Grocery 

Company, A Corporation, and JOSEPH D. ACRI and 

ANTHONY ACRI, Individuals", U.S. Division Court for 

Southern Division of Iowa. 409 F. Supp. 529. Decided 

February 24, 1976.

If management refuses, obtain name and contact 

information for the firm’s legal counsel, and advise your 

program division management immediately. If the firm does 

not have legal counsel on retainer, collect the name and 

contact information for the most responsible individual. 

Program division management will inform their ORA 

Regional Counselor in the Office of Chief Counsel (OCC) 

of the situation, and OCC will then contact the firm’s legal 

counsel or most responsible individual to discuss FDA’s 

legal right to take pictures during inspections. OCC will 

relay the results of this conversation to program division

management. If you have already taken some photos do 

not surrender film to management. Advise the firm it can 

obtain copies of the photos under the Freedom of 

Information Act. See IOM 5.3.4.5.

If management of a drug or device firm does not give a 

reasonable explanation for its objection, such as a showing 

that the chemical properties of products manufactured at 

the facility are such that taking photographs would 

adversely affect product quality, you may advise 

management that the refusal may constitute a limiting of the 

inspection under Section 501(j) [21 U.S.C. 551(j)] of the 

FD&C.

5.3.4.2 - Photo Identification and Submission

One of the most critical aspects about photographs or 

videotapes is the ability for the agency to provide testimony 

clearly verifying the authenticity of the conditions depicted 

in the photograph or video. It makes no difference if the 

photo is a 35 mm print from acetate negatives, a Polaroid 

photo, a digital photo or video taken with a video recorder. 

You must create a trail, starting with the taking of the photo, 

confirming its original accuracy and establishing a record 

describing the chain of custody. To do this, you must make 

sure each photograph is described in your regulatory notes 

in sufficient detail to assure positive correlation of the photo 

or video with your inspection findings. One way you can do 

this is to photograph a card with your name, program 

division address and phone number as the first frame or 

picture on a roll of film or in the digital record. This will help 

identify the film or file and assist in tracking if it is lost or 

becomes separated from its identification envelope during 

processing or storage. Proper procedures will also allow the 

agency to provide evidence confirming the authenticity of 

the photographs or video recording in the event you are not 

able to testify personally.

5.3.4.2.1 – FILM BASED PRINTS

Identify each print on the margin with exhibit number, firm 

name (or DOC Sample Nos., if DOC Sample), date taken 

or inclusive dates of inspection, and your initials. Do not 

place any identifying marks on the picture area of the print. 

(Some photo developing firms are supplying borderless 

prints. For this type print, place identification along the back 

bottom edge of the print and mount the print so the 

identification can be read without removing the print from 

the mounting paper. A narrative description may be placed 

on the mounting paper next to the print. If part of an EIR, 

include as exhibits. If part of a DOC sample, attach to the 

collection report with other records associated with a DOC 

Sample.)

5.3.4.2.2 - COLOR SLIDE IDENTIFICATION

If color slides are used, identify each slide, in the same 

manner as for prints. Program divisions may have special 

mounting frames for color slides, so the narrative 

description of each slide must be in the body of the report 

with proper reference to exhibits, or, each description may 

be placed on sheets of paper following the mounting frames 

and properly referenced.

5.3.4.2.3 - NEGATIVE IDENTIFICATION

Identify the edge of at least two negative strips, with the 

same information as for prints using a 3/16" strip of 

pressure sensitive tape. Place all negatives in an FDA-525 

envelope. Complete blocks 2, 3, (4 if DOC Sample), 5, 7, 

and 12 and seal with an Official Seal, FDA-415a. If 

negatives are not part of a DOC Sample, enter firm name 

in the Sample Number block.

As applicable, submit the sealed FDA-525 or envelope as 

an exhibit to the EIR, with the Investigative Report as an 

attachment, or with the other associated 

records/documents with a DOC Sample.

5.3.4.2.4 - VIDEO RECORDINGS

Handle and protect the original video record just as if it were 

a photograph negative. Unused videotapes should 

generally be used to capture the video and, for subsequent 

copies of the original recording. Write-protect and identify 

the original videotape with a label with the firm name (or 

Sample number if it is being submitted as part of an official 

sample), date taken, and your initials. Seal the original copy 

of the electronic media in an FDA-525 or similar envelope. 

Complete blocks 2, 3, 5, 7, and 12 of the FDA 525 and seal 

with an Official Seal, FDA-415a. If you use a larger 

envelope, identify the envelope with your name, title, home 

program division, date, firm name, firm address (include zip 

code), and description of the contents of the envelope.
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Seal the original videotape in an FDA-525 envelope or 

similar envelope. If you use a larger envelope, identify the 

envelope with your name, title, home program division, 

date, firm name, firm address (include zip code), 

description of the contents of the envelope, and marked in 

large, bolded letters "STORE AWAY AND PROTECT 

FROM MAGNETIC FIELDS."

As applicable, submit the sealed FDA-525 or similar 

envelope as an exhibit to the EIR, with the Investigation 

Memorandum as an attachment, or with the other 

associated records and documents with a DOC sample.

If you perform any editing of the recording, you should only 

perform this on a copy of the original video recording to 

prevent possible damage to the original. Document in your 

regulatory notes you made a copy of the original and 

verified the copy is an accurate copy of the original video 

you took. This "original copy" should be treated just as if it 

is the original. When you sign the report, memorandum or 

other agency document, your signature certifies you are 

saying the content of the document, including any video 

recordings, is true and accurate to the best of your ability

5.3.4.2.5 – DIGITAL PHOTOGRAPHS OR 

VIDEO RECORDINGS

Prior to the year 2000, FDA investigators traditionally 

worked with silver acetate photographic film or used analog 

video tapes. Early digital cameras recorded photographic 

images directly to floppy disks or mini-CDs in which the 

evidence could be handled like photographic negatives.

The important difference today is digital cameras are 

capable of recording high resolution images on the order of 

twenty to thirty megapixels. The corresponding image file 

sizes can be over fifteen megabytes when using 

uncompressed file formats. To cope with the increased file 

sizes, digital camera manufacturers have introduced nonvolatile flash memory cards which can record digital 

images, delete images, and be recorded over and over 

again. This presents a new issue since the original digital 

images, which are captured at the moment when the 

images are recorded on the memory card, will be copied at 

a later time to a CD-R or other permanent storage media. 

Due to the cost of flash memory cards and the large file 

sizes, it is not feasible to purchase new memory cards for 

each inspection/investigation as you did using 

photographic film. You will be working with an “original 

copy” of the images which have to be copied in the exact 

format to a CD-R or DVD-R as they were originally recorded 

on the flash memory card to preserve the chain of custody.

The term “other permanent storage media” includes the 

hard-drive on the work computer/laptop of the investigator, 

and not a shared or personal computer. In order to preserve 

the chain of custody, it is acceptable to transfer the images 

from the flash memory card onto the hard-drive and then 

burn the images onto a CD-R or DVD-R, so long as the 

images have not been altered in any way before being 

burned onto the CD-R or DVD-R.

In the same manner, digital video recordings may involve 

the use of different media types such as tapes, CD-Rs or 

DVD-Rs, or built-in hard drives. If you cannot handle the 

original video recording as in IOM 5.3.4.2.4, you will need 

to create an “original copy” of the video recording.

Despite the differences in photographic film and digital 

technology, you are responsible for collection, handling, 

documenting the chain of custody, storage, and submission 

of your evidence in a manner where you can testify to its 

authenticity in a court of law. See IOM 5.3.4.2 and 5.3.4.3.

5.3.4.2.6 – GLOSSARY OF DIGITAL 

TERMINOLOGY

Some basic terminology is used when referring to digital 

devices in IOM 5.3.4.2.4, 5.3.4.2.5, 5.3.4.3.

5.3.4.2.6.1 – Digital Data

Electronic data in binary form consisting in its simplest form 

as “1”s and “0”s. A computer interprets data by whether the 

state is on (“1”) or off (“0”).

5.3.4.2.6.2 – Analog Data

Information captured in a directly measurable signal versus 

an analog signal converted and stored in binary.

5.3.4.2.6.3 – Memory Card

Any non-volatile memory media that can be removed and 

which retains data without the need for electrical power.

Examples of current memory cards are: Compact Flash 

(CF), Secure Digital (SD), Memory Stick (Sony), and 

Extreme Digital (xD).

5.3.4.2.6.4 - Original

The file recorded by a digital device on digital storage 

media at the moment in time when the user takes a picture 

or makes a recording. This concept is similar to a film 

camera where the photographic film records the image 

when exposed by light. The film image negatives produced 

when the film is developed are considered the originals and 

prints are considered copies. See IOM 5.3.4.2.1 and 

5.3.4.2.3.

5.3.4.2.6.5 – Original Copy

An exact copy of the original file recorded by the digital 

device (camera, video recorder, etc.). The original copy will 

retain all the characteristics of the original and is 

indistinguishable from the original.

5.3.4.2.6.6 - Permanent Storage Media

A media format in which the digital files cannot be altered 

once written. Examples are CD-Rs, DVD-Rs and other 

approved media.
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5.3.4.2.6.7 - Time/Date Stamp

The internal clock within the camera which records the 

time/date information on the image file. Set the time/date 

stamp for the location where the photographs or videos are 

being taken. In this usage, the time/date stamp does not 

refer to imprinting the time/date stamp within the 

photographic image although the time/date stamp can also 

be imprinted on the photograph as some film cameras 

could do.

5.3.4.2.6.8 - Working Copy

A copy of the original copy used when you need to make 

additional copies for your report, sample C/R. Creating a 

working copy decreases the chance the original copy is 

damaged.

5.3.4.3 - Preparing and Maintaining Digital 

Photographs as Regulatory Evidence

Assure and protect a digital photo's chain of custody (and 

authenticity) following this procedure:

1. Prior to using the digital camera, verify the date and time 

stamp is correct and there are no images stored on the 

memory card. Reformat the memory card using your 

camera’s reformat command to delete any images not 

related to your current assignment. Depending on your 

inspection/investigation, camera, and memory card 

capacity you should consider bringing more than one 

memory card if possible.

2. Handle your camera and the memory cards in a manner 

to protect your evidence and maintain the trail of the 

"chain of custody" for the evidence you have collected. 

For example, keep the camera and memory cards in 

your personal possession at all times or hold under lock

and key in a secure storage area. Also, keep any 

additional memory cards containing images in your 

personal possession until transferred to permanent 

storage media. When necessary, document these facts 

in your regulatory notes or written report (EIR, CR etc.).

3. As soon as practical, create an original copy of the 

digital photos. Some older FDA cameras will capture 

images directly to a (Write-once Compact Disk 

Recordable (CD-R)); in this case, the CD-R from these 

cameras becomes the original CD-R. Identify, date and 

initial the CD-R as an original image record. If a CD-R/W 

was used, copy the images to a CD-R to create an 

original copy with files that cannot be altered. Follow 

additional instructions for creating and finishing a CD-R 

in step 4 below.

4. If the camera requires downloading of images to a CDR or other media, download all the images from the 

digital camera to an unused CD-R or other electronic 

storage media to create an original copy. If there was 

more than one memory card used, use a separate CDR for each memory card. The storage capacity of a CDR is about 650 MB; thus, more than one CD-R may be 

needed to create an original copy of your memory card 

depending on your camera's resolution, the storage 

capacity of your memory card, and the number of 

pictures taken. The images should be transferred in a 

file format maintaining the image resolution at the time 

the image was captured. If possible, avoid the use of 

any file compression in transferring the images to the 

CD-R. Prior to preparing the CD-R or transferring image 

files, verify that the computer you are using is set to the 

correct date and time. Make the CD-R permanent in a 

format readable by any CD-R reader. Prior to making 

the working copy from the original copy, identify the 

original copy. For EIRs identify with the firm name, FEI, 

date taken or inclusive dates of inspection, and your 

initials. For sample collections identify with sample 

number, collection date, and your initials It is important 

to identify the original copy as soon as possible to 

prevent possible mix up of the original copy with any 

working copies.

5. Use a permanent CD safe marker to identify the original 

copy CD-R. Do not use ball point pens or similar tipped 

markers since the CD-R may be damaged. See the

NIST document, “Care and Handling of CDs and DVDs 

- A Guide for Librarians and Archivists”. Figure 12, page 

23 shows where to identify the CD-R.

6. Where applicable, document in your regulatory notes

the verification and identification of each photographic 

image comparing them to your regulatory notes, which 

were recorded at the time the photographs were taken.

7. 

Make only one working copy from each original copy. 

Make any additional working copies using the initial 

working copy. No more than one copy should be made 

from the original copy to preserve the original copy. 

After making the initial working copy, seal the original 

copy of the electronic media in an FDA-525 or similar 

envelope until submitted with the written report (e.g., 

EIR, C/R.). Complete blocks 2, 3, 5, 7, and 12 of the 

FDA 525 and seal with an Official Seal, FDA-415a. If 

you use a larger envelope, identify the envelope with 

your name, title, home program division, date, firm 

name, firm address (include zip code), description of the 

contents of the envelope and seal with an Official Seal, 

FDA- 415a. If the images are captured or transferred to 

electronic storage media, refer to IOM 5.3.8.3 for the 

handling of electronic storage media. If possible, the 

investigator (who took the photos and will authenticate 

them at trial) should store the sealed electronic storage 

media until it is submitted with the written report. If 

you break the seal for any reason, see IOM 4.7.4.5 – 

Broken Official Seals and “Temporary Seals.”

8. Working copies should be used to print photos, insertion 

into an EIR, cropped, otherwise edited or to be included 

in a referral.

9. Document in your regulatory notes or written report 

(EIR, CR, etc.) any steps taken for any unusual editing

of original photo images. For example: Superimposing 

over an important area of the image, image 

enhancement, composite images, etc.

10.Do not scan the FDA 525 or envelopes containing the 

photo discs and upload as exhibits. The actual 
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photographs included and described in the EIR are the 

official exhibit and are maintained in the eNSpect 

system. The original officially sealed disc(s) and 

unsealed working copy disc(s) should be included with 

the unlabeled hard copy exhibits and attachments filed 

in accordance with applicable procedures. The 

following statement should be included section 

5.11.4.3.16 - Additional Information, “The officially

sealed original copy and unsealed working copy discs 

containing the photographs taken during the inspection 

are filed with the unlabeled exhibits and attachments.”

5.3.4.4 - Preparing Digital Photos for 

Insertion in an eNSpect Establishment 

Inspection Report (EIR)

Digital photos taken during an inspection can be inserted 

into the body of a report in eNSpect or can be printed and 

attached to the EIR as an exhibit. Inserting digital photos 

can dramatically increase the file size of the eNSpect

document. To maintain a minimum eNSpect document file 

size, the following is recommended: Do not open a digital 

picture/photo and use copy and paste to insert the 

picture/photo into the eNSpect document. Instead, save 

pictures/photos in a JPEG image format (.jpg file name 

extension) in a separate folder in preparation for inserting 

into eNSpect. Then resize all the JPEG pictures to a 

reasonable image file size. Ensure you are not using the 

original picture file as the file will be overwritten using this 

procedure. To do this:

1. Open Microsoft Office Picture Manager, select “Add a 

new picture shortcut.” After the window opens, select 

the folder containing the pictures you want to edit. The 

window will close and the photographs contained in the 

folder will be available. 

2. Hold the control key down and left click to select each 

image file(s) to be resized.

3. Right click and select “Edit Pictures.” After the sidebar 

appears, select “Resize.” 

4. In the “Resize Settings” sidebar, select the button for 

“Predefines with X height” and select “Document –

Small (800 x 600px). Click OK. 

5. New resized pictures will be created in Microsoft Office 

Picture Manager and are denoted by an asterisk in the 

picture name. The files must be saved for the change 

to take effect. Select “File” and select “Save.” The 

resized picture files will replace the files in the original 

source folder. If you want to keep the source picture 

files you must rename the resized files by selecting each 

file individually by selecting “File,” then “Save As,” and 

entering a new name. 

6. The resized photograph files are now ready for insertion 

into the eNSpect EIR document. Remember to maintain 

the original image files, not the resized digital image 

files, for filing with the hard copy exhibits and 

attachments in accordance with applicable procedures

To insert a picture into the eNSpect EIR document:

1. Open the eNSpect EIR document. Position cursor to 

where you want to insert the picture. 

2. From the menu bar, click on Insert, choose Picture, click 

on From File, find and select folder with resized pictures 

to be inserted. See Exhibit 5-7. 

3. Double click on the resized picture to be inserted. 

4. Picture inserted into the eNSpect EIR document can be 

made larger or smaller by clicking on the picture and 

grabbing the corner of the picture frame and dragging to 

achieve the desired size. 

5. Include the following information in the EIR narrative: 

the photo number; the date the photo was taken and by 

whom; and a brief narrative description of what the 

photo depicts.

Alternative method: Digital photographs can also be 

submitted as Exhibits to the EIR. A narrative description 

may be placed below the digital photograph. Include the 

photo number, the date photo was taken and by whom, and 

a brief description of what the photo depicts.

See also 5.3.8.2 - Identification of Records Collected. 

Photographs can be resized using Microsoft Office Picture 

Manager. See Exhibit 5-8 which shows the "resize" menu 

option.

NOTE: When any digital photos are used in an EIR, submit

the original or original copy of the camera images following 

procedures as outlined in IOM 5.3.4.3 – Preparing and 

Maintaining Digital Photographs as Regulatory Evidence.

5.3.4.5 - Photograph Requests

Do not routinely advise firms they may have copies of

photos. However, if management of the firm initiates the 

request, advise them it is possible to obtain copies of 

photographs taken in their plant under the Freedom of 

Information Act. Any request should be sent to The Food 

and Drug Administration, at the address listed on the FDA 

482 or FDA 483 or FDA 4056. The firm must bear the cost 

of duplicating the photographs. 

Since photographs are records in an investigative file, they 

are not available under the Freedom of Information Act until 

the file is closed.

Do not discourage firms from taking their own photographs 

at the same time and of the same scenes as you. 

5.3.5 - RECORDINGS

Under normal circumstances recording devices will not be 

used while conducting inspections and investigations. 

However, some firms are now recording and/or videotaping, the inspection and/or the discussion with 

management portion of the inspection. These firms should 

be advised we do not object to this procedure, but we will 

also record the discussion to assure the accuracy of our 

records. Occasionally a firm's management may record the 

serving of an inspection warrant or, in a hostile situation, 

may want to record everything. In such cases, depending 
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on the circumstances, you may prepare your own recording 

in parallel with the firm's recording. Do not depend on the 

firm to provide a duplicate of their recordings.

Use a clear tape cassette and identify the tape verbally as 

follows:

"This is Investigator ____________ of the U.S. Food and 

Drug Administration speaking in the (state location) of (firm 

name), (address), (city), (state), and (zip code). It is now 

a.m./p.m. on (date). Present are (list individuals present 

with title). This discussion is being recorded by both the 

representative of (firm name) and by me. We are going to 

discuss the inspectional findings of an inspection 

conducted at this firm on (inclusive dates)."

At the close of the discussion and prior to leaving the firm, 

the recording will be verbally identified as follows:

"This is Investigator ____________ speaking. It is now 

_______ a.m./p.m. on (date). This was a recording of the 

discussion with management at the conclusion of an 

inspection of (firm name and address) conducted on 

(dates).”

If the recording covers a different situation, the identification 

should be modified accordingly. If the representative of the 

firm refuses permission to record the discussion, continue 

with your discussion and report the facts in your EIR.

The tape cassette must be identified with the firm name, 

date of the inspection, and investigator's name. Program 

divisions have the option of transcribing the tape and 

making the transcription an exhibit for the EIR. However, 

the tape itself must be made a permanent part of the EIR 

as an exhibit.

5.3.6 - RESPONSIBLE INDIVIDUALS

The identification of those responsible for violations is a 

critical part of the inspection, and as important as 

determining and documenting the violations themselves. 

Responsibility must be determined to identify those persons 

to hold accountable for violations, and with whom the 

agency must deal to seek lasting corrections.

Document and fully report individual responsibility 

whenever;

1. It is required by the assignment,

2. Inspectional findings suggest the possibility of 

regulatory action, or

3. Background information suggests the possibility of 

regulatory action.

Under the Medical Device Quality System regulation (21 

CFR 820.20), if the management at the firm is not 

exercising the controls required by the regulation, the 

deviations may be cited on your FDA 483.

5.3.6.1 - Discussion on Duty, Power, 

Responsibility

Duty - An obligation required by one's position; a moral or 

legal obligation.

Power - Possession of the right or ability to wield force or 

influence to produce an effect.

Responsibility - An individual who has the duty and power 

to act is a responsible person.

Three key points to consider are:

1. Who had the duty and power to detect the violation?

2. Who had the duty and power to prevent the violation?

3. Who had the duty and power to correct the violation?

5.3.6.2 - Inspection Techniques How to 

Document Responsibility

Always determine and report the full legal name and title of 

persons interviewed, who supplied relevant facts and the 

name/title/address/email address of top management 

officials to whom FDA correspondence should be directed.

If an email address does not exist, this should be noted. 

Obtain the correct name and correct title of all corporate 

officers or company officials. Obtain pertinent educational 

and experience backgrounds, and the duties and powers of 

the officers and employees in key managerial, production, 

control, and sanitation positions. Ascertain the experience 

and training of supervisory personnel, in terms that will 

describe their qualifications to carry out their 

responsibilities.

There are numerous ways to establish and document 

responsibility. Evidence may be obtained during interviews 

and record review specifically intended to determine 

responsibility. Cover and report items such as:

1. Organizational charts, 

2. Statements by individuals admitting their responsibility 

or attributing responsibility to others,

3. Company publications, letters, memos and instructions 

to employees, and

4. The presence or absence of individuals in specific areas 

at specific, significant times, and their observed 

activities directing, approving, etc.

In order to establish relationships between violative 

conditions and responsible individuals, the following types 

of information, would be useful:

1. Who knew of conditions?

2. Who should have known of the conditions because of 

their specific or overall duties and positions?

3. Who had the duty and power to prevent or detect the 

conditions, or to see they were prevented or detected?

4. Who had the duty and power to correct the conditions, 

or to see they were corrected? What was done after 

person(s) learned of the conditions? Upon whose 

authority and instructions (be specific)?
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5. What orders were issued (When, by whom, to whom, on

whose authority and instructions)?

6. What follow-up was done to see if orders were carried 

out (when; by whom; on whose authority and 

instructions)?

7. Who decided corrections were or were not complete and 

satisfactory?

8. What funding, new equipment, new procedures were 

requested, authorized or denied in relation to the 

conditions; who made the requests, authorizations, or 

denials.

Duties and power related to general operations should be 

established to supplement the specific relationships to 

violations. Examples of operational decisions that indicate 

responsibility are:

1. What processing equipment to buy.

2. What raw materials to purchase.

3. What products to produce and what procedures to follow 

in production?

4. Production schedules - how much to produce, what to 

make, when to stop or alter production?

5. What production controls to be used?

6. What standards are set for products, raw materials, 

processes?

7. How to correct or prevent adverse conditions; how much 

to spend and whom to hire to correct or prevent adverse 

conditions; when to clean up?

8. How products will be labeled; what products to ship; 

label approval?

9. When to reject raw materials or products; when to 

initiate a recall; acceptable quality levels for products?

10.When to hire or fire personnel?

11.Who will accept FDA 482, Notice of Inspection; refuses 

inspection; accept Inspectional Observations, FDA 

483?

12.Who designed and implemented the quality assurance 

plan; who receives reports of Q.A.; who acts or should 

act upon the reports?

13.Who is responsible for auditing other facilities, 

contractors, vendors, GLP sites, etc.?

14.In the firm's business relationships, who signs major 

contracts, purchase orders, etc.? 

In some circumstances, documenting of individual 

responsibility requires investigative techniques that lead to 

sources outside the firm. These sources may include 

contractors, consultants, pest control or sanitation services, 

local health officials and others. Copies of documents 

between the firm and outside parties may help establish 

responsibilities. Do not overlook state officials as another 

possible source of information in selected cases.

During the course of the inspection you may observe 

persons who hold responsible positions and/or influence in 

the firm whose abilities or judgment may be affected by an 

obvious infirmity, handicap, or disability. If it is obvious the 

infirmity adversely affects the person's responsibilities or 

duties that are under FDA oversight, describe in your EIR 

the extent of the infirmity and how it relates to the purported 

problem or adverse condition.

5.3.7 - GUARANTEES AND LABELING 

AGREEMENTS

Review the Code of Federal Regulations, 21 CFR 7.12, 

7.13, 101.100(d), 201.150, and 701.9, for information 

concerning guarantees and labeling agreements.

5.3.7.1 - Guarantee

Certain exemptions from the criminal provisions of the 

FD&C Act are provided where a valid guarantee exists as 

specified in Section 303(c) of the FD&C Act [21 U.S.C. 333 

(c)]. Obtain a copy of any Food and Drug guarantee, which 

the firm claims to use relating to a violation noted during 

your inspection. No person may rely upon any guaranty 

unless he has acted merely as a conduit through which the 

merchandise reached the consumer.

5.3.7.2 - Labeling Agreement

Products regulated by FDA are normally expected to be 

completely labeled when introduced into or while in 

interstate commerce. Under certain conditions exemptions 

are allowed when such articles are, in accordance with 

trade practices, to be processed, labeled, or repacked in 

substantial quantity at an establishment other than where 

originally processed or packed. Sections 405, 503(a) and 

603 of the FD&C Act [21 U.S.C. 345, 353(a), and 363] also 

provide exemptions from complete labeling for products.

5.3.7.3 - Exemption Requirements

To qualify for this exemption, the shipment must meet one 

of the following:

1. The shipper must operate the establishment where the 

article is to be processed, labeled or repacked; or

2. If the shipper is not the operator of the establishment, 

he must first obtain from the owner a written agreement 

signed by and containing the post office addresses of 

such persons and such operator and containing such 

specifications for the processing, labeling or repacking 

of such articles as will insure that such article will not 

be adulterated or misbranded within the meaning of the 

Act, upon completion of the processing, labeling or 

repacking.

Submit copies and dates of written agreements where 

unlabeled articles are shipped in interstate commerce.

5.3.8 - RECORDS OBTAINED

Many types of inspections and investigations require 

collection of copies of records to document evidence of 

deviations. In some cases, this may involve voluminous 

copies of Good Manufacturing Practice (GMP) records, 

commitments made in the Pre-Approval process, 

adherence to the requirements of the Low Acid Canned 

Food regulations or other areas. Copies of records are also 

obtained to document interstate commerce, product 

labeling and promotion, and to identify the party or parties 

responsible for a variety of actions. Copies of records can 
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be obtained in paper format or electronic format. All 

records become part of the government's case should it go 

to litigation.

Normally, during litigation proceedings, the best evidence 

rule prevails in court, whereby the copy of the record in the 

custody of the government can be authenticated, if the 

original record is not produced by the custodian of the 

record.

It is imperative the government witness [usually the 

collector of the record(s)] be able to testify where, when and 

from whom the copies were obtained, and that the copy is 

a true copy of the source record, based on their review of 

the source record.

5.3.8.1 - Verification of Source Records

You must verify the copy of the record(s) you received is an 

accurate representation of the original or source record(s) 

so you are able to testify your copy is an exact duplicate of 

the original or source record. Record in your regulatory 

notes you authenticated copies of records and when, 

where, and from whom copies were obtained.

Do not write on, highlight, or otherwise alter copies of 

original records obtained from the firm as they will no longer 

be an accurate representation of the source record. The

Investigator may write on a second copy of records, 

provided they include both a copy of the original or source 

record and their altered copy as exhibits to the EIR.

5.3.8.2 - Identification of Records Collected

Articles used as evidence in court cases must be identified 

so you can later testify the records entered as evidence are 

the very ones you obtained. This includes all records as 

noted in IOM 5.3.8, and any others for evidence in 

administrative or judiciary proceedings. When identifying 

and filing records, you must ensure the record is complete 

and no identification method or filing mechanism covers, 

defaces or obliterates any data on the record.

You must identify records submitted in support of an 

inspection or investigation, including records provided in an 

Establishment Inspection Report (EIR) or narrative 

memorandum. The identification must positively identify the 

specific copies you received during your inspection or 

investigation and to avoid any filing mix-up. If labels are 

used to identify records, they must be permanently applied 

so any removal will be obvious.

Electronic labeling should be used to identify records 

collected. Identification should include at least the firm 

name, FEI Number, date(s) of the inspection, the initials of 

all FDA participants, exhibit number and page number(s). 

Refer to ORA-OO.004, “Using eNSpect to Create, Store, 

and Preserve Electronic Records Associated with an 

Establishment Inspection Report,” When you collect a 

sample, each page of the copied records will become part 

of the collection report and should be identified as noted in 

IOM 4.4.2. Examples include records of interstate 

commerce, manufacturing deviations, label and labeling 

violations. Records submitted with a memorandum of 

investigation will be identified with the firm or subject name, 

the date(s) of the investigation, the initials of all FDA 

participants, and page number. 

There are occasions when a single record may include 

hundreds of sheets of bound paper. Abbreviated methods 

of identification may be used for bound records by fully 

identifying the first and last few pages. In some cases, firm's 

clearly mark each page with the sequential and total pages 

number (e.g., page 6 of 10, 7 of 10, etc.) and this allows 

you to fully mark only a few pages in the beginning and end 

of the exhibit.

All pages must be identifiable if not in bound records. One 

example of a shortened method of identifying individual 

exhibits containing a large number of pages (usually more 

than 25) is to fully identify the first few and last few pages 

with at least the exhibit number, date and the initials of all 

FDA participants. Then identify the remaining pages with 

the page number of the total page numbers, and your 

initials, e.g., "5 of 95 SHR". This may not be acceptable if 

you have more than one exhibit consisting of exactly 95 

pages.

Whatever method is used, you must assure the record is 

complete and is always identifiable. This is so you can 

testify as to the "where", "when" and "from whom" the 

copies were obtained, and that the copy is a true copy of 

the source record based on your review of the source 

record. The identification method should allow any reviewer 

to determine if the record is complete or pages or parts are 

missing.

5.3.8.3 – Electronic Records, Microfilm and 

Microfiche

When attempting to obtain records, you may find they are 

stored on microfilm, microfiche, or some form of a 

computerized management information system as 

electronic records. Records obtained during the course of 

the inspection in these forms are handled the same as any 

records following procedures outlined in IOM 5.3.8.1 and 

5.3.8.2.

5.3.8.3.1 - ELECTRONIC RECORDS

Electronic records are defined in 21 CFR 11.3(b)(6) as 

any combination of text, graphics, data, audio, pictorial, or 

other information representation in digital form that is 

created, modified, maintained, archived, retrieved, or 

distributed by an electronic system. This term applies 

specifically to records in electronic form that are created, 

modified, maintained, archived, retrieved, or transmitted, 

under any records requirements set forth in agency 

regulations. This also applies to electronic records 

submitted to the agency under requirements of the 
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Federal Food, Drug, and Cosmetic Act and the Public 

Health Service Act, even if such records are not 

specifically identified in agency regulations. In both 

instances, these records will be maintained and handled 

as identified in 5.3.8.3.3.

Electronic data obtained from a firm provides an 

investigator with a wealth of information which can be 

used to assess their compliance with the FD&C act and 

promulgated regulations. If there are no mechanisms 

available for a firm to securely transmit the data 

electronically to the investigator, the data may be provided 

to FDA via electronic storage media. Secure means of 

transmittal may include approved cloud file sharing or use 

of FDA Electronic Submissions Gateway. Refer to your 

program for approved methods of secure transmittal, as 

well as instructions that can be provided to regulated 

industry. 

Data received on movable media presents a challenge 

with IT security as well as physical security of the media. 

The information obtained from the firm is commercial 

confidential information (CCI) and as such must be 

protected to the greatest extent possible. It is the 

responsibility of the investigator to make sure the physical 

data source remains secure. Likewise, data obtained from 

extra‐governmental sources may contain viruses or 

malware that may be included with the information 

provided to the investigator either on purpose or 

accidentally. The transfer of electronic data must be 

evaluated along with concerns related to safeguarding the 

security of both FDA and firm information. ORA 

investigators must be very cognizant of issues that may 

arise with the use of electronic media and be vigilant while 

using it.

If secure methods of transmission are not available, 

electronic data can be obtained by receiving electronic 

media from the firm or by providing a clean, preformatted 

electronic media to the firm. ORA procedures for the use 

of electronic media will be identical for both domestic and 

foreign inspections/investigations. Those foreign locations 

which may present a security challenge will be handled on 

a case‐by‐case basis through the foreign trip planning 

process and will be discussed with the investigator prior to 

departing the United States.

The Device Control Data Loss Prevention (DLP) tool at 

FDA blocks most FDA users from using unauthorized 

USBs, as this is against FDA security policy as described 

in FDA Staff Manual Guide 3251.12, Appendix Z. Certain 

ORA Investigators have an exception and are permitted 

read access to firm‐provided USBs in order to transfer 

data onto their machines. However, they are not permitted 

write access, as FDA data should not be written to a 

device that is not FIPS 140‐2 compliant and/or approved 

on the FDA Master Approved Technologies (MAT) list. If 

you are an investigator and are having problems 

accessing content on a firm‐provided USB, please contact 

your ISSO.

5.3.8.3.1.1 ORIGINAL COPY

An original copy is an unaltered copy of a source electronic 

record. Original copies collected to support observations of 

potential violations or used as evidence in administrative or 

judiciary proceedings, including any original copy included 

in an EIR, memorandum, or C/R, must be stored as to 

maintain the chain of custody and assure the records may 

be verified any time after collection.

5.3.8.3.1.2 WORKING COPY

A copy of an electronic record which is created from the 

original copy and is used to review and analyze the records, 

so as to not alter the original copy. This is an exact copy of 

the original copy electronic records.

5.3.8.3.2 - ELECTRONIC DATABASES AND 

QUERIES

Firms may use proprietary programs developed in‐house 

or off the shelf programs to generate and/or store records 

used to show regulatory compliance, such as blood bank 

databases, drug production records, medical device 

complaints, and/or service records. These programs can 

often times be queried to generate electronic databases or 

summary data in a commonly used file format, such as 

Microsoft Excel. During an establishment inspection you 

may request and receive electronic databases or 

summary data generated by the firm from their databases. 

The methods used must maintain the integrity of the 

electronic data and prevent unauthorized changes. 

Do not personally access a firm’s system to review 

electronic records, databases, or source data during the 

course of an inspection, unless:

• it is a bioresearch monitoring inspection which 

meets the criteria outlined in section 5.10.2.1 or 

• a biologics inspection where it is not practical to 

oversee the firm’s personnel while they access 

their system, follow section 5.7.2.5.1 . 

Secure methods of transmitting this data to the FDA for all 

other types of inspections may be used to obtain these 

files for review. 

When it is necessary to access a firm's data during an 

inspection:

1. Oversee the firm's personnel accessing their 

system and have them answer your questions.

2. Request the firm run queries specific to the 

information of interest.

3. Request the firm provide the parameters used to 

generate the data.

4. Request the firm to transmit the electronic data 

securely to FDA, or provide it on electronic storage media.

Firm electronic data can be dynamic with real time 

updating. Your request may require the firm to develop 

one or more custom queries to provide the requested 

information. A custom report query is the method of using 

the reporting software to pull the specific data requested 
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during the inspection (i.e., all complaints from the last 12 

months with specific data fields). You must assume the 

query logic is not validated and take appropriate action to 

ensure the data is accurate and no data has been 

accidentally omitted due to a programming logic error 

occurring at the firm.

Reviewing electronic data may require its transfer to 

electronic storage media for you to use in your computer if 

a method of secure transmittal is not available; see 

section 5.3.8.3.3.1 below for information on how to handle 

electronic storage media. Do not use the firm's equipment 

or personnel to perform computerized data manipulation 

for the purposes of review and analysis.

5.3.8.3.2.1 - REQUESTING Electronic 

RECORDS from databases

Before requesting a copy of computerized data, you should 

determine several things including information about the 

size and contents of the database, the program used by the 

firm, and the program you will use, among others. The 

following steps are useful in preparing for an electronic 

database request.

1. Determine the firm's application program used to 

maintain the data of interest. It is best to obtain data files 

in a format compatible with application programs

currently used by the agency. Check the program you 

plan to use to ensure it can handle the file size you will 

be using.

2. You should determine what fields of information are 

routinely captured by the firm. This can be accomplished 

by requesting a printout of the data structure of the data 

file or observing the inputting of data at a computer 

terminal or workstation. It is common for databases to 

contain numbers or other coded information requiring 

translations from look up tables to give meaningful text. 

You should determine if information fields contain coded 

data, and if so, a code breakdown should be obtained. 

Information about code breakdowns should be located 

in the SOPs for that computerized system. Also, be 

aware in relational databases, there may be linking data 

fields that exist in other tables that should also be 

considered in the overall data request.

3. If the files are too large to be securely transmitted or fit 

on electronic storage media, file compression can be 

used. If possible, ask that the firm prepare the data in a 

compression format that is self-extracting. Selfextracting files are executable files and should be virus 

scanned before and after executing. All electronic 

storage media should be scanned prior to being used on 

any FDA computer. Whatever compression utility is 

used, make sure you have the software to manipulate 

the files as needed.

5.3.8.3.2.2 - ELECTRONIC RECORDS 

RECEIVED VIA SECURE TRANSMISSION OR 

ON ELECTRONIC STORAGE MEDIA

If you provide the electronic storage media to the firm, use 

only clean and preformatted media. An additional 

safeguard is to request the firm reformat the media on their 

own computer to assure it is usable and “clean”.

Any request for electronic records on electronic storage 

media should be made with a computer application in mind 

and the information obtained should be useful. The 

electronic records should be in a format compatible with 

software applications knowledgeable to you and available 

from the Agency. Certain types of file conversion are 

difficult and should not be attempted without the necessary 

knowledge and availability of conversion type programs 

where applicable. Other file conversions are simple and 

have standard, built in conversion programs, such as 

converting a Microsoft Word document to an Adobe PDF. If 

help is needed for file conversion, assistance may be 

available within the program division.

When records are received via a secure transmission 

method, the resulting file made available to the CSO must 

be treated as the original copy. A working copy of the file 

should be created, and the original transferred to a secure 

directory for preservation in accordance with program 

records management procedures, as it may be used to 

support observations of potential violations, or used as 

evidence in administrative or judicial procedures. 

Any electronic storage media containing electronic records 

received during the course of an inspection should be 

considered and handled as the original copy. The original 

copy (USB, CD, DVD, etc.) of electronic records should be 

secured to assure the integrity of the data when used to 

support observations of potential violations or used as 

evidence in administrative or judicial proceedings. Seal with 

an FDA-415a in an FDA-525 or similar envelope. Complete 

blocks 2, 3, 5, 7, and 12 of the FDA-525 and seal with an 

Official Seal, FDA-415a. If you use a larger envelope, 

identify the envelope with your name, title, Home District 

and Program Division, date, firm name, firm address 

(include zip code), and description of the contents of the 

envelope. Mark the FDA-525 or similar envelope as 

containing electronic storage media or other media and 

document the software type and version(s) required to open 

the included software, e.g. Microsoft Word 2016, Microsoft 

Excel 2016, or Windows Photo Viewer. The electronic 

storage media or other media should be stored as part of 

the hardcopy exhibits in the designated file room. See IOM 

5.11.5.1.

There are no guarantees the files provided via secure 

transmission on electronic storage media will be usable 

data. It is your responsibility to make a working prior to 

closing the inspection. You will need to view the copied 

files and verify the files contain the information requested 

and the information is useable to you. 
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If you perform analysis of the data, including sorts, pivot 

tables, or other reviews, on the working copy of an 

electronic database to develop or support observations, 

you should request the firm conduct the same analysis and 

provide a copy of this analysis (the firm is under no 

obligation to do so.) This can be done by requesting an 

electronic database that includes only the information of 

interest (e.g. an Excel spreadsheet of failures of a certain 

type for a specific time period), or requesting a paper copy 

of the information of interest.

5.3.8.3.3.1 - IDENTIFYING AND SECURING 

ELECTRONIC STORAGE MEDIA

When electronic storage media is used to obtain electronic 

records you should follow these steps to ensure its proper 

identification and security:

1. Label each original copy of electronic storage media

a. Firm name

b. Date and your initials

c. If you provide the disk(s)/USB to be used, use only 

new and preformatted disk(s)/USB.

d. The name of the appropriate software and version 

to ensure readability of the information.

2. Make a working copy of the electronic storage media

a. Virus scan the original storage media

i. Disconnect your machine from the FDA network, 

the VPN, and the internet.

ii. Insert the Media into your computer (USB into 

USB port or CD/DVD into drive).

iii. Do NOT click ok on or accept any Windows 

prompts for driver installations.

iv. Right Click on the drive of interest.

v. Select "Scan for threats..."

vi. When the window identified in Figure XX 

appears, select “Continue.”

(1) We do not want to “Clean” the data as it 

may be used as evidence if a virus or 

malware was detected.

vii. If the scan is clean, proceed forward. If the scan 

detects a problem, the security scanning tool 

should quarantine the file(s). At this point, the 

file(s) will not be accessible, and you should put 

in an ERIC ticket to report the incident (which 

should be assigned to the FDA Incident 

Response team). If the scan reveals malware or 

a virus, maintain chain of custody on the 

electronic media. Alert the SCSO of the issue 

and the steps taken.

b. Check the security on the storage media by viewing 

the “Security” tab under the “Properties” window 

(right click). This will ensure you have the ability to 

view and analyze the data.

c. Copy the original information from the electronic 

storage media onto a working copy.

d. Verify the data is useable.

3. Identify and place the original copy of electronic storage 

media as identified in 5.11.5.1.

4. Prepare electronic record(s) for inclusion in the EIR, 

Memorandum, or C/R.

5.3.8.5 - Listing of Records

If management requests a list of the copies of records you 

obtain, prepare it in duplicate and leave the original with the 

firm. Many firms prepare duplicate copies of documents 

requested during our inspections. In the interests of 

conserving inspectional time, you may ask the firm to 

prepare the list of copies concurrently with the 

photocopying and you then verify the accuracy. Do not use 

form FDA-484, Receipt for Samples. Describe the 

circumstances in your report including the name and title of 

the individual to whom you gave the list. Submit the 

duplicate list with your report as an exhibit.

5.3.8.6 - Patient and/or Consumer 

Identification on Records

During the course of many types of inspections and 

investigations you will review and collect records which 

specifically identify (by name) patients or consumers. 

Under most state Privacy Laws this information is 

confidential. Some firms we inspect may mistakenly believe 

this information is not releasable to the federal government. 

However, Federal laws preempt State laws; with few 

exceptions we are entitled to review and copy the complete 

record, including the identifying patient/ consumer names. 

The Agency is then required to maintain the confidentiality 

of the records/files, as with any confidential record you 

collect. See IOM 5.10.5. Any disclosure of the information 

contained in the record(s) can only be by Law, i.e., judge's 

order, disclosure, Congressional order, etc. If you 

encounter resistance from the firm in providing patient 

records, you may refer them to 45 CFR 164.512(b) which 

explains the exemptions allowing FDA access to the patient 

records.

General, routine guidance is as follows:

1. For records copied as a result of injury or complaint 

investigation, where you obtain patient identification, the 

identification should remain intact and stored in the 

official FDA files. Frequently, medical releases must be 

obtained from a complainant, consumer or "next-of-kin". 

At least one or two extra should be obtained and stored 

in the files.

2. For any inspection/investigation involving a regulation 

required Informed Consent, such as clinical 

investigations, IRBs, bioequivalence testing, etc., 

patient identification should remain intact and stored in 

the official FDA files.

3. For most others, such as MQSA, plasmapheresis, blood 

donations, etc., only the patient initials and unique 

identifier supplied by the firm (such as donor number, 

donation number, etc.) need be routinely retained in the 

FDA files.

It is not uncommon for a firm to voluntarily purge the 

documents of the pertinent identifiers as they are copied. 

You must verify (by direct comparison to the original 
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document) you received an accurate reproduction of the 

original, minus the agreed to purging, prior to accepting the 

copy.

As with any inspection there are times when the specific 

identifiers must be obtained, copied and retained, such as 

if/when further interview of the patient/consumer could be 

necessary. If in doubt, obtain the data. It is always easier to 

delete later than to return to obtain the information, 

especially in the few cases where questionable practices 

may result in the loss of the information.

All documents obtained containing confidential identifiers 

will be maintained as all documents obtained by FDA 

containing confidential information, i.e., in the official FDA 

files. Confidential identifiers may be flagged in the official 

FDA files for reference by reviewers to assure no 

confidential data are released under FOIA.

5.3.9 - REQUEST FOR SAMPLE COLLECTION

There are times one program division will request another 

program division to collect surveillance or compliance 

samples for it. The requesting program division should 

provide as much of the following information as is available 

on specific shipments, using the FACTS Create Sample

Assignment Screen. See IOM Exhibit 5-9. 

The following fields must be completed in order to save the 

assignment: Requesting Organization, Priority, Subject, 

POC Name, Op Code, Accomp Org, Num of Ops, and PAC. 

When you create a sample collection assignment, which 

will require laboratory analysis, you should also create an 

assignment for the laboratory, using operation 41.

The screen is organized in sections.

5.3.10 - POST-INSPECTION NOTIFICATION 

LETTERS

Issuance of Post-inspection notification letters have been 

discontinued in all program areas. See FMD 145. 

SUBCHAPTER 5.4 – FOOD AND COSMETICS 

INSPECTIONS

5.4.1 - FOOD and COSMETIC INSPECTIONS

Food inspections are conducted to evaluate the methods, 

facilities, and controls used in manufacturing, storage and 

distribution of foods.

Cosmetic Inspections are conducted to determine wether 

cosmetics are being manufacturered in a manner that 

ensures products adequately meet all statutory and 

regulatory requirements so as to be safe for consumers to 

use.

See CFSAN Office of Compliance's intranet website for the 

most current guidance (e.g., compliance programs, field 

assignments, field guidance).

5.4.1.1 - Preparation and References

Before undertaking an inspection of food see items 1-11 

below. For inspection of cosmentics see items 1,2,3,5,6,7, 

and 8 below: 

1. Review the program division files of the firm to be 

inspected and acquaint yourself with the firm's history, 

related firms, trademarks, practices and products. The 

review will identify products difficult to manufacture, 

require special handling, special processes or 

techniques, and hours of operation, which is especially 

important in bacteriological inspections. Remove, for 

subsequent investigations and discussion with 

management, Complaint/Injury Reports, which are 

marked for follow-up during the next inspection. See 

IOM 5.2.8.

2. Become familiar with current programs relating to the 

particular industry involved and relevant DDHAFO

Inspection Guides. Become familiar with any applicable 

Compliance Policy Guide . 

3. Understand the nature of the assignment and whether it 

entails certain problems, e.g., Salmonella or other 

bacteriological aspects.

4. Review the FD&C Act Chapter IV - Food.

5. Review and become familiar with the appropriate parts 

of 21 CFR pertaining to foods and cosmetics. All CFRs 

can be found here. 

Food 21 CFR 101-190

Cosmetics 21 CFR 700-740

Control of 

Communicable 

Disease

21 CFR 1240

Interstate 

Conveyance

21 CFR 1250

6. Determine the type operation to be inspected to ensure 

application of the appropriate regulations. 

7. Ensure that you have received all necessary training

that may be required. Consult your supervisor with 

questions.

8. Review implementation dates of regulations to ensure 

application of the appropriate regulations. 

9. Review reference materials on food technology and 

other subjects. 

10.If you are assigned to inspect food-service 

establishments under the FDA - Secret Service 

Agreement, you should use the most current copy of the 

"Food Code" and be standardized in its use. All Food 

Service Specialists and most Interstate Travel 

Sanitation Specialists are standardized in use of the 

code.

11.Be familiar with the "Food Chemicals Codex". See IOM 

5.4.4.3.
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5.4.1.2 - Inspectional Authority

See IOM subchapter 2.2 for broader information on this 

topic.

Authority to Obtain Records and Information in LACF and 

Acidified Foods Plants:

FDA's regulation in 21 CFR 113 requires commercial 

processors of low-acid foods packaged in hermetically 

sealed containers to maintain complete records of 

processing, production and initial distribution. 21 CFR 114

requires the same of commercial processors of acidified 

foods. 21 CFR 108.25(g) and 21 CFR 108.35(h) provide 

that a commercial processor shall permit the inspection and 

copying of the records required by 21 CFR 113 and 21 CFR 

114 by duly authorized employees of FDA. The demand for 

these records must be in writing on an FDA 482a, Demand 

for Records, signed by you and must identify the records 

demanded.

5.4.1.2.1 - WRITTEN DEMAND FOR 

RECORDS

To obtain the records:

1. Prepare an FDA 482a, "Demand for Records", listing the 

records demanded. Describe the processing records to 

be reviewed and/or copied as accurately as you can, 

e.g., “All thermal process, production, and quality control 

records, including analytical records and maintenance 

records which may document any changes to the 

equipment or the thermal process that are mandated by 

21 CFR 108, 113 and 114 for all Low Acid Canned Food 

(LACF) or Acidified Food (AF) produced at this facility.” 

If only a specific record is desired list it specifically as 

follows: e.g., "Fill Weight Records for #2 Filling Machine 

for the period of 4-15-17 through 6-7-17." 

2. Sign the form.

3. Issue the original to the same person to whom the FDA 

482, "Notice of Inspection", was issued.

4. Submit an exact copy with your EIR.

5.4.1.2.2 - WRITTEN REQUEST FOR 

INFORMATION

21 CFR 108.35(c)(3)(ii) states commercial processors 

engaged in thermal processing of low-acid foods packaged 

in hermetically sealed containers shall provide FDA with 

any information concerning processes and procedures 

necessary by FDA to determine the adequacy of the 

process. 21 CFR 108.25(c)(3)(ii) requires the same of 

commercial processors of acidified foods. The information 

in this regulation is the data on which the processes are 

based. Many processors will not have this information and 

in fact 21 CFR 113.83 requires only that the person or 

organization establishing the process permanently retain all 

records covering all aspects of establishing the process. 

The processor should, however, have in his files a letter or 

other written documentation from a processing authority 

delineating the recommended scheduled process and 

associated critical factors.

You may encounter situations where you believe control of 

certain factors is critical to the process and there is no 

evidence to document these factors were considered when 

the process was established (e.g., a change in formulation 

which could affect consistency). It is appropriate to issue a 

written request for a letter or other written documentation 

from a processing authority, which delineates the 

recommended scheduled process and associated critical 

factors. This represents the processing authority's 

conclusions and should correlate with the filed process.

If you believe control of certain factors are critical to the 

process and are not delineated in the process authority's 

recommendation or the filed process, obtain all available 

information about the situation. Include the name of the 

person or organization who established the process and the 

specific practices of the firm. This information should be 

included in your report and forwarded by your program 

division to the Center for Food Safety and Applied Nutrition, 

Division of Enforcement (HFS-605) for review, as soon as 

possible. If the process establishment data and information 

is deemed necessary by the center, they will either request 

it directly from the processor or will direct the program 

division to request it. If requested to obtain the information:

1. Prepare an FDA 482(b) - Request for Information listing 

the specific information requested. Specify each product 

involved by food product name and form, container size 

and processing method. For example, “All documents 

and records mandated by 21 CFR 108, 21 CFR 114.83 

and 21 CFR 113.83 relating to or having a bearing on 

the adequacy of processes for all Low Acid Canned 

Food (LACF) or Acidified Food (AF) products that are 

manufactured, processed or packed by this firm. 

2. Sign the form.

3. Issue the original to the same person to whom the FDA 

482, "Notice of Inspection", was issued.

4. Submit the carbon copy or exact copy with your EIR.

5.4.1.3 - Records Access Under Sections 414 

and 704 of the FD&C Act

The Food Safety Modernization Act amended Section 414 

of the Act to provide FDA with access and the ability to copy 

records under the following circumstances:

1. FDA has a reasonable belief that an article of food, and 

any other article of food that FDA reasonably believes is 

likely to be affected in a similar manner: 

a. Is adulterated and presents a threat of serious 

adverse health consequences or death to humans or 

animals, and 

b. The records are needed to assist FDA in determining 

whether the food is adulterated and presents a threat 

of serious adverse health consequences or death to 

humans or animals.

2. FDA believes that there is a reasonable probability that 

use of or exposure to an article of food, and any other 
CHAPTER 5 INVESTIGATIONS OPERATIONS MANUAL 2023 

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article of food that the FDA reasonably believes is likely 

to be affected in a similar manner: 

a. Will cause serious adverse health consequences or 

death to humans or animals, and 

b. The records are needed to assist FDA in determining 

whether there is a reasonable probability that the use 

of exposure to the food will cause serious adverse 

health consequences or death to human or animals.

If, during an inspection, you believe the above conditions 

exist, and: 

1. The firm refuses to provide access to the records, or

2. Based on past experience, the program division

anticipates that the firm may refuse to provide access to 

records, or 

3. The firm requests FDA to provide a separate written 

request for records,

Notify your supervisor and consult with your program 

division Compliance Branch.

Program division management will obtain DE concurrence 

before you issue the Form FDA 482c Notice of Inspection - 

Request for Records See Exhibit 5-10. Program division

management will notify FDA's Office of Emergency 

Operations (OEO) of any situation requiring issuance of 

Form FDA 482c. (OEO contact number: 1-866-300-4374 or 

301-796-8240 - 24 hours/day.) OEO will notify CFSAN or 

CVM, as appropriate, OHAFO, DE and OCC according to 

standard operating procedures to obtain a determination 

that the situation warrants issuance of Form FDA 482c. 

DE, in consultation with CFSAN or CVM OEO, OHAFO and 

the Program division, will determine if the standards for 

records inspection in paragraphs (1) or (2) of section 414(a) 

have been met and identify the scope of the records to 

request. Issue an FDA 482c, Notice of Inspection – 

Request for Records. See Exhibit 5-10 according to their 

instructions. 

FDA may at a later time, request additional records related 

to the same article of food, or other article of food that is 

likely to be affected in a similar manner, as long as the 

criteria in 414(a)(1) or (a)(2) continue to be met. The 

request for additional records may be verbal or written as 

necessary to facilitate access to the records.

Investigators should document in the EIR a firm’s refusal to 

allow access to records or a firm’s request for a written 

request for records and issuance of Form FDA 482c. 

5.4.1.4 - Food and Cosmetic Defense 

Inspectional Activities

Food and cosmetics security inspectional activities should 

be conducted during all routine food and cosmetics safety 

inspections. During the normal course of the inspection be 

alert to opportunities for improvement or enhancement of 

the firm’s food and cosmetics security preventive 

measures, as compared to those recommended in the 

guidance documents described below. You should not 

perform a comprehensive food and cosmetics security audit 

of the firm or conduct an extensive interview of 

management or employees in an attempt to determine the 

level of adoption of preventive measures listed in the

guidance. The goal is to facilitate an exchange of 

information to heighten awareness on the subject of food 

and cosmetics security.

5.4.1.4.1 - FOOD AND COSMETIC SECURITY

Inspectional activities relative to food and cosmetic security 

for routine food and cosmetic establishment inspections 

should include:

1. Discussion with firm management of relevant FDA 

guidance documents including:

a. FDA Firm Resources

b. Draft Guidance for Industry: Mitigation Strategies to 

Protect Food Against Intentional Adulteration. 

c. Retail Food Stores and Food Service 

Establishments: FSMA Final Rule for Mitigation 

Strategies to Protect Food Against Intentional 

Adulteration

These documents should be used as references during 

inspections, as appropriate. If firm management does 

not already have a copy of the relevant guidance 

documents provide them with hard copies or 

information on how to obtain the guidance from FDA’s 

web site. 

2. Identification of opportunities for improvement or 

enhancement of the firm’s food and cosmetic security 

preventive measures, as compared to those 

recommended in the guidance documents, and 

encouragement of management to make such 

improvements or enhancements to their security 

system.

Keep in mind that guidance does not represent mandatory 

conditions or practices; some of the recommended food 

and cosmetics security preventive measures may not be 

appropriate or practical to the specific operation; and other 

means of achieving the goals of the preventive measures 

listed in the guidance may be more suitable for the specific 

operation than those cited as examples. The important 

message for management is to consider the goals of the 

food and cosmetics security preventive measures; evaluate 

the goals relative to the specifics of their operation; and 

address those that are relevant to the extent practical.

Food and cosmetics security observations should not be 

listed on form FDA-483, Inspectional Observations, unless 

they likewise constitute deviations from Current Good 

Manufacturing Practice. Security discussions should be 

handled discretely and should only involve management of 

the firm.

The fact that the discussion took place and, if applicable, 

that a copy of the guidance document(s) was provided 

should be recorded in the summary section of the EIR. For 

example, under a section heading titled “Food and 

Cosmetics Security” you should only state, “A copy of the 

FSMA Final Rule for Mitigation Strategies to Protect Food 

Against Intentional Adulteration documents were provided 
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to and food and cosmetics security issues were discussed 

with (name of firm official).” The details of inspectional 

findings regarding security should NOT be recorded. You 

should also minimize the quantity and detail of notes taken 

relative to the firm’s food and cosmetics security program, 

recording only items needed to serve as a “memory jog” 

during the discussion with management.

5.4.1.4.2 - RECONCILIATION EXAMINATIONS

During routine food and cosmetic inspections, conduct one 

reconciliation examination during each food and cosmetic 

establishment inspection. The examinations are to be 

conducted on raw materials used in the manufacture of 

foods or cosmetics, or finished products received by the 

firm for further distribution. Preference should be given to 

products of foreign origin. Where possible, these 

examinations should be performed on products as they are 

received by the firm.

Consult the factory jacket for any information on special 

conditions in the facility that may affect selection of 

personal protective equipment; consult your supervisor for 

any recommendations on personal protective equipment; 

and have available all necessary personal protective 

equipment to conduct the activity.

As Part of an Import Field Examination and Entry Review -

See IOM 6.3.1 and 6.4.3. For imported food and cosmetics, 

a reconciliation examination should be conducted:

1. Per Part A [IOM 5.4.1.4.3] during all routine import field 

exams. You should only report time under the Counter 

Terrorism PAC at the direction of your supervisor or if 

there is a for cause assignment.

2. In instances where review of entry information raises 

suspicion (resulting in a detailed reconciliation exam per 

Part B [IOM 5.4.1.4.4]).

A detailed reconciliation exam should be conducted when 

there are anomalies in entry declaration information. These 

may include new, unusual, or unfamiliar commodities, 

manufacturers, importers; suspicious trans-shipments; or 

credibility issues such as those between the product and 

declared country of origin.

If anomalies are found, entry documents should be 

requested and reviewed for discrepancies between the 

information declared through electronic filer submissions 

and that found in entry documents. Entry documents may 

include invoices, bills of lading, export certifications, and 

other relevant documents obtained from the importer, filer, 

or manufacturer/processor of the product. Fields in which 

discrepancies are found that may raise concern include 

country of origin, manufacturer, product description, 

product code, and quantity.

Avoid duplication of examination of the same foreign 

manufacturer, unless a prior reconciliation examination 

disclosed an unexplained discrepancy.

Follow guidance in IOM 5.4.1.4.3 to IOM 5.4.1.4.4 below for

domestic and import reconciliation exams.

5.4.1.4.3 - RECONCILIATION EXAMINATION 

GUIDANCE PART A

Reconciliation examinations are performed to ensure that:

1. The food or cosmetic is what it purports to be

2. There are not unexplained differences in the quantity of 

product ordered, shipped, and received, and

3. There are no signs of tampering or counterfeiting.

Before initiating the exam make a general assessment of 

the appearance of the lot. Look for packaging that: appears 

to have been opened and resealed; appears wet, stained, 

punctured, or powdered. Also, be alert to abnormal 

chemical odors. If any of these conditions are detected stop 

the exam and contact your supervisor for guidance. If the 

lot appears normal proceed with the examination. To the 

extent possible the exam should be performed in a wellventilated, well-lit area.

Determine, to the extent possible, whether:

1. The actual goods in a lot are the same as those that are 

declared in the shipping documents

2. There is consistency in the manufacturer declared on 

the product labeling, bulk product packaging, and 

shipping documents; and

3. There is no (unexplainable) inconsistency in actual 

quantity of goods in the lot, and the quantity ordered and 

declared in the shipping documents.

If no unexplained inconsistencies are detected, no 

further action is indicated.

If unexplainable inconsistencies are detected, document 

the occurrence, including photographs of the labeling and 

packaging, and an accurate count of the lot. Contact your 

supervisor, who should, in the case of imported products, 

contact the U.S. Customs and Border Protection for 

appropriate action. If the examination discloses evidence 

that inaccurate product identification data was submitted to 

the OASIS entry screening system, the program division

should evaluate the need for follow-up with a compliance 

filer evaluation and consider providing the information to the 

U.S. Customs and Border Protection for appropriate action.

In addition, if unexplained inconsistencies are 

detected, follow part B [IOM 5.4.1.4.4] of this guidance 

while conducting a detailed reconciliation exam.

5.4.1.4.4 - RECONCILIATION EXAMINATION 

GUIDANCE PART B

Open the shipping packaging of a quantity of product 

approximating the square root of the number of shipping 

cartons/packages in the lot and examine the contents. Look 

for the following:

1. Product identity on the package that does not match the 

identity declared on the shipping documents

2. Mixed product sizes within a carton or within the lot;

3. Product sizes that do not match the sizes declared on 

the shipping documents

4. Differences in product configuration or package type 

(e.g. plastic containers mixed with glass jars or 

aluminum or steel cans)
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5. Easily apparent variations in weight

6. Product labels that display crude, unprofessional, or 

inconsistent styles of print, color or use of language

7. Unusual placement of labels (e.g. off-center)

8. Variations in lot coding ink color, appearance of 

embossing, or format (e.g., two line vs. three line, use of 

letters, numbers and symbols). unusually excessive use 

of a single code in a very large lot

9. Differences between the actual can codes in the lot and 

those listed on the shipping documents

10.The existence of a tamper-evident notice on the labeling 

when the packaging does not contain a tamper-evident 

feature

11.Product that is beyond its expiration date

12.Inconsistencies in expiration dates within a lot

If no unexplainable discrepancies are noted select at least 

1 package at random from the entire shipment and examine 

their contents. For those products that the contents are 

visible through the package it is not necessary to open the 

package. For other products, open the package and 

examine and field destroy the contents. Look for the 

following:

1. Differences between the product and that which is 

declared on the label

2. Color differences in the product between containers of 

the same lot

3. Style differences in the product between containers of 

the same lot or between the actual product and the label 

and document declaration (e.g., sliced vs. whole, 

colorless noodles vs. egg noodles)

4. Readily detectable abnormal odors (e.g. strong 

decomposition, bitter almond, petroleum odor, garlic, 

chlorine, sulfur). Note: specific sensory examination is 

not expected.

Verification that the product is consistent with the product 

ordered may require that you obtain information from the 

owner of the goods, importer, filer, or custom house broker. 

Review of the following types of documentation may be 

necessary to accomplish the above instructions, to the 

extent that they are available: authentic label supplied by 

the owner of the goods, importer, filer, or custom house 

broker; purchase order; invoice; shipping records (bill of 

lading, weigh bill, manifest). Depending on the findings of 

the exam and record review, you may wish to request that 

the importer assist in an evaluation of the authenticity of the 

product, based on the importer’s experience with the 

product.

Every effort should be made to document any 

discrepancies through use of photographs, and additional 

records that may be available from the filer, importer, 

owner, or customs house broker.

5.4.1.4.5 - SPECIAL SAFETY PRECAUTIONS

See IOM Chapter S - Safety,specifically S.8, S.8.1, S.9, S9.1 through S.9.12. 

When performing an establishment inspection or 

reconciliation examination, follow these instructions:

1. If there are no signs of tampering or counterfeiting, use 

level I protection, which consists of: work gloves; 

coveralls; work boots; and in a dusty situation, a dust 

mask.

2. If there are signs of tampering or counterfeiting, use 

level II protection and consult your supervisor for any 

additional safety precautions needed. Level II protection 

consists of: work gloves worn over surgical gloves; full 

face respirator with appropriate cartridges; disposable 

coveralls; and work boots.

5.4.1.5 - Food Registration

Section 415 of the FD&C Act (21 U.S.C. 350d) requires 

most domestic and foreign facilities that 

manufacture/process, pack, or hold food for human or 

animal consumption in the United States to register with 

FDA before operations commence. Section 415 also 

requires food facilities to renew their registration biennially. 

FDA requires renewals to be submitted between October 1 

and December 31 of each even-numbered year. Facilities 

may register electronically at http://www.access.fda.gov, by 

mail, or by CD-ROM for multiple submissions, to Food and 

Drug Administration, Food Facility Registration, HFS-651, 

5100 Paint Branch Parkway, College Park, MD, 209932, or 

by fax to 301-436-2804. FDA maintains the registration 

information in the Food Facility Registration Module 

(FFRM) within the FDA Unified Registration and Listing 

System (FURLS) database. A facility is not registered until 

all required fields have been completed in FFRM. Upon 

completion, the registrant is issued a system generated 11-

digit registration number.

For food facilities that are required to register, the owner, 

operator, or agent in charge of a facility must provide the 

following:

1. Facility name, address, phone number, and 

emergency contact phone number;

2. Parent company name, address, and phone 

number (if applicable);

3. Name, address, and phone number of the owner, 

operator, or agent in charge;

4. Email address for the contact person of the facility 

or, in the case of a foreign facility, the U.S. agent 

for the facility;

5. All trade names the facility uses;

6. Applicable food product categories, as listed on the 

registration form; 

7. Name, address, and phone number of a foreign 

facility’s U.S. agent and phone number of the 

facility’s emergency contact if it is someone other 

than the U.S. agent; 

8. Certification that the information submitted is true 

and accurate and that the person submitting the 

registration is authorized to do so; and

9. Assurance that FDA will be permitted to inspect the 

facility at the times and in the manner permitted by 

the FD&C Act (section 415(a)(2)).
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Section 415(b) of the FD&C Act also provides FDA with 

authority to suspend the registration of a facility when:

1. FDA determines that food manufactured, 

processed, packed, received, or held by a 

registered facility has a reasonable probability of 

causing serious adverse health consequences or 

death to humans or animals (SAHCODHA); and

2. That facility:

a. Created, caused, or was otherwise 

responsible for that reasonable probability 

of SAHCODHA; or

b. Knew of, or had reason to know of, the 

reasonable probability of SAHCODHA, 

and packed, received, or held such food.

The purpose of registration is to provide FDA with sufficient 

and reliable information about food facilities. Registration 

will help provide information on the origin and distribution of 

food that may be associated with a real and potential threat 

to public health. In the event of a foodborne outbreak of 

illness, registration information will enable FDA to notify the 

food facility representatives and to investigate the source 

and cause of the outbreak. It will also enable FDA to identify 

and contact other facilities that might be associated with 

the food causing the outbreak. 

Under section 301(dd) of the FD&C Act (21 U.S.C. 

331(dd)), the failure to register a food facility is a prohibited 

act. Food from a foreign facility that is not registered may 

be held at the port of entry (section 301(l) of the FD&C Act 

(21 U.S.C. 381(l)).

Low Acid and Acidified Food Registration

21 CFR 108.25(c)(1) and 21 CFR 108.35(c)(1) require all 

commercial processors, when first engaging in the 

manufacture, processing, or packing of acidified foods (AF) 

or low-acid canned Foods (LACF) to register their facility 

with FDA and file information including the name of the 

establishment, principal place of business, the location of 

each establishment in which that processing is carried on, 

the processing method, and a list of foods so processed in 

each establishment by using form FDA 2541.

In addition to registering the facility, AF processors must 

provide FDA with information, using Form FDA 2541e, on 

the scheduled processes for each acidified food in each 

container size (21 CFR 108.25(c)(2)). LACF processors 

must file processes using either Form FDA 2541d, 2541f or 

Form FDA 2541g. 

Both registration and filing can either be done electronically 

(https://www.access.fda.gov/) or by mail by using the 

appropriate forms. 

5.4.1.5.1 – FOOD FACILITY REGISTRATION 

EXEMPTIONS 

The following food facilities do not have to register (21 CFR 

1.226): 

1. A foreign facility, if food from such facility 

undergoes further manufacturing/processing 

(including packaging) by another facility outside the 

U.S. A foreign facility is not exempt under this 

provision if the further manufacturing/processing 

(including packaging) conducted by the 

subsequent facility consists of adding labeling or 

any similar activity of a de minimis nature. The 

facility conducting the de minimis activity also must 

register. 

2. Farms that are devoted to the growing and 

harvesting of crops, the raising of animals 

(including seafood), or both. Washing, trimming of 

outer leaves of, and cooling produce are 

considered part of harvesting. The term “farm” 

includes: 

a. Facilities that pack or hold food, provided that 

all food used in such activities is grown, raised, 

or consumed on that farm or another farm 

under the same ownership; and 

b. Facilities that manufacture/process food, 

provided that all food used in such activities is 

consumed on that farm or another farm under 

the same ownership. 

3. Retail food establishments whose sales to 

consumers exceed their sales to non-consumers 

(businesses are considered non-consumers).

4. Restaurants that prepare and serve food directly to 

consumers for immediate consumption.

5. Nonprofit food establishments in which food is 

prepared for, or served directly to, the consumer.

6. Fishing vessels, including those that not only 

harvest and transport fish but also engage in 

practices such as heading, eviscerating, or freezing 

intended solely to prepare fish for holding on board 

a harvest vessel. However, those fishing vessels 

that otherwise engage in processing fish are 

required to register. For the purposes of this 

section, "processing" means handling, storing, 

preparing, shucking, changing into different market 

forms, manufacturing, preserving, packing, 

labeling, dockside unloading, holding, or heading, 

eviscerating, or freezing other than solely to 

prepare fish for holding on board a harvest vessel. 

7. Facilities that are regulated exclusively, throughout 

the entire facility, by the U.S. Department of 

Agriculture under the Federal Meat Inspection Act 

(21 U.S.C. 601 et seq.), the Poultry Products 

Inspection Act (21 U.S.C. 451 et seq.), or the Egg 

Products Inspection Act (21 U.S.C. 1031 et seq.). 

8. Other exemptions from registration in the final rule 

are based on the definition of food included within 

the scope of the registration regulation. Facilities 

that manufacture/process, pack, or hold food 

contact substances (including packaging 

materials) (21 CFR 1.227(b)(4)(i)(A)) or pesticides 
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(21 CFR 1.227(b)(4)(i)(B)) are exempt from 

registration. 

5.4.1.5.2 - FOOD FACILITY REGISTRATION 

RESOURCES

Additional information relating to food facility registration is 

available at the following website: 

http://www.fda.gov/Food/GuidanceRegulation/FoodFacility

Registration/default.htm. 

See the guidance in Compliance Policy Guide Sec. 

110.300 Registration of Food Facilities Under the Public 

Health Security and Bioterrorism Preparedness and 

Response Act of 2002. 

If a facility (domestic or foreign) is required to register but 

is operating with no registration, a suspended registration, 

an invalid registration, or a cancelled registration, make 

sure that firm’s management is aware of the food facility 

registration requirements, see registration exemptions in 

Section 5.4.1.5.1 - FOOD FACILITY REGISTRATION 

EXEMPTIONS. Inform the firm's management that 

information regarding food facility registration and 

penalties for failure to register is available at the following 

website: 

http://www.fda.gov/Food/GuidanceRegulation/FoodFacility

Registration/default.htm. Encourage electronic registration 

and provide them with the web site address for electronic 

registration http://www.access.fda.gov. Send an email to 

CFSANFoodFacilityRegistration@fda.hhs.gov with FORM000173 with the required fields completed (1-32, 42-48). If 

a facility (domestic or foreign) has a current registration 

but information obtained during the 

inspection/investigation is different from the information in 

FFRM, make sure that firm’s management is aware of the 

food facility registration requirement to submit an update 

to the facility's registration within 60 calendar days of any 

change to any of the required information (21 CFR 

1.234(a)). Inform the firm's management that information 

regarding food facility registration and penalties for failure 

to update their register is available at the following 

website: 

http://www.fda.gov/Food/GuidanceRegulation/FoodFacility

Registration/default.htm. Provide a copy of the Update 

Facility Registration Tutorial located at 

https://www.fda.gov/food/registration-food-facilities-andother-submissions/online-registration-food-facilities. Send 

an email to CFSANFoodFacilityRegistration@fda.hhs.gov 

with FORM-000173 with the required fields completed (1-

32, 42-48) to include an explanation of what firm 

information is different than FFRM. 

Beginning January 4, 2020, an owner, operator, or 

agent in charge of a facility must submit their 

registration to FDA electronically, unless FDA has 

granted a waiver under 21 CFR 1.245 (see 21 CFR 

1.231(a)(2)). If the firm needs to submit a waiver 

request, inform them that they may obtain a 

registration form to complete and submit by mail at 

http://www.fda.gov/downloads/AboutFDA/ReportsMa

nualsForms/Forms/UCM071977.pdf. Also encourage 

the firm to submit the optional information on the 

registration form to assist and facilitate FDA’s future 

communications with the firm.

5.4.2 - PERSONNEL

5.4.2.1 - Management

Follow the guidance described in IOM 5.3.6 when 

documenting individual responsibility including obtaining 

the full name and titles of the following individuals:

1. Owners, partners, or officers.

2. Other management officials or individuals supplying 

information.

3. Individuals to whom credentials were shown and FDA 

482 Notice of Inspection, FDA 482d Request for FSVP 

Records and other inspectional forms issued.

4. Individuals refusing to supply information or permit 

inspection.

5. Individuals with whom inspectional findings were 

discussed or recommendations made.

Regulations require plant management take all reasonable 

measures and precautions to assure control of 

communicable disease, employee cleanliness, appropriate 

training of key personnel, and compliance by all personnel 

with all requirements of 21 CFR 110.10, 112 Subpart C, 

113.10, and 114.10. 

Determine if adequate supervision is provided for critical 

operations where violations are likely to occur if tasks are 

improperly performed.

5.4.2.2 - Employees

Improper employee habits may contribute to violative 

practices in an otherwise satisfactory plant. Observe the 

actions of employees during all phases of the inspection. 

Observe employees at their work stations and determine 

their duties or work functions. 

Note whether employees are following food hygiene and 

food safety practices, including wearing outer garments 

suitable to the operation in a manner that protects against 

allergen cross contact and contamination, maintaining 

adequate personal cleanliness, and store personal items 

properly. Note whether employees eat while on duty. 

Determine if hand washing and sanitizing, if necessary, is 

adequate, and performed at the appropriate times and 

intervals. Unsecured jewelry and other objects should be 

removed, covered or sanitized as appropriate. Gloves, if 

they are used in food handling, shall be maintained in an 

intact, clean, and sanitary condition. Hair nets, headbands, 

caps, beard covers, or other effective hair restraints should 

be worn, where appropriate, in an effective manner.

Determine disease control practices, if there is a 

reasonable possibility of food, food-contact surfaces, or 

food-packaging materials becoming contaminated. For 

example, if employees have an illness, open lesion, 

including boils, sores, or infected wounds, or any other 

abnormal source of microbial contamination, they should be 
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excluded from any operations which may be expected to 

result in contamination.

Under no circumstance should you swab a sore, touch or 

remove a bandage from an employee in an attempt to 

obtain bacteriological data. To do so is a violation of 

personal privacy, possibly hazardous to you and/or the 

employee, and usually provides little useful data.

Observe employee traffic patterns to determine how it 

affects possible routes of contamination. During, 

inspections of produce farms evaluate practices for 

growing, harvesting, packing, and holding practices of 

covered produce to prevent contamination of covered 

produce and food contact surfaces.

Observe and record insanitary employee practices or 

actions showing employees handling or touching insanitary 

or dirty surfaces and then contacting food products or direct 

food contact surfaces. Such practices might include 

employees spitting, handling garbage, placing their hands 

in or near their mouths, cleaning drains, handling dirty 

containers, etc. and then handling food product without 

washing and sanitizing their hands. Observe whether 

employees comply with plant rules such as, "No smoking", 

"Keep doors closed", "Wash hands before returning to 

work", etc. See IOM 5.4.7.2.2.

Be alert to employees handling insanitary objects, then 

quickly dipping their hands in sanitizing solutions without 

first washing them. Depending upon the amount and type 

of filth deposited on the hands during the handling of 

insanitary objects, such attempts at sanitizing are 

questionable at best. Sanitizers work most effectively on 

hands, which have been first cleaned by washing with soap 

and water.

Conversations with employees doing the work may provide 

information on both current and past objectionable 

practices, conditions and circumstances. These should be 

recorded in your notes.

Where appropriate, determine employee education and 

training. Also determine type, duration, and adequacy of 

firm's training programs, if any, to prepare employees for 

their positions and to maintain their skills. 

5.4.3 - PLANTS AND GROUNDS

Grounds must be kept in a condition that will protect against 

the contamination of food. Building structures at produce 

farms may include fully or partially enclosed structures and 

fields. If the plant grounds are bordered by grounds not 

under the operator's control care must be exercised in the 

plant by inspection, extermination, or other means to 

exclude pests, dirt, and filth that may be a source of food 

contamination. Environmental factors such as proximity to 

swamps, rivers, wharves, city dumps, drain fields, runoff, 

concentrated animal feeding operation (CAFO), compost 

operations, manure operations, etc., may contribute to 

rodent, bird, insect or other sanitation problems.

5.4.3.1 - Plant Construction, Design and 

Maintenance

The plant must be suitable in size, construction, and design 

to facilitate maintenance and sanitary operations for foodproduction purposes Determine the approximate size and 

construction (e.g., brick and concrete block) of building 

housing the firm and if suitable in size, construction, and 

design to facilitate maintenance and sanitary operations. 

Buildings, fixtures, and other physical facilities must be 

maintained in a clean and sanitary condition and must be 

kept in repair adequate to prevent food from becoming 

adulterated. Check placement of equipment, storage of 

materials, lighting, ventilation, and placement of partitions 

and screening to eliminate product contamination by 

bacteria, birds, vermin, etc. Determine any construction 

defects or other conditions such as broken windows, 

cracked floor boards, sagging doors, etc. which may permit 

animal entry or harborage.

Determine who is responsible for buildings and grounds 

maintenance. Many facilities such as docks, wharves, or 

other premises are owned and maintained by other firms, 

municipalities, or individuals for lease for manufacturing 

operations. Determine who is legally responsible for 

repairs, maintenance, rodent proofing, screening, etc. 

Evaluate the firm's attitude toward maintenance and 

cleaning operations.

5.4.3.2 - Waste Disposal

Waste and garbage disposal poses a problem in all food 

operations depending upon plant location and municipal 

facilities available.

Check the effectiveness of waste disposal on the premises 

and ensure it does not cause violative conditions or 

contribute toward contamination of the finished products. 

Check for in-plant contamination of equipment and/or 

product, if its water is supplied from nearby streams, 

springs, lakes or wells.

Suspected dumping of sewage effluent into nearby 

streams, lakes, or bay waters near water intakes can be 

documented by color photographs and water-soluble

fluorescein sodium dye. Place approximately two ounces 

dye, which yields a yellowish red color, into the firm's waste 

system and/or toilets, as applicable, and flush the system. 

The discharge area of the effluent becomes readily visible 

by a yellowish-red color on the surface of the water as the 

dye reaches it. Color photographs should be taken.

Determine collecting or flushing methods used to remove 

waste from operating areas. If water is used, determine if it 

is recirculated and thus may contaminate equipment or 

materials.

Determine the disposition of waste materials that should not 

be used as human food such as rancid nuts, juice from 

decomposed tomatoes, etc.
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Determine the disposition of waste, garbage, etc., which 

contain pesticide residues. Determine how this is 

segregated from waste material which contains no 

residues, and which may be used for animal feed.

5.4.3.3 - Plant Services

If applicable, check steam generators for capacity and 

demand. Demand may reach or exceed the rated capacity, 

which could affect adequacy of the process. Check boiler 

water additives if steam comes in direct contact with foods.

Boiler additives for steam that comes into contact with food 

must be approved as direct food additives under 21 CFR 

173.310

Check central compressed air supply for effective removal 

of moisture (condensate) and oil. Determine if any 

undrained loops in the supply line exist where condensate 

can accumulate and become contaminated with foreign 

material or microorganisms.

5.4.4 - RAW MATERIALS

Raw materials and other ingredients must be inspected and 

segregated or otherwise handled as necessary to ascertain 

that they are clean and suitable for processing into food.

Raw materials must be stored under conditions that will 

protect against allergen cross-contact as well as microbial, 

chemical of physical contamination and stored in a manner 

to minimize deterioration. 

List in a general way the nature of raw materials on hand. 

Itemize and describe those, which are unusual to you, or 

involved in a suspected violation (copy quantity of contents 

and ingredient statements, codes, name of manufacturer or 

distributor, etc.). Be alert for additives and preservatives. 

Evaluate the storage of materials. Determine the general 

storage pattern, stock rotation and general housekeeping. 

Materials should be stored so they are accessible for 

inspection. Thoroughly check ceilings, walls, ledges, and 

floors in raw material storage areas for evidence or rodent 

or insect infestation, water dripping or other adverse 

conditions.

5.4.4.1 - Handling Procedure

Determine if growing conditions relative to disease, insects, 

and weather are affecting the raw material. Check 

measures taken for protection against insect or rodent 

damage. Raw materials may be susceptible to 

decomposition, bruising or damage, e.g., soft vegetables 

and fruits delivered in truckload lots. Determine the holding 

times of materials subject to progressive decomposition.

Review storage practices for ingredients that require time / 

temperature control such as bulk silos or in-process batters 

and slurries.

5.4.4.2 - Condition

Evaluate the firm's acceptance examination and inspection 

practices including washing and disposition of rejected lots. 

Examine rejected lots and if you encounter a raw material 

that is potentially adulterated or misbranded, consider 

collecting a sample and ensure the information is reported 

to the appropriate HAF Division. If the documentation 

shows the product was imported, contact your 

corresponding import division to determine if the product 

is subject to Import Alert and to determine appropriate 

follow-up. 

Determine the general acceptability of raw materials for 

their intended use and their effect on the finished product. 

Raw stocks of fruits or vegetables may contribute 

decomposed or filthy material to the finished product. Be 

alert for use of low quality or salvage raw materials. Check 

bags, bales, cases and other types of raw material 

containers to determine signs of abnormal conditions, 

indicating presence of filthy, putrid or decomposed items. 

Check any indication of gnawed or otherwise damaged 

containers, to ascertain if material is violative. Be alert to 

contamination of raw materials by infested or contaminated 

railroad cars or other carriers.

Document by photographs, exhibits or sketches any 

instances where insanitary storage or handling conditions 

exist.

5.4.4.3 - Food Chemicals Codex

Any substance used in foods must be food-grade quality. 

FDA regards the applicable specifications in the current 

edition of the publication "Food Chemicals Codex" as 

establishing food-grade unless FDA publishes other 

specifications in the Federal Register.

Determine whether firm is aware of this publication and 

whether or not they comply.

5.4.5 - EQUIPMENT AND UTENSILS

By arriving before processing begins, you are able to 

evaluate conditions and practices not otherwise observable 

before plant start-up. This includes adequacy of clean-up, 

where and how equipment is stored while not in use, how 

hand sanitizing solutions and food batches are prepared 

and if personnel sanitize their hands and equipment before 

beginning work.

Dirty or improperly cleaned equipment and utensils may be 

the focal point for filth or bacterial contamination of the 

finished product. Examine all equipment and utensils to 

determine the following: design, materials, workmanship, 

materials, maintenance, suitability, and ease of cleaning

and sanitization. Determine if equipment is constructed or 

covered to protect contents from dust and environmental 

contamination. Open inspection ports to check inside only 

when this can be done safely. Notice whether inspection 

ports have been painted over or permanently sealed.

Containers and equipment used to convey or hold human 

food by-products for use as animal food before distribution 

must be designed, constructed of appropriate material, 

cleaned as necessary, and maintained to protect against 
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the contamination of human food by-products for use as 

animal food.

5.4.5.1 - Filtering Systems

Observe the firm's filtering systems and evaluate the 

cleaning methods (or replacement intervals of disposable 

filters) and schedules. Check types of filters used. There 

have been instances where firms have relied on household 

furnace type filters.

5.4.5.2 – Cleaning and Sanitization of 

Equipment and Utensils

Cleaning and sanitizing of utensils and equipment must be 

conducted in a manner that protects against allergen crosscontact and against contamination. Utensils and 

equipment must be cleaned as frequently as necessary to 

protect against allergen cross-contact and against 

contamination of food.

Check the sanitary condition of all machinery. Determine if 

equipment is cleaned prior to each use and the method of 

cleaning. Observe how cleaning occurs and if there is a 

possibility of aerosol contamination of food contact 

surfaces. For example, the use of high-pressure hoses on 

one system that is idle may contaminate an adjacent 

system that is operational. If the firm rents or leases 

equipment on a short-term basis, report prior cleaning 

procedures. Equipment may have been used for pesticides, 

chemicals, drugs, etc., prior to being installed and could 

therefore be a source of cross-contamination.

5.4.5.3 - Conveyor Belt Conditions

Equipment used to convey, hold, or store raw materials and 

other ingredients, work-in-process, rework, or other food 

must be constructed, handled, and maintained during 

manufacturing, processing, packing, and holding in a 

manner that protects against allergen cross-contact and 

against contamination.

Inspect conveyor belts for build-up of residual materials and 

pockets of residue in corners and under belts. Look in 

inspection ports and hard-to-reach places inside, around, 

underneath, and behind equipment and machinery for 

evidence of filth, insects, and/or rodent contamination. 

Chutes and conveyor ducts may appear satisfactory, but a 

rap on them with the heel of your hand or a rubber mallet 

may dislodge static material, which can be examined. See 

IOM 4.3.6.6.3 for procedure on taking In-line Sample Subs.

5.4.5.4 - Utensils

Determine how brushes, scrapers, brooms, and other items 

used during processing or on product contact surfaces are 

cleaned, sanitized and stored. Evaluate the effectiveness 

of the practices observed.

5.4.5.5 - Mercury and Glass Contamination

Be alert for improper placement or inadequately protected 

mercury switches, mercury thermometers, or electric bulbs. 

Breakage of these could spray mercury and glass particles 

onto materials or into processing machinery.

5.4.5.6 - UV Lamps

If firm is using ultra violet (UV) lamps for bacteria control, 

check if it has and uses any method or meters to check the

strength of UV emissions. If so, obtain methods, 

procedures, type equipment used, and schedule for 

replacement of weak UV bulbs.

5.4.5.7 - Chlorine Solution Pipes

In plants where chlorine solution is piped, check on type of 

pipe used. Fiberglass reinforced epoxy pipe has been 

observed to erode inside through the action of the chlorine 

solution. This poses a threat of contamination from exposed 

glass fibers. Pipes made with polyester resin do not 

deteriorate from this solution.

5.4.5.8 - Sanitation Practices

Overall sanitation must be under the supervision of one or 

more competent individuals assigned responsibility for this 

function. Observe sanitizing practices throughout the plant 

and evaluate their effectiveness, degree of supervision 

exercised, strength, time, and methods of use of sanitizing 

agents. Determine the use, or absence of, sanitizing 

solutions both for sanitizing equipment and utensils as well 

as for hand dipping. If chlorine is used, 50 ppm - 200 ppm 

free chlorine should be used for equipment and utensils, 

while a 100-ppm free chlorine will suffice for hand dipping 

solutions. Sanitizing solutions rapidly lose strength with the 

addition of organic material. The strength of the solution 

should be checked several times during the inspection.

Sanitizers including peracetic acid (PAA) and chlorine 

dioxide may be used in post-harvest agriculture water as a 

treatment for bacteria in the water. Ensure any sanitizers 

used are food grade and manufacture’s labeled instructions 

are followed.

5.4.6 - PROCESS AND CONTROLS

All operations must be conducted in accordance with 

adequate sanitation principles. All operations must be 

conducted under such conditions and controls necessary to 

minimize the potential for the growth of microorganisms, 

allergen cross-contact, contamination of food, and 

deterioration of food.

Fans and other air-blowing equipment should operate in a 

manner that minimizes the potential for allergen crosscontact and for contamination. 

Where helpful to describe equipment and processes, draw 

flow plans or diagrams to show movement of materials 

through the plant. Generally, a brief description of each step 
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in the process is sufficient. List all quality control activities 

for each step in the process and identify Preventative 

Control Points. Provide a full description when necessary 

to describe and document objectionable conditions, or 

where the assignment specifically requests it. Observe 

whether hands and equipment are washed or sanitized 

after contact with insanitary surfaces. For example:

1. Workers do general work, then handle the product;

2. Containers contact the floor, then are nested or 

otherwise contact product or table surfaces;

3. Workers use common or dirty clothes or clothing for 

wiping hands;

4. Product falls on a dirty floor or a floor subject to outside 

foot traffic and is returned to the production line.

Be alert for optimum moisture, time and temperature 

conditions conducive to bacterial growth.

Keep in mind that in agricultural practices, some buildings 

may not be fully enclosed. This is a normal part of 

operations and may not indicate insanitary conditions. 

Evaluate the farm’s operations including the process 

controls and cleaning operations.

In industries where scrap portions of the product are reused or re-worked into the process (e.g., candy and 

macaroni products), observe the methods used in the reworking and evaluate from a bacteriological standpoint. Reworking procedures such as soaking of macaroni or noodle 

scrap to soften or hand kneading of scrap material offers an 

excellent seeding medium for bacteria.

When a product is processed in a manner which destroys 

micro-organisms, note whether there are any routes of 

recontamination from the "raw" to the processed product 

(e.g. dusts, common equipment, hands, flies, etc.).

5.4.6.1 - Ingredient Handling

Raw materials and ingredients must be inspected and 

segregated or handled so they are clean and suitable for 

processing and must be stored under conditions that will 

protect against allergen cross-contact and against 

contamination and minimize deterioration. Water reused for 

washing, rinsing, or conveying food must not cause 

allergen cross-contact or increase the level of 

contamination of the food.

All food that has become contaminated to the extent that it 

is adulterated must be rejected, or if appropriate, treated or 

processed to eliminate the contamination.

21 CFR 117.100(b) further prohibits the mixing of a food 

containing defects at levels that render that food 

adulterated with another lot of food. This practice would 

render the final food adulterated, regardless of the defect 

level of the final food.

Material scheduled for rework must be identified and held 

to protect against allergen cross-contact and against 

contamination. This includes holding at proper 

temperatures and relative humidity and in such a manner 

as to prevent the food from becoming adulterated.

Observe the method of adding ingredients to the process. 

Filth may be added into the process stream from dust, 

rodent excreta pellets, debris, etc. adhering to the surface 

of ingredient containers. Evaluate the effectiveness of

cleaning and inspectional operations performed on the 

materials prior to or while adding to the process. Deter-mine 

specific trimming or sorting operations on low quality or 

questionable material. Observe and report any significant

lags during the process or between completion of final 

process and final shipping. For example, excessive delay 

between packing and freezing may be a factor in production 

of a violative product.

5.4.6.2 - Formulas

The Act does not specifically require management to 

furnish formula information except for human drugs, 

restricted devices and infant formulas. Nonetheless, they 

should be requested especially when necessary to 

document violations of standards, labeling, or color and 

food additives. Management may provide the qualitative 

formula but refuse the quantitative formula.

If formula information is refused, attempt to reconstruct 

formula by observing:

1. Product in production,

2. Batch cards or formula sheets,

3. Raw materials and their location.

5.4.6.3 - Food Additives

Refer to the food additives programs in CP (Chapter 9) for 

instructions on conducting establishment inspections of 

firms manufacturing food additive chemicals. Information is 

also available in ORA's "Guide to Inspections of 

Manufacturers of Miscellaneous Food Products - Volume II.

On food inspections, direct your evaluation of food additives 

only to those instances of significant violation, e.g., failure

to declare sulfiting agents on finished product labels, when 

required, or gross misuse.

Routine inspectional coverage will be directed primarily to 

the following two types of additives:

1. Unauthorized and illegal as listed in the Food Additive 

Status List (safrole, thiourea, et al), and

2. Restricted as to amount in finished food.

Because of special problems, exclude the following 

additives from coverage during routine inspections:

1. Packaging materials,

2. Waxes and chemicals applied to fresh fruit and 

vegetables (unless covered under the Produce Safety 

Regulation), 

3. Synthetic flavors and flavoring components except 

those banned by regulations or policy statements (these 

products will be covered under other programs), and
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4. Food additives in feeds (these products will be covered 

under other programs).

Substances Added to Food (formerly The Everything 

Added to Food in the United States (EAFUS) and the Food 

Additives Status List (FASL) found on the CFSAN website 

contains an alphabetical listing of substances, which may 

be added directly to foods or feeds and their status under 

the Food Additives Amendment and Food Standards. In 

addition, a few unauthorized or illegal substances are 

included.

You may encounter substances not included in the Food 

Additives Status List (FASL). Such substances will include:

1. Safe substances not on the list of items Generally 

Recognized as Safe (GRAS) which are not published in 

the regulations, i.e., salt, cane sugar, corn syrup, 

vinegar, etc.;

2. Synthetic flavoring substances because of their 

indefinite status;

3. Substances pending administrative determination,

4. Substances granted prior sanction for specific use prior 

to enactment of the Food Additives Amendment.

Give primary attention to unauthorized substances. 

Document and calculate levels of restricted-use additives in 

finished food only where gross misuse or program 

violations are suspected as follows:

1. List ingredients, which may be restricted substances or 

food additives, and determine their status by referring to 

the current FASL. Document labeling on containers of 

these substances.

2. Obtain the quantitative formula for the finished product 

in question.

3. Determine the total batch weight by converting all 

ingredients to common units.

4. Calculate the theoretical levels in the final product of all 

restricted or unauthorized ingredients from the formula 

by using the Food Additives Nomographs. See IOM 

Exhibit 5-11. 

5. Determine probable level of restricted ingredients by 

observing the weight of each ingredient actually put into 

the batch.

5.4.6.4 - Color Additives

Evaluate the status of color additives observed during each 

establishment inspection by using the Color Additive Status 

List and the Summary of Color Additives Listed in the 

United States in Food, Drugs, Cosmetics, and Medical 

Devices. Both of these links can be found on the CFSAN 

website. These lists provide the current status and use 

limitations of most color additives likely to be found in food, 

drug, device, or cosmetic establishments.

Determine if certified color additives are declared on 

finished product labels, when required.

Stocks of delisted and uncertified colors may be found in 

the possession of manufacturers where there is no 

evidence of misuse. Advise the firm of the status of these 

colors additivies. If management wishes to voluntarily 

destroy such colors additivies, witness the destruction and 

include the facts in your EIR. If the firm declines to destroy 

the colors additivies, determine what disposition is planned, 

i.e., use in non-food, non-drug, non-cosmetic or nonmedical device products. The validity of certification 

information can be checked by accessing the online Color

Certification Database system maintained by the Food and 

Drug Administration, Color Certification Branch. Contact 

the Color Certification Branch to be granted user privilege.

Where decertified or restricted-use colors additivies are 

used in manufacturing food, drug, device, or cosmetics 

products, proceed as follows:

1. Collect an Official Sample consisting of the color

additivies and the article in which it is being used. Make 

every effort to collect interstate shipments of the 

adulterated product before attempting to develop a 

301(k) or 301(a) case. When regulatory action is an 

alternative, obtain sufficient interstate records to cover 

both the color additivies and the basic ingredients of the 

manufactured product. Refer to IOM Sample Schedule, 

Chart 9 - Sampling Schedule for Color Containing 

Products for guidance.

2. Document the use of decertified color additivies after the 

decertifying date. Documentation should include batch 

formula cards, employee statements, code marks 

indicating date of manufacture, color certification 

number, etc. The presence of a color additive in the 

finished product will be confirmed by your servicing 

laboratory.

5.4.6.5 - Quality Control

Appropriate quality control operations must be employed to 

ensure that food is suitable for human consumption and 

that food-packaging materials are safe and suitable. The 

objective of quality control is to ensure the maintenance of 

proper standards in manufactured goods, especially by 

periodic random inspection of the product. Chemical, 

microbial, or extraneous-material testing procedures must 

be used where necessary to identify sanitation failures or 

possible allergen cross-contact and food contamination. 

Your inspection should determine if the firm's quality control 

system accomplishes its intended purpose. 

The manufacturer, processor, packer and holder of food 

must utilize quality control operations that reduce natural or 

unavoidable defects to the lowest defect action level 

currently feasible.

Establish responsibility for specific operations in the control 

system. Determine which quality controls are critical for the 

safety of the finished product. These controls may include 

process control points, sanitation control points, allergen 

control points or other controls intended to ensure a safe 

product is manufactured.
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5.4.6.5.1 - INSPECTION SYSTEM

Determine what inspectional control is exercised over both 

raw materials and the processing steps. Such inspection 

may vary from simple visual or other organoleptic 

examination to elaborate mechanical manipulation and/or 

laboratory tests. Determine what inspection equipment is 

used, i.e., inspection belts, sorting belts, grading tables, 

ultraviolet lights, etc. Ascertain its effectiveness, 

maintenance or adjustment schedules. Where indicated, 

determine the name of the manufacturer of any mechanical 

inspection device and the principles of its operation.

Evaluate the effectiveness of the personnel assigned to 

inspection operations. Determine if the inspection belts or 

pick-out stations are adequately staffed and supervised.

Determine the disposition of waste materials, which are 

unfit for food or feed purposes.

5.4.6.5.2 - LABORATORY TESTS

Describe routine tests or examinations performed by the 

firm's laboratory and the records maintained by the firm.

Tests may include in product testing, finished product 

testing or environmental monitoring. Determine what 

equipment is available in the laboratory and if it is adequate

for the purpose intended. If the firm uses a consulting 

laboratory, determine what tests are performed and how 

often. Review laboratory records for the period immediately 

preceding the inspection.

5.4.6.5.3 - MANUFACTURING CODE SYSTEM

Obtain a complete description of the coding system with 

any necessary keys for interpretation, or the need of ultraviolet light for visibility. (Specific requirements exist for 

codes applied to Low Acid Canned Foods (LACF) and 

Acidified Foods (AF)). Refer to 21 CFR 113.60(c) and 

114.80(b)). 

5.4.6.6 Packaging, Labeling, and Packing

Evaluate packaging, packing and labeling operations. 

“Packaging” is the processes and procedures used to place 

product into its immediate container. “Packing” refers to 

how packages or secondary packages are placed and 

configured for storage, shipping and distribution. 

Evaluate storage of packaging materials including 

protection from contamination by rodents, insects, toxic 

chemicals or other materials. Appraise the manner in which 

containers are handled and delivered to the filling areas. 

Determine if there is likelihood of chipping of glass or 

denting, puncturing, tearing, etc., of packaging materials. 

Observe the preparation of containers prior to filling. 

Consider any washing, steaming, or other cleaning process 

for effectiveness. Determine, in detail, the use of air 

pressure or other cleaning devices.

5.4.6.6.1 - QUANTITY OF CONTENTS

If slack fill is suspected, weigh a representative number of 

finished packages. See IOM 4.3.7 for net weight procedure. 

Sets of official weights are available in the division servicing 

laboratory. These may be used to check the accuracy of 

firm's weighing equipment.

5.4.6.6.2 - LABELING

Check the sanitary condition of labelers and equipment 

feeding cans to, and away from, the labeler. Determine if 

old product is present on any equipment which touches the 

can end seams, in the presence of moisture carry-over from 

the can cooling operation. Check availability of floor drains 

in the labeling area. Absence of floor drains could indicate 

infrequent cleaning of the equipment unless it is physically 

moved to another area for cleaning.

Labeling that identifies the by-product by the common or 

usual name must be affixed to or accompany human food 

by-products for use as animal food when distributed.

Determine what labels are used. Determine what labeling 

accompanies and/or promotes the product, including 

information on the establishment’s internet website. 

Depending upon the claims made in promotional material, 

a food product may be a dietary supplement or drug 

product. Consult your supervisor with questions about 

claims. Obtain specimens of representative labels and 

labeling including pamphlets, booklets, and other 

promotional material as necessary. 

5.4.6.6.3 – NUTRITIONAL AND ALLERGEN

LABELING

If the products contain allergens, ensure that the firm has

controls in place to accurately identify the label declaration

and procedures to ensure proper application to the final

packaging. Review product labels to ensure major food 

allergens are properly declared in the ingredient list or in a 

“Contains” statement. Check for listing of subingredients 

that may contain allergens. See Food Allergen Labeling 

and Consumer Protection Act of 2004 (FALCPA)

requirements for guidance.

For products that bear voluntary gluten-free claims, refer 

to the “Gluten- Free Labeling of Foods” page for guidance. 

Such claims must meet the requirements in the GlutenFree labeling of foods regulation (21 CFR 101.91). 

Refer to the "Industry Resources on the Changes to the 

Nutrition Facts Label” and 21 CFR 101.9 to ensure 

product labels meets the requirement for the Nutrition 

Facts label. 
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5.4.6.6.4 – SANITARY OPERATIONS

Buildings, fixtures, and other physical facilities must be 

maintained in a clean and sanitary condition and must be 

kept in repair adequate to prevent food from becoming 

adulterated.

Substances used in cleaning and sanitizing must be free of 

undesirable microorganisms and be suitable under the 

conditions of use. Toxic compounds, e.g., detergents, 

sanitizers and pesticides, must be properly stored.

Effective measures must be taken to exclude pests from the 

manufacturing, processing, packing, and holding areas and 

to protect against the contamination of food on the 

premises by pests.

5.4.6.6.5 – SANITARY FACILITIES AND CONTROL

Each plant must be equipped with adequate sanitary 

facilities and accommodations including the following: 

water supply, plumbing, sewage disposal, toilet facilities, 

hand washing facilities and rubbish and offal disposal. 

Inspect toilet facilities for cleanliness, adequate supplies of 

toilet paper, soap, towels, hot and cold water, and hand 

washing signs. Check if hand washing facilities are hidden, 

or if located where supervisory personnel can police hand 

washing.

Determine if there is backflow from, or cross connections 

between, piping systems that discharge waste water or 

sewage and piping systems that carry water for food or food 

manufacturing.

5.4.6.6.6 Labeling violations

Refer to 21 CFR part 701 (Cosmetic Labeling) or 21 CFR 

part 740 (warning statements), 21 CFR Part 112 (Produce 

Safety) and applicable sections of CPGM 7329.001 for 

information on labeling requirements. Collect and review 

labels as required by a particular assignment. For routine 

inspections, samples of labels are not required unless 

significant violations are noted.

5.4.6.6.7 Cosmetic product labeling making 

drug claims 

See CPGM 7329.001 (Part III.A. and III.B.1) to determine if 

there is cause to collect evidence supporting that a 

cosmetic is to be considered a drug. Examples of products 

marketed strictly as cosmetics but making drug claims 

include those which claim to promote hair growth, prevent 

baldness, prevent or treat dandruff, enhance eyelash 

growth and treat skin diseases such as acne.

Collect the following as evidence that could enable FDA to 

consider such a product an illegally marketed drug:

1- product labels, including outer containers and all 

inserts

2- promotional material in written and/or electronic 

format

If the product is suspected to contain an active 

pharmaceutical ingredient associated with drug claims also 

collect: 

3- samples of product

4- samples of the active ingredient used in the 

cosmetic and ingredient certificate of analysis

5- records showing usage of the active ingredient in 

manufacturing of a cosmetic product batch

(NOTE: As stated in CPGM 7329.001 III.A, CDER and 

CFSAN have concurrent jurisdiction over any product 

purported as a cosmetic that meets the legal definition of a 

drug.) 

5.4.6.6.8 – QUALIFIED EXEMPT PRODUCE LABELING

When a food packaging label is required on food that would 

otherwise be covered produce it must include prominently 

and conspicuously on the food packaging label the name 

and the complete business address of the farm where the 

produce was grown.

When a food packaging label is not required on food that 

would otherwise be covered produce, it must prominently 

and conspicuously display, at the point of purchase, the 

name and complete business address of the farm where 

the produce was grown, on a label, poster, sign, placard, or 

documents delivered contemporaneously with the produce 

in the normal course of business, or, in the case of Internet 

sales, in an electronic notice.

For additional information on Qualified Exempt produce and 

labeling, refer to 21 CFR 112 Subpart A.

5.4.7 - SANITATION

Documented observation of the conditions under which 

food products are processed, packed, or stored is essential 

to the proper evaluation of the firm's compliance with the 

law. This involves the determination of whether or not 

insanitary conditions contribute to the product being 

adulterated with filth, rendered injurious to health, or 

whether it consists in whole or in part of a filthy, putrid or 

decomposed substance.

Observations that dirt, decomposed materials, feces or 

other filthy materials are present in the facility and there is 

a reasonable possibility these filthy materials will be 

incorporated in the food are also ways of determining 

products may have become contaminated. 
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5.4.7.1 - Routes of Contamination

It is not sufficient to document only the existence of 

insanitary or filthy conditions. You must also demonstrate 

how these conditions contribute or may contribute to 

contaminating the finished product. Investigate and trace 

potential routes of contamination and observe all means by 

which filth or hazardous substance may be incorporated 

into the finished product. For example, defiled molding 

starch in a candy plant may contribute filth to candy passing 

through it, or filth in insect or rodent contaminated raw 

materials may carry over into the finished product. IOM 

Section 4.3.7 contains instructions on sample collection 

techniques for adulteration violations, including instructions 

for field exams and sample collections to document 

evidence of rodent, insect, etc., contaminated lots, and 

instructions for in-line sampling, including bacteriological 

samples. Finished product sample sizes for filth and micro 

collections can be found in the applicable Compliance 

Program (CP) or DDHAFO Inspection Guides.

5.4.7.1.1 - INSECTS

Insect contamination of the finished product may result from 

insect infested raw material, infested processing equipment 

or insanitary practices, and by insanitary handling of the 

finished product. When routes of contamination with insect 

filth are encountered, identify the insects generally, e.g., 

weevils, beetles, moths, etc. If qualified, identify as to 

species. You must be correct in your identification. See IOM 

Appendix A.

5.4.7.1.2 - RODENTS

Rodent contamination of the finished product may result 

from using rodent defiled raw materials, exposure to 

rodents during processing, and by rodent depredation of 

the finished product. When evidence of rodents is

discovered, you should thoroughly describe its 

composition, quantity, estimated age and location. Explain 

its significance and potential for product contamination. 

See IOM Section 4-22– Summary of Sample for Rodent 

Evidence.

5.4.7.1.3 - PESTICIDES

Pesticide contamination of the finished product may be the 

result of mishandling of food products at any stage in

growing, manufacturing or storage. The use of toxic 

rodenticides or insecticides in a manner, which may result 

in contamination, constitutes an insanitary condition. 

Where careless use of these toxic chemicals is observed, 

take photographs and provide other documentation 

showing its significance in relation the food products.

Additional guidance can be found in 21 CFR as follows:

1. Part 117.10(b) - Personnel

2. Part 117.20(b) - Plant Construction and Design

3. Part 117.35(c) - Pest Control

4. Part 117.40(a) - Equipment and Utensils

Additional guidance can be found in 40 CFR Part 180 - 

Tolerances and Exemptions From Tolerances For 

Pesticides in Food Administered by The Environmental 

Protection Agency as follows:

1. Part 180.521 - Fumigants for grain-mill machinery; 

tolerances for residues, and

2. Part 180.522 - Fumigants for processed grains used in 

production of fermented malt beverages; tolerances for 

residues.

Be alert for:

1. Possible PCB contamination. Articles containing PCBs 

(e.g., transformers, PCB containers stored for disposal, 

electrical capacitors) must be marked with prescribed 

labeling to show they contain PCBs. No PCB-containing 

heat exchange fluids, hydraulic fluids or lubricants are 

allowed used in food plants. All PCB storage areas must 

be marked to show the presence of PCBs. Observe food 

plant transformers for possible leakage. If observed, 

determine if food items are stored in the area, and 

sample for PCB contamination. If PCBs are 

encountered in a food establishment, immediately 

advise management this is an objectionable condition 

and advise your supervisor.

2. Possible mix-up of pesticides or industrial chemicals 

with food raw materials.

3. Improperly stored pesticides or industrial chemicals (lids 

open, torn bags in close proximity to foods, signs of 

spillage on floors, pallets, shelves, etc.).

4. Incorrect application methods including excessive use. 

Many pesticide labels give instructions for use and 

precautions on the container.

5. Improper disposal or reuse of pesticide or industrial 

chemical containers.

6. Evidence of tracking powder or improper use of bait 

stations or baited traps.

7. Improper handling of equipment. Movable or motorized 

equipment used for handling possible chemical 

contaminants should not be used for handling food 

products unless they are thoroughly decontaminated. 

For example, fork-lifts moving pallets of pesticides 

should not also be used to move pallets of flour, etc.

8. Use of unauthorized pesticides.

9. Use of foods treated with pesticides and marked "Not 

For Human Consumption" (e.g., Treated seed wheat, 

etc.).

10.Noticeable odor of pesticides.

11.Careless use of machinery lubricants and cleaning 

compounds.

12.Chemical contaminants in incoming water supply.

When inspecting products with a known potential for metals 

contamination, determine whether the firm tests for such 

contamination in raw materials.

Determine who administers the firm's rodent and insect 

control program. Determine responsibility for the careless 

use of toxic materials.
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If pesticide misuse is suspected, obtain the following 

information;

1. Name of exterminator and contract status,

2. Name of pesticide,

3. Name of pesticide manufacturer,

4. EPA registration number,

5. Active ingredients, and

6. Any significant markings on pesticide containers.

Fully document the exact nature of any pesticide or 

industrial chemical contamination noted or suspected. If 

samples are to be collected to document misuse, exercise 

caution to prevent contamination of the immediate area of 

use, product or yourself.

5.4.7.1.4 - OTHER

Contamination of food products by bats, birds and/or other 

animals is possible in facilities where food and roosting 

facilities are available. Examine storage tanks, bins, and 

warehousing areas to determine condition and history of 

use. There have been instances where empty non-food use 

containers were used for food products.

Birds and other animals are normal in a farm operation. 

Evaluate the farm’s wildlife management and their actions 

if there is any contamination or concerns.

5.4.7.2 - Microbiological Concerns

During the inspection, identify likely sources and possible 

routes of contamination of the product with pathogenic 

microorganisms. 

See IOM sections 4.3.6.5 and 4.3.6.6 for sampling 

guidance.

You should become familiar with the flow of the process 

and determine the potential trouble spots, which may be 

built into the operation. To document the establishment is 

operating under insanitary conditions which may result in 

the presence of pathogens in food, it is necessary to show 

that the manufacturing process may have, or has 

contributed to the bacterial load of the product. See IOM 

4.3.7.7 for instructions on sampling for pathogens. If there 

are several products being prepared at once, do not try to 

cover the entire operation during one inspection. Select the 

product which has the greatest potential for bacterial 

contamination or which poses the greatest risk for the 

consumer.

It is extremely important for each EIR to contain complete, 

precise, and detailed descriptions of the entire operation. 

The EIR must be able to stand alone without the analytical 

results, which serve to support the observations.

Observations made during the inspection must be written in 

clear and concise language. The EIR will be reviewed in 

conjunction with analytical results of in-line, environmental 

and finished production samples collected. Based on this 

review and other information which may be available, the 

program division must then decide if the total package will 

support a recommendation for regulatory action.

Each inspection/process will be different, but the 

techniques for gathering the evidence will be the same. 

However, the critical points in the operation should always 

be defined and special attention given to these areas.

Depending on the type of product being produced and the 

process being used, it may be useful to record the time 

each critical step takes, encompassing the entire 

processing period from beginning to end, with correlating 

temperature measurements. This should be done 

especially for products which may support the growth of 

microbial pathogens. During the entire inspection, be aware 

of and document delays in the processing of the product 

(e.g., temperature of product prior to, during and after the 

particular processing step, and the length of time the 

product has been delayed prior to the next step). Also, be 

aware of and document potential routes of environmental 

contamination. 

Some products receive a thermal process at the end of 

production, which may reduce bacterial counts to or near 

zero, although post process contamination is still possible 

through cross-contamination from the environment. Include 

detailed observations of heating step, temperature, length 

of time, controls and documentation used/not used by the 

firm. Even in the presence of end-product thermal 

processing, there is a regulatory significance to insanitary 

conditions prior to cooking, coupled with increases in 

bacterial levels demonstrated through in-line sampling. 

5.4.7.2.1 - PROCESSING EQUIPMENT

Document the addition, or possible addition of pathogenic 

microorganisms from accumulated material due to poorly 

cleaned and/or sanitized processing equipment. All foodcontact surfaces must be cleaned as frequently as 

necessary to protect against allergen cross-contact and 

against contamination of food. 

Observe and report the firm's cleaning and sanitizing

procedures and the condition and cleanliness of food 

contact surfaces before production starts, between 

production runs and at the end of the day. Document any 

residue on food contact surfaces of equipment, especially 

inside complex equipment not easily cleaned and sanitized. 

Report firm’s clean-up procedures in depth, since it may 

lend significance to insanitary conditions of residues on the 

plant machinery which are left to decompose overnight or 

between shifts. Where possible, observe equipment both 

before and after cleaning to assess it adequacy. 

Observations of residues on plant machinery can 

dramatically document the addition of pathogenic 

microorganisms, if present, into the product.

Identify any vectors of contamination (e.g. birds, rodents, 

insects, foot traffic, etc.), and describe sources and the 

routes of contamination from them to the product. Support 

this with your actual observations.
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5.4.7.2.2 - EMPLOYEE PRACTICES

Document any poor employee practice and how they have 

or would provide a route for contaminating the product with 

microorganisms. For example, did employees 

(number/time of day) fail to wash and sanitize their hands 

at the beginning of processing, after breaks, meals, or after 

handling materials likely contaminated with a microbial 

pathogen, etc.; and then handle the finished product. Did 

employees handle product in an insanitary manner (cross 

contaminating raw product with cooked product, etc., how 

many, how often).

5.4.7.3 - Storage

Evaluate the storage of finished products in the same 

manner as for raw materials. Determine if products are 

stored to minimize container abuse, facilitate proper 

rotation, and adherence to the storage requirements. This 

includes refrigeration temperatures, critical temperature 

tolerance, aging of products, and proper disposition of 

distressed stock.

During holding, human food by-products that are destined

for use as animal food must be accurately identified.

5.4.7.3.1 - FOOD TRANSPORT VEHICLES

During food sanitation inspections, (See IOM 5.2.2.2 

regarding issuance of FDA 482, Notice of Inspection while 

inspecting vehicles.), conduct inspections of food transport 

vehicles to include:

1. Evidence of insanitary conditions,

2. Conditions which might lead to food adulteration,

3. Physical defects in the vehicle,

4. Poor industry handling practices.

The following types of transport vehicles should be 

covered:

1. Railroad boxcars, both refrigerated and nonrefrigerated, and hopper cars.

2. Any type of truck used to transport foods; both 

refrigerated and non-refrigerated.

3. Use extreme caution, if it is necessary to inspect tank 

railcars or tank trucks. Usually this coverage will be 

limited to determining what was transported in the tank 

previously and was the tank cleaned and/or sanitized as 

necessary between loads.

4. Vessels used to transport food in I/S commerce. Direct 

coverage primarily to intercoastal type vessels, 

including barges.

5. On farm vehicles used in covered produce activities 

such as trailers, farm trucks, fork lifts, tractors, 

equipment used between growing/harvesting, etc.

Coverage should be limited to food transport vehicles used 

for long haul (I/S) operations. Long haul vehicles are 

defined as those which travel at least 150 miles between 

loading and unloading or which do not return to the point of 

loading at the end of the day.

Regulatory actions are possible if unfit cars are loaded and, 

as a result of loading, adulteration occurs. Fully document 

any violations noted with appropriate samples and 

photographs. When vehicle insanitation is observed, it is 

imperative the carrier's and shipper's responsibility for the 

food adulteration be documented by appropriate evidence 

development, such as:

1. The nature and extent of the conditions or practices, and

2. The mechanical or construction defects associated with 

the food transport vehicle.

3. Individual responsibility for vehicle or trailer cleaning, 

vehicle assignments, load assignments, etc.

If gathering evidence about a single carrier, seek a series 

of occurrences at numerous locations involving as many 

different shippers as possible.

Basically, two types of vehicles will be covered.

5.4.7.3.2 - VEHICLES AT RECEIVERS

When inspecting receivers of food products, examine the 

food transport vehicle prior to or during unloading. Make a 

preliminary assessment of food product condition, then 

inspect the vehicle after unloading to determine its 

condition and whether the unloaded food may have been 

contaminated during shipment. If the food appears to have 

been adulterated, collect a sample(s) for regulatory 

consideration. Samples collected from vehicles, which 

have moved the product in interstate commerce are official 

samples. You may also collect Documentary (DOC) 

Samples from the vehicle to substantiate the route of 

contamination.

5.4.7.3.3 - VEHICLES AT SHIPPERS

When inspecting shippers of food products, examine the 

food transport vehicle just prior to loading to determine its 

sanitary/structural conditions. If the vehicle has significant 

sanitation or structural deficiencies, notify the shipper of 

these conditions and of the possibility of product 

adulteration. If the shipper loads food aboard the vehicle, 

alert your supervisor so he/she can contact the FDA 

program division where the consignee is located for 

possible follow-up. You may also collect samples from the 

load. These samples will become official when the Bill of 

Lading is issued.

5.4.8 - DISTRIBUTION

Report the general distribution pattern of the firm. Review 

interstate shipping records or invoices to report shipment of 

specific lots. If access to invoices or shipping records is not 

possible, observe shipping cartons, loading areas, order 

rooms, address stencils, railroad cars on sidings, etc., to 

determine customer names, addresses and destination of 

shipments. If no products are suspect, obtain a listing of the 

firm's larger consignees.
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5.4.8.1 - Promotion and Advertising

Determine the methods used to promote products and how 

the products reach the ultimate consumer. Determine what 

printed promotional materials are used and whether they 

accompany the products or are distributed under a 

separate promotional scheme. Check on the possibility of 

oral representations, i.e., door-to-door salesmen, spieler, 

etc. and obtain copies of brochures, pamphlets, tearsheets, 

instructions to salespersons, etc. Where indicated, obtain 

the lecture schedule of any promotional lecture program. If 

applicable, determine the general pattern of the media used 

for promotion and advertising.

5.4.8.2 - Recall Procedure

Determine the firm's recall procedure. Audit enough 

records to determine the effectiveness of established 

procedures. Firms that are subject to Preventative Controls 

have specific requirements for recall plan. Refer to 21 CFR 

117.139. 

Note: Produce farms are not required to have a recall 

procedure.

5.4.8.3 - Complaint Files

Review the firm's complaint files. Where possible, copy the 

names and addresses of representative complainants; 

include a brief summary of each significant complaint in the 

EIR.

During the inspection, identify who reviews complaints and 

their qualifications. Describe the criteria used by the firm in 

evaluating the significance of complaints and how they are 

investigated. Determine if records are kept of oral and 

telephone complaints. See IOM 5.2.8 for discussion of 

complaints with management and IOM 5.11.4.3.11 for 

reporting of complaints in the EIR.

Complaints may not be filed in one specific file, but may be 

scattered throughout various files under other subject titles 

including Product name; Customer name; Injured party 

name; Adjustment File; Customer Relations; Repair orders, 

etc. 

During the inspection investigate all complaints received by 

FDA since the last inspections, or that were not covered 

during the previous inspection. See IOM 5.2.8, 5.4.1.1 and 

5.11.4.3.11. Complaints can be accessed by clicking on the 

Consumer Complaint link in FMS, or by clicking the “Firm 

360” link in OSAR.

5.4.9 - OTHER GOVERNMENT INSPECTION

See IOM 3.1 for general procedures on cooperating with 

other Federal, State, and local officials.

During Establishment Inspections determine the specific 

type of inspection service and inspecting units, which cover 

the firm, such as the name of the federal, state, county, or 

city health agency or department. Obtain the name and title 

of the inspectional official, and general method of operation.

5.4.9.1 - Federal

Do not inspect firms, or those portions of the plant, subject 

to compulsory, continuous inspection under USDA's Meat 

Inspection Act, Poultry Products Inspection Act, or Egg 

Products Inspection Act, except on specific instructions 

from your supervisor or assignment document.

Ingredients or manufacturing processes common to both 

USDA and FDA regulated products should be inspected by 

FDA. See IOM 3.2.1.4 for FDA-USDA Agreements in 

specific areas.

Provide routine FDA coverage of such firms as breweries 

and wineries, which may be intermittently inspected on a 

compulsory basis by the U.S. Treasury Department, U.S. 

Public Health Service, or other agencies.

All products inspected under the voluntary inspection 

service of the Agriculture Marketing Service (AMS), USDA, 

and the National Marine Fisheries Service (NMFS), US 

Department of Commerce, are subject to FDA jurisdiction 

and are usually given routine coverage. However, formal 

written Agreements or Memoranda of Understanding 

between FDA and other agencies are often executed and 

may govern the agreeing agencies' operations on this type

of inspected plants. When assigned this type of plant for 

inspection, always check to see if an Agreement or a 

Memorandum of Understanding exists between FDA and 

the agency involved to determine the obligations of both 

agencies. See IOM 3.1.2.1 and 3.2.

If you are assigned to cover a Federally Inspected plant 

which is under either compulsory or voluntary inspection, 

present your credentials and an FDA 482 Notice of 

Inspection to management and:

1. Identify yourself to the inspector(s) and invite him/her to 

accompany you on the inspection but do not insist on 

their participation.

2. At the conclusion of the inspection, offer to discuss your 

observations and provide the in-plant inspector with a 

copy of your Inspectional Observations (FDA 483).

5.4.9.2 - State and Local

State and local officials usually have extensive regulatory 

authority over firms in their area regardless of the interstate 

movement or origin of the food products involved. Joint 

FDA-State or local inspections are frequently conducted. 

These are usually arranged by program division

administrative or supervisory personnel. See IOM 3.1.2 and 

3.3.

5.4.9.3 - Grade A Dairy Plant Inspections

If you are assigned to conduct an inspection or sample 

collection at a milk plant that is covered under the Grade A

Milk program, which has milk and milk products labeled and 

sold as Grade A, you should verify the need to complete 
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the assignment with your supervisor and the Milk Specialist. 

Grade A milk plants, milk, and milk products labeled as 

Grade A are inspected by state inspectors and check rated 

by FDA's Milk Specialists and you should not inspect these

Grade A milk and milk products. Milk plants in the Grade A 

Milk program and covered by the Interstate Milk Shippers 

(IMS) program are identified in the Interstate Milk Shippers 

List of Sanitation Compliance and Enforcement Ratings. 

This reference lists the specific milk plant and each milk and 

milk product covered under the IMS program. These Grade 

A milk and milk products are covered by a MOU between 

the FDA and the states, which places primary inspectional 

responsibility with the state.

There are situations where you will need to conduct an 

inspection in a Grade A milk plant and cover products they 

manufacture which do not carry the "Grade A" designation 

(such as juices). Fluid milk and milk products, cultured/

acidified milk and milk products, eggnog, cream(s) sour 

cream, and yogurt are all considered Grade A and are 

required to be labeled as Grade A. The Grade A milk plant 

may also manufacture milk and milk products which are 

optional for the Grade A designation, depending upon the 

particular state. Cottage cheese is considered a Grade A 

optional milk product. If the state does not require the 

Grade A designation for cottage cheese, then the cottage 

cheese will not be included in the IMS listing of Grade A 

milk and milk products for that specific milk plant. Also, if 

the Grade A milk plant is manufacturing condensed or dried 

milk or milk products or condensed or dried whey or whey 

products, which are optionally labeled as Grade A, then 

those milk or milk products must be IMS listed and are 

covered under the Grade A Milk Program. Note: This same 

Grade A milk plant may also be manufacturing non-Grade 

A versions of these condensed/dried milk or milk products 

or condensed/dried whey or whey products. 

5.4.10 - FOOD STANDARDS

The Federal Food, Drug, and Cosmetic Act requires the 

Secretary of Health and Human Services to promulgate 

reasonable definitions and Standards for food to promote 

honesty and fair dealing in the interest of consumers. When 

a Standard becomes effective, it establishes the common 

or usual name for the article, defines the article and fixes its 

standard of identity. It is then the official specification for the 

food. The food industry actively participates in the 

development of a Standard and supplies much of the data 

upon which the regulation is based.

The Food Standards (FS) Inspection is made to obtain data 

for use, together with information from other sources in 

developing a Food Standard. Food Standard inspections 

are also made to determine a firm's compliance with food 

standards regulations, when manufacturing a standardized 

food.

5.4.10.1 - Food STANDARDS Inspection

Food Standard (FS) inspection assignments usually 

originate from CFSAN. When an inspection is planned for 

the purpose of collecting data to support a proposed food 

standard regulation, the program division may elect to 

advise the firm, if the CFSAN has not already done so. If 

the firm selected does not choose to cooperate, it may be 

necessary to visit additional plants in order to obtain the 

desired information. Selection of additional firms should be 

done in consultation with the CFSAN.

Some firms often contend their entire process and formulas 

are "trade secrets". Attempt to persuade management the 

term "trade secret" should only be used to cover the 

process and/or quantitative-qualitative formulation which is 

truly unique to the firm. In instances where the firm is 

reluctant to release any of the information requested, point 

out FDA will, within the limits of the Freedom of Information 

Act, make every effort to preserve the confidentiality of the 

composition, make-up, and production levels of the product 

through the use of codes, which cannot be traced back to 

the firm. Include as much of the compositional and 

processing information as you can in the body of the report, 

without violating the firm's confidence.

5.4.10.2 - Food Inspection Report

FS EIR's may be used as exhibits at public hearings and 

are subject to review by any interested party.

Three copies of the report are prepared. The original and 

one copy will be submitted to the CFSAN and one copy kept 

for the program division file. Sign the original and duplicates 

of the first and last pages of each report sent to the Center.

Divide the report into three sections.

5.4.10.2.1 - ESTABLISHMENT INSPECTION 

RECORD (EI RECORD)

In order to relate the sections of the report to each other 

and to any assignments, and to assure any parts of the 

reports made public will not be identified as to the name of 

the firm or individuals therein, each program division will set 

up a master list of numbers. One number will be assigned 

to each establishment covered, e.g., "BLT FS-3". For each 

FS Inspection place the assigned number next to the firm 

name on the EI Record. All other pages of the report shall 

be identified only by this number, the name of the 

commodity, and date. Example: "EIR Frozen Fish Sticks 

10-3-87 BLT FS-3". This indicates a FS EI of frozen fish 

sticks conducted by Baltimore OHAFO Division 2E on 10-

3-87 in a plant designated as #3.

Where a producer may be reluctant to release any of the 

information requested, point out the FDA will, within the 

limits of the FOIA, make every effort to preserve the 

confidentiality of the composition, make-up, and production 

levels of his product through the use of codes, which cannot 

be traced back to the firm.
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5.4.10.2.2 - BODY OF REPORT

Prepare the body of the report following the narrative 

outline as for any other food EIR except for the restrictions 

below.

The body of the FS report should also contain information 

in regard to the approximate annual value and volume as 

well as the percent of interstate business for each product 

covered. This is necessary because the coversheet, which 

contains this information, identifies the firm and will not be 

made public. Processes and the listing of raw materials 

used by the firm, which are not restricted by the term "trade 

secret" should be included. Any opinions, 

recommendations, or other information obtained or offered 

by individuals interviewed should be reported. Any 

suggestions made by individuals interviewed regarding 

what should be placed in the Standards for the products 

covered should be included. All individuals interviewed, firm 

name, etc. should have an identifying code assigned.

The body of the report should not include names and titles 

of individuals, (including USDA, USDI, or other inspectors), 

trade secret information, labeling, trade names, formulas, 

sample numbers, firm name or location of plant (other than 

by state or region), shipments, or other distribution 

information, legal status, or regulatory history. This 

information will be placed in the "Special Information" 

section of the report.

5.4.10.2.3 - SPECIAL INFORMATION 

SECTION

This is a separate attachment to the EIR which lists the 

names and titles of individuals (including other government 

inspectors) and firms with a reference code for each. The 

EIR should refer only to "Mr. A.," "Mr. B.," "Firm X," "Firm 

Y", etc. Do not use the firm or individual's actual initials in 

the body of the report. Include all information excluded from 

the body of the report and mount all labels obtained during 

the EI Labels may be quoted in the body of the report, but 

do not identify the firm. List the "Special Information Sheet" 

in the FACTS endorsement section as an enclosure.

Supplemental Reports - If, because of an additional visit or 

visits to the same firm on the same project, it is necessary 

to prepare another EIR, flag the report with the same 

number as assigned to the original report. For example, 

mark the EI Record "BLT FS-3 Supplemental Report", and 

the remaining pages, "EIR Frozen Fish Sticks 10-25-87 

BLT FS-3 Supplemental Report."

5.4.10.3 - Violative Inspections

When an inspection made in connection with the Food 

Standards project shows insanitary or other conditions 

which are not germane to the assignment or in the Program 

division's opinion suggests regulatory action, an 

appropriate narrative of the violative conditions should be 

prepared as a Regulatory Addendum. 

5.4.12 - PESTICIDES

5.4.12.1 - Pesticide Inspections

The objective of a Pesticide Inspection is to determine the 

likelihood of excessive residues of significant pesticides in 

or on products in consumer channels, and to develop 

sources of information for uncovering improper use of 

pesticide chemicals.

This requires directing coverage to two major areas:

1. Pesticide practices in the production and processing of 

field crops.

2. Application of pesticide chemicals in establishments 

storing and processing raw agricultural products.

Pesticide coverage must be provided during all food 

establishment inspections. Coverage of raw agricultural 

products will generally be on a growing-area basis.

Problem areas include:

1. Improper use of pesticides around animals - gross 

misuse of sprays and dips in animal husbandry may 

result in pesticide residues in foods.

2. Use of contaminated animal feeds - waste and spent 

materials from processing operations may contain 

heavy concentrations of pesticide residues, which were 

present in the original commodity. See Compliance 

Policy Guide 575.100. 

3. Past pesticide usage - past pesticide practices on 

growing fields. Past use of persistent pesticides may 

result in excessive residues in the current food crop. 

You may need to check on pesticide usage for several 

years prior to an incident to ensure you gather enough 

information. Some pesticides last for many years in the 

environment.

5.4.12.2 - Current Practices

Cooperative Activities - important sources of information 

relative to evaluating the "Pesticide Environment" include:

1. At the start of the growing season, spray schedules 

recommended for each crop by county agents, state 

experiment stations, large pesticide dealers, farmers 

cooperatives, et al should be obtained.

2. Visits to agricultural advisors may provide information 

relative to heavy infestation of insect pests and fungal 

infections on specific crops in specific areas.

3. Daily radio broadcasts in most agricultural areas may 

provide information on spray schedules, insect pests, 

harvesting and shipping locations, etc.

4. Field employees of fruit and vegetable canning and 

freezing plants usually recommend spray schedules, 

pesticides, and harvesting schedules for products 

produced by contract growers.

5. United States Weather Bureau Offices and their reports 

will provide data on weather conditions, which may 

affect insect growth and their development, size of fruit 

or leaf growth, and dissipation of pesticide chemicals.
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6. USDA Market News Service daily price quotations, and 

weekly quotations in trade magazines provide 

information regarding harvesting schedules since 

market prices are indicators of how quickly a crop will be 

harvested in a given area. Growers who have the 

opportunity to obtain high prices may harvest their crops 

without regard to recommended pre-harvest intervals.

7. State Colleges of Agriculture seminars or short courses 

on food and vegetable production may alert you to 

significant departures from usual agricultural practices. 

Prior approval to attend such meetings should be 

secured from your supervisor.

8. Pesticide suppliers and distributors may provide 

information on spray practices, schedules, and the 

name and address of growers, etc.

NOTE: The U.S. Department of Agriculture has a Pesticide 

Data Program (PDP), which provides data on pesticide use 

and residue detection. This program helps form the basis 

for conducting realistic dietary risk assessments and 

evaluating pesticide tolerances. Coordination of this 

program is multi-departmental, involving USDA, EPA and 

FDA, covered by a MOU (Federal Cooperative Agreements 

Manual). As a part of this program USDA collects data on 

agricultural chemical usage, and factors influencing 

chemical use, and collects pesticide residue data through 

cooperation with nine participating states. USDA provides 

this data to EPA, FDA and the public. Several USDA 

publications are listed below as reference material. 

The contact point at USDA for pesticide residue matters is:

Martha Lamont, Director

Monitoring Program Office, Science Division

Agricultural Marketing Service, USDA

8609 Sudley Road, Suite 206

Manassas, VA 20110

703-330-2300

Reference materials - the following reference materials 

provide background and data necessary or helpful in 

evaluating current practices. This material should be 

available at the program division office.

1. Pesticide Chemicals - Regulations under the Federal 

Food, Drug and Cosmetic Act on tolerances for 

pesticides in food administered by the Environmental 

Protection Agency (EPA). 

2. EPA's Pesticide Regulations - Tolerances for Raw 

Agriculture Products. (See 40 CFR 180) 

3. EPA's Rebuttable Presumption Against Registration 

(RPAR) List.

4. Pesticide Index. - By William J. Wiswesser. A 

publication containing information on trade names, 

composition and uses of commercial pesticide 

formulations.

5. The Daily Summary or Weekly Summary. News 

releases and reports from USDA.

6. USDA's Weekly Summary Shipments-Unloads.

7. Agricultural Economic Report No. 717 Pesticide and 

Fertilizer Use and Trends in U.S. Agriculture (May 1995)

8. Annual Pesticide Data Summary

9. Reports from USDA's Crop Reporting Board.

10.USDA's Pesticide Assessment Reports.

5.4.12.3 - Growers

Preliminary investigation of growing areas at the start of the 

season will provide data necessary for program division

work planning including production schedules, types and 

acreage of crops, pesticides used and the names and 

addresses of growers and shippers. The Produce Safety 

Network (PSN) can be of assistance in obtaining some of 

this information.

Growing Dates - The significant growing dates relative to 

pesticide usage are as follows:

1. Planting date,

2. Date of full bloom, and

3. Date of edible parts formation.

Harvest Dates - The dates of the anticipated harvest 

season will provide planning information relative to preharvest application and shipping.

Acreage - This will provide volume information for work 

planning.

5.4.12.3.1 - PESTICIDE APPLICATION

Ascertain the actual pesticide application pattern for each 

crop. Look for objective evidence to document actual 

grower practice. Check the grower's supply of pesticide 

chemicals, look for used pesticide containers, visit his 

source of supply, etc. Check spraying and dusting 

practices. Establish if pesticide chemicals are used in such 

a manner that excessive residues might result.

The following information provides a basis for evaluating 

pesticide usage:

1. Pesticide Chemical Applied - List the common name if 

there is no doubt as to the chemical identity of the 

pesticide. Include labeling indications and instructions.

2. Method of Application - Describe the method of 

application i.e., ground rig, airplane, greenhouse 

aerosol, hand, etc.

3. Formulation - Describe the formulation i.e., wettable 

powder, emulsifiable concentrate, dust, granules, 

aerosol, etc. Express as pounds of active ingredient per 

gallon or percent wettable powder.

4. Number of Applications and Dates.

5. Rate of Last Application - Calculate the amount of active 

ingredient per acre.

6. Pre-Harvest Interval (PHI) - Calculate the number of 

days between the day of the last application of pesticide 

and the harvest date or anticipated harvest date. 

Compare to the PHI.

7. Visible residue on grower's crop.

8. Summary of Usage - Determine the USDA Summary 

Limitations and evaluate the responsible usage.

5.4.12.3.2 - PESTICIDE MISUSE/DRIFT/SOIL 

CONTAMINATION

Pesticide residues, which exceed established tolerances, 

action levels, or "regulatory analytical limits”, may be 

caused by pesticide misuse which can include:
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1. Excessive application of a chemical on a permitted crop.

2. Failure to follow labeled time intervals between the last 

pesticide application and harvest.

3. Use of a non-approved pesticide on a crop.

4. Failure to wash a crop when pesticide labeling requires 

it (e.g., for certain EBDC's).

Other conditions, which may cause illegal residues, include 

spray drift and soil contamination.

Drift may be documented by determining which crops and 

pesticides have been grown/used in fields adjacent to those 

sampled. Determine direction of prevailing winds and wind 

condition on the day of spraying. Selective sampling will aid 

in determining if drift occurred. Compliance Samples 

collected to document pesticide drift should be Flagged as 

a Pesticide Sample and noted in the Remarks section of the 

CR as "Drift Sample - Maintain as Individual Subs".

Soil contamination by compounds, which are relatively 

stable in the environment, may cause systemic uptake of 

the compounds by growing crops. Follow-up investigations 

to violative samples may, in some limited cases, include soil 

samples as an attempt to determine the source of the 

contaminant. Do not routinely collect soil samples.

5.4.12.4 - Packers and Shippers

Follow the same general procedure as in IOM 5.4.12.3. 

Observe and report the following:

1. Treatment Before Shipping - This may include stripping 

of leaves, washing, vacuum cooling, application of postharvest preservative chemicals, use of cartons with 

mold-inhibiting chemicals, waxes, colors, fumigation, 

etc.

2. Identification of Growers' Lots - Determine procedure or 

methods used to maintain the identity of each grower's 

lot. Provide the code and key if any.

3. Labeling - Quote labeling or brand names.

4. Responsibility - Determine whether the packer or 

shipper knows what sprays have been used on the 

products shipped.

5.4.12.5 - Pesticide Suppliers

Pesticide suppliers should be visited routinely during 

growing-area coverage. They may provide valuable 

information about pesticides being used on various crops in 

the growing area. Some suppliers may suggest spray 

schedules or advise growers about pesticide usage.

Determine what representations were made by the 

manufacturer of pesticide chemicals for which there is only 

a temporary tolerance or experimental permit. Get copies 

of any correspondence relating to sale and use of these 

products. Obtain names of growers to whom sales are 

made if such sale was not for use on acreage assigned 

under the experimental permit. Collect Official Samples of 

any crops treated with the pesticide.

5.4.12.6 - Pesticide Applicators

Pesticide applicators may provide valuable information 

about pesticides being used on various crops in the growing 

area. Interview several pesticide applicators, particularly 

those using airborne equipment. Determine the pesticide 

chemicals, their formulation, and on what crops they are 

currently being applied. Determine who supplies the 

pesticides and how they are prepared to assure proper 

concentration. If state law requires the applicator to keep a 

record of each spray application, request permission to 

review such records. Determine what steps are taken to 

assure drift on adjoining crops does not result in violative 

residues. Where there is likelihood of drift, collect Selective 

Samples from adjoining fields.

5.4.12.7 - Sample Collections

See IOM Sample Schedule Chart 3 - Pesticides.

5.4.13 – COSMETIC INSPECTIONS

There is no FDA pre-approval for cosmetic products or 

ingredients, with the exception of color additives. However, 

cosmetic firms are responsible for marketing safe and 

properly labeled products. Inspections can identify 

adulterated and misbranded cosmetics as defined in 

Sections 601 and 602, respectively, of the Food Drug and 

Cosmetic Act. Inspections cover three major areas:

1- Control of processes and quality of products -

Products are manufactured in an adequate state of 

control to meet the firm’s established quality 

standards.

2- Sanitation, cleanliness and hygiene – The facility is 

clean and orderly, sanitary conditions are being 

maintained and workers are attentive to preventing 

contamination

3- Labeling – Products are labeled in compliance with 

regulations and are accurately labeled to reflect 

contents

FDA inspections can reveal use of prohibited ingredients, 

noncompliance with requirements related to color additives, 

failure to adhere to requirements for tamper-resistant 

packaging where needed, and violations involving labeling 

without necessarily performing an on-site inspection. 

Assurance of cosmetic product safety also depends upon 

control of microbiological product quality during 

manufacturing and distribution of products. An on-site 

inspection is the only means by which FDA can determine 

if cosmetics are being manufactured under insanitary 

conditions whereby cosmetics may be contaminated with 

objectionable microorganisms. (See 5.4.13.3 

(Contaminated Cosmetics) and 5.4.13.5 (Specific Types of 

Cosmetic Safety Concerns))

5.4.13.1 Preparation and References

Refer to this section and the Compliance Program Manual 

titled “Cosmetics Program: Import and Domestic” (CPGM 

7329.001) when performing a cosmetic site inspection. 
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Refer to any direction from CFSAN or the district having to 

do with a concern about a particular product. Refer to the 

sections 5.1, 5.2, 5.3, 5.4.1.1, 5.4.6.1.1, 5.4.6.6.4, in the 

IOM, and read or be familiar with all pertinent references 

provided in this subchapter (5.4.13). Be familiar with the 

statutory requirements and definitions and parts of the 

Code of Federal Regulations Title 21 (21 CFR) applicable 

to cosmetics. For more background information on 

cosmetic site inspections see Inspection of Cosmetics. 

Related Resources:

• Cosmetics Compliance Program: Import and 

Domestic (PDF 310 KB) (CPGM 7329.001) 

• GMP Draft Guidance for Industry: Cosmetic Good 

Manufacturing Practices 

• Import Alerts for Cosmetics 

5.4.13.2 – Documents and Records 

While there is no requirement for the firm to provide records 

for your review, it is important to review documents and 

records, to determine if the site has adequate procedures 

and systems for manufacturing and monitoring to ensure 

production and distribution of safe cosmetic products. 

Therefore, make a request to review processing records, 

packaging and labeling records, raw material records and 

any records pertinent to the manufacture, packaging, 

labeling and distribution of the cosmetic product, including 

finished product testing, batch release, complaints and/or 

adverse events. 

5.4.13.3- Contaminated Cosmetics 

Inspect the firm’s methods for preventing and controlling 

microbial and other forms of contamination and review 

records that may indicate batches that were manufactured 

and distributed in violation of any of the cosmetic 

adulteration provisions of the Act. 

Typical causes of product adulteration are manufacturing 

under insanitary conditions, improper storage conditions 

and product design flaws and/or defects (i.e., ingredients, 

packaging) including use of an ineffective preservative 

system (see below). Observe and document when any of 

the following present a potential cause of insanitary 

conditions: 

1- Overall cleanliness of the facility and sanitation 

practices (including programs and systems for pest 

control and waste disposal)

2- Personal hygiene and employee health (including 

training of staff and monitoring of employees by 

supervision)

3- Handling of ingredients, materials and products by

employees (including procedures for making 

transfers, training and use of PPE)

4- Microbiological quality of ingredients (including 

whether ingredient batches received from suppliers 

are tested by the manufacturer and how 

ingredients are stored) (see next section on raw 

material quality)

5- Water systems (including system design and 

control and monitoring of microbiological quality)

6- Equipment design (including potential for stagnant 

water)

7- Cleaning and sanitization of equipment surfaces 

contacting process stream or products (including 

utensils and shared equipment)

8- Buildup of previous batches of material on 

equipment surfaces during prolonged 

manufacturing campaigns

Susceptibility of cosmetic products to microbiological 

growth is governed the by water activity of the formulation. 

Preservatives are added to mitigate the risk of microbial 

growth, but each preservative system’s capability has 

unique limitations. As proof of effectiveness of 

preservation, the formulation can be subjected to microbial 

challenge testing. Check to see if the manufacturer (or 

product distributor) has performed and retained 

documentation of preservative efficacy testing on its 

cosmetic product formulations. See CPGM 7329.001 

section on Adequacy of Preservation for more information. 

Also refer to preceding sections 5.4.7.1 and 5.4.7.2 for 

more information about documenting routes of 

contamination and microbiological concerns.

See CPGM 7329.001 Part V.1.c. for more information on 

current policy on microbiological quality of cosmetics, 

including products and levels of concern constituting 

potential health hazard.

5.4.13.4- Cosmetic Ingredients

Determine if the manufacturer has suitable procedures for 

supplier selection and qualification and adequate controls 

for chemical, microbial and physical contamination to 

ensure the ingredients are suitable for use in cosmetics. If 

the manufacturer uses ingredients that have been 

reconditioned or reprocessed, determine if there is 

adequate documentation to justify such use. Determine 

who (e.g. the firm’s quality department, the product 

distributor) decides to approve suppliers, and accept or 

reject ingredient batches from suppliers. Determine if 

ingredients (and packaging materials) are stored and 

handled properly to prevent mix-up and contamination; 

and if there are suitable systems to identify and trace 

ingredients and packaging materials used in cosmetic 

products. 

5.4.13.5 – Specific Types of Product Safety 

Concerns

You should be aware of certain cosmetic products that 

CFSAN/OCAC has identified as posing unusual safety 

hazards due to concerns about the product ingredients. 

Examples include:

1- tattoo inks

2- ingredients or products labeled “organic” or 

“natural”

3- products lacking traditional preservatives

4- products containing stem cells or human tissue

5- wet wipes (used by infants/children and adults)
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6- cosmetic non-alcohol oral care products

7- eye area products 

8- potential use by immuno-suppressed or 

institutionalized individuals 

There are currently no prohibitions on the use of many of 

these ingredients and FDA’s regulatory policy is still in 

development. OCAC will provide training on these specific 

topics and others that may emerge in the future. If in doubt 

about the status of a particular ingredient or type of product 

you encounter on an inspection, contact CFSAN/OCAC. 

5.4.14 – Foreign Supplier Verification 

Program

See Subchapter 6.8 Foreign Supplier Verification Program 

for inspectional instructions.

SUBCHAPTER 5.5 - DRUGS

5.5.1 - DRUG INSPECTIONS

Authority for inspection is discussed in IOM 2.2. FD&C Act 

Sections 501(a)-(d) and 501(j) [21 U.S.C. 351(a)-(d), (j)] 

describe the ways in which a drug may be or may become 

adulterated. Section 502 of the FD&C Act [21 U.S.C. 352] 

does the same, with respect to misbranding. Section 505 of 

the FD&C Act [21 U.S.C. 355] requires that new drugs be 

approved by FDA. Therefore, the purposes of a drug 

inspection are:

1. To evaluate a firm's adherence to the concepts of 

sanitation and good manufacturing practice; i.e., 

production and control procedures include all 

reasonable precautions to ensure the identity, strength, 

quality, and purity of the finished products;

2. To identify deficiencies that could lead to the 

manufacturing and distribution of products in violation of 

the Act, e.g., non-conformance with Official Compendia, 

super/sub potency, substitution;

3. To determine whether a firm is distributing drugs that 

lack required FDA approval including counterfeit or 

diverted drugs;

4. To obtain correction of those deficiencies;

5. To determine if drugs are manufactured by the same 

procedures and formulations as specified in the Drug 

Application documents;

6. To determine the drug labeling and promotional 

practices of the firm;

7. To ensure the firm is reporting NDA field alerts as 

required by 21 CFR 314.81 and Biological Product 

Deviation Reports (BPDRs) for therapeutic biological 

products as required by 21 CFR 600.14; 

8. To determine if the firm is complying with the 

requirements of the Prescription Drug Marketing Act 

(PDMA) and regulations; and

9. To determine the disposition of Drug Quality Reports 

(DQRS) received from the Drug Surveillance and Data 

Reporting Branch (DSDRB)/CDER; and

10.To determine if the firm is complying with post market

Adverse Drug Experience reporting requirements as 

required by 21 CFR sections 310.305 (prescription 

drugs without approved NDA/ANDA), 314.80, 314.98, 

and 314.540 (application drug products), and 600.80

(therapeutic biological products), and Section 760 of the 

FD&C Act (non-application nonprescription products) 

[21 U.S.C. 379aa]. 

11.For pharmacy compounding inspections determine if 

compounded drug products meet the conditions of 

section 503A or 503B of the FDCA

5.5.1.1 - Preparation and References

Become familiar with current programs related to drugs. 

Determine the nature of the assignment, i.e., a specific drug 

problem or a routine inspection, and if necessary, consult 

other program division personnel, such as chemists, 

microbiologists, etc., or center personnel, such as office of 

compliance staff. Review the establishment program 

division files of the firm to be inspected including:

1. Establishment Inspection Reports,

2. Firm Profiles,

3. OTC monographs and other pertinent references for 

non-application products,

4. Drug Applications (New, Abbreviated and 

Investigational) and the Knowledge Transfer Memo, if 

the Center has provided it for a specific pre-approval 

inspection, 

5. Therapeutic Biologics License Applications, 

6. Sample results,

7. Complaints and Recalls,

8. Regulatory files,

9. Drug Quality Reports (DQRs), NDA Field Alert Reports 

(FARs), and Biological Product Deviation Reports 

(BPDRs),

10.Drug Registration and Listing

11.Facility Dossier where applicable 

12.Inspection Assignment memo where applicable.

During this review identify products which:

1. Are difficult to manufacture,

2. Are complex dosage forms,

3. Require special tests or assays, or cannot be assayed,

4. Require special processes or equipment,

5. Are new drugs and/or potent low dosage drugs, 

Are misbranded, unapproved, fraudulent, or are 

compounded human drug products that do not meet the 

conditions of section 503A or 503B of the FDCA 

Review the factory jacket, FACTS OEI and 

registration/listing data, and all complaint reports which are 

marked follow-up next inspection. These complaints are to 

be investigated during the inspection and discussed with 

management. See IOM 5.2.7.

Become familiar with current regulations and programs 

relating to drugs, CP 7356.002, et al. When making GMP 

inspections, discuss with your supervisor the advisability of 

using a microbiologist, analyst, engineer, or other technical 

personnel to aid in evaluating those areas of the firm 
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germane to their expertise. Review the FD&C Act, Chapter 

V, Drugs and Devices. Review parts of 21 CFR 210/211

applicable to the inspection involved and Bioavailability (21 

CFR 320). In the case of APIs, review FD&C Act section 

501(a)(2)(B) [21 U.S.C 351(a)(2)(B)] and the ICH industry 

guideline entitled "Q7 Good Manufacturing Practice

Guidance for Active Pharmaceutical Ingredients."

Review the current editions of the United States 

Pharmacopeia (USP), and Remington's Pharmaceutical 

Sciences for information on specific products or dosage 

forms. See IOM 1.10.3 for special regulatory information by 

product category.

Review 21 CFR 203 "Prescription Drug Marketing", 21 CFR 

205 "Guidelines for State Licensing of Rx Drug 

Distributors", and CP 7356.022, Enforcement of the 

Prescription Drug Marketing Act (PDMA).

Before conducting drug preapproval inspections (CP 

7346.832) it is important to be familiar with the application 

and coordinate accomplishment of Center goals 

communicated by (1) inspectional memos, (2) preinspection briefings, and/or (3) Center participation on the 

inspection team.

The Office of Manufacturing Quality (OMQ) in CDER has 

established two mechanisms for you to obtain technical 

assistance before, during, or after an inspection:

1. Office of Manufacturing Quality (OMQ). This webpage

contains organizational charts, names and phone 

numbers of OMQ individuals identified as technical 

specialists in various areas.

2. Questions and Answers on Current Good 

Manufacturing Practices for Drugs. This forum is 

intended to provide timely answers to questions about 

the meaning and application of CGMPs for human, 

animal, and biological drugs, and to share these widely. 

These questions and answers generally clarify 

statements of existing requirements or policy.

5.5.1.2 - Inspectional Approach

Follow Compliance Program Guidance Manual (CPGM) 

7356.002 and others as appropriate when conducting drug 

CGMP inspections. In-depth inspection of all manufacturing 

and control operations is usually not feasible or practical. A 

risk-based systems audit approach is recommended in 

which higher risk, therapeutically significant, medically 

necessary and difficult to manufacture drugs are covered in 

greater detail during an inspection. (Note: The status of a 

drug as medically necessary is determined by CDER. For 

information, contact Office of Compliance/Recalls and 

Shortages Branch via email at cderrecalls@fda.hhs.gov) 

The latter group includes, but is not limited to, time release 

and low dose products, metered dose aerosols, aseptically 

processed drugs, and formulations with components that 

are not freely soluble. If the inspection is conducted for 

CDER- led combination product, see also IOM 5.12.

CPGM 7356.002 incorporates the systems-based 

approach to conducting an inspection and identifies six (6) 

systems in a drug establishment for inspection: Quality, 

Facilities and Equipment, Materials, Production, Packaging 

and Labeling and Laboratory Control Systems. The full 

inspection option includes coverage of at least four (4) of 

the systems; the abbreviated inspection option covers of at 

least two (2) systems. In both cases, CPGM 7356.002, 

indicates the Quality System be selected as one of the 

systems being covered. During the evaluation of the Quality 

System it is important to determine if top management 

makes science-based decisions and acts promptly to 

identify, investigate, correct, and prevent manufacturing 

problems likely to, or have led to, product quality problems.

When inspecting drug manufacturers marketing a number 

of drugs meeting the risk criteria, the following may help you 

identify suspect products:

1. Reviewing the firm's complaint files early in the 

inspection to determine relative numbers of complaints 

per product.

2. Inspecting the quarantine, returned, reprocessed, 

and/or rejected product storage areas to identify 

rejected product.

3. Identifying those products which have process control 

problems and batch rejections via review of processing 

trends and examining reviews performed under 21 CFR 

211.180(e).

4. Reviewing summaries of laboratory data (e.g., 

laboratory workbooks), OOS investigations, and 

laboratory deviation reports.

5.5.2 - DRUG REGISTRATION & LISTING

Registration and listing is required whether or not interstate 

commerce is involved. See Exhibit 5-12 and IOM 2.9.1.1 for 

additional information.

Two or more companies occupying the same premises and 

having interlocking management are considered one 

establishment and usually will be assigned a single 

registration number. See IOM 5.1.1.11 - Multiple 

Occupancy Inspections for additional information.

Independent laboratories providing analytical or other 

laboratory control services on commercially marketed 

drugs must register.

FACTS will indicate if the establishment is registered for the 

current year. If you determine registration and listing is 

required, advise your supervisor. After checking for past 

registration, cancellation, etc., the program division will 

provide the firm with the proper forms and instructions.

Each establishment is required to list with FDA every drug 

in commercial distribution, whether or not the output of such 

establishment or any particular drug so listed enters 

interstate commerce. During the establishment inspection, 

you should remind the firm of its responsibilities for 

ensuring its drug listing accurately reflects the current 

product line and updating its listing as necessary to include 

all product changes, NDC changes, and discontinuations in 

accordance with 21 CFR 207. If registration and listing 
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deficiencies are found, document it in your EIR, collect a 

documentary sample and/or contact your supervisor. 

5.5.3 - PROMOTION AND ADVERTISING

21 CFR 202.1 which pertains only to prescription drugs, 

covers advertisements in published journals, magazines, 

other periodicals, and newspapers, and advertisements 

broadcast through media such as radio, television, and 

telephone communication systems. Determine what 

department or individual is responsible for promotion and 

advertising and how this responsibility is demonstrated. 

Ascertain what media (radio, television, newspapers, trade 

journals, etc.) are utilized to promote products.

Do not routinely collect examples of current advertising. 

Advertising should be collected only on assignment, or if, in 

your opinion, it is clearly in violation of Section 502(n) of the 

FD&C Act [21 U.S.C. 352 (n)] or 21 CFR 202.1.

5.5.4 - GUARANTEES AND LABELING 

AGREEMENTS

Determine the firm's policies relative to receiving 

guarantees for raw materials and issuing guarantees on 

their products. Also determine firm's practices regarding 

shipment of unlabeled drugs under labeling agreements. 

See IOM 5.3.7.2.

5.5.5 - OTHER INSPECTIONAL ISSUES

5.5.5.1 - Intended Use

Please see the discussion of jurisdiction in section IOM 

5.11.4.3.6.

5.5.5.2 - Drug Approval Status

The investigator should ascertain whether the drugs 

manufactured by the firm are covered by an NDA, ANDA, 

NADA, ANADA, OTC monograph, or marketed under a 

claim of DESI or another exemption status. 

5.5.5.3 – Drug Status Questions

If you have questions about misbranding, new drug status,

API/finished drug product status, drug/cosmetic, or 

drug/food (dietary supplement) status, , contact the Office 

of Unapproved Drugs and Labeling Compliance in CDER’s 

Office of Compliance at 301-796-3100 or 

CDEROUDLCPMTRACK@CDER.FDA.GOV. 

If you have questions about the status of compounded 

human drugs products, contact the the Office of 

Compounding Quality Compliance in CDER’s Office of 

Compliance at 301-796-3100 or 

Compounding@fda.hhs.gov. 

5.5.5.4 – Verification of Compliance with 

PDMA Requirements

The investigator should ascertain whether a manufacturer

uses samples of prescription drugs to market their 

products. If so, they need to comply with the regulations at 

21 CFR 203 Subpart D – Samples. Refer to CPGM program 

7356.022, ENFORCEMENT OF THE DRUG SAMPLE 

DISTRIBUTION REQUIREMENTS OF THE 

PRESCRIPTION DRUG MARKETING ACT (PDMA). If you 

have questions concerning this portion of an inspection, 

contact the Office of Compliance at 301-796-3100 or 

DrugSupplyChainIntegrity@fda.hhs.gov. 

5.5.5.5 - Drug/Dietary Supplement Status

In instances where the drug/dietary supplement status of a 

product is unclear, the investigator should collect all related 

labeling and promotional materials including pertinent 

Internet web sites. This labeling and promotional material 

is often useful in determining the intended use of a product 

(See 21 CFR 201.128). Labeling, promotional materials 

and Internet web sites often contain information, for 

example, disease claims, that can be used to determine the 

intended use of a product and thereby if it is a dietary 

supplement or a drug and an unapproved new drug.

5.5.5.6 - Approved Drugs

Check the current programs in your CPGM, Section 505 of 

the FD&C Act [21 U.S.C. 355] and 21 CFR part 314 for 

required information. You may ask your designated preapproval manager for CMC information of the targeted drug 

application. You may take the program division’s copy of 

the NDA into the plant as a reference during the inspection. 

Document and report all deviations from representations in 

the NDA even though they may appear to be minor.

5.5.5.7 - Investigational Drugs

Follow the instructions in pertinent programs in your CPGM

or as indicated in the specific assignment received.

5.5.5.8 - Clinical Investigators and/or Clinical 

Pharmacologists

Inspections in this area will be on specific assignment 

previously cleared by the Administration. Follow guidance 

in the CPGM or assignment.

5.5.5.9 – Delaying, Denying, Limiting or 

Refusing Drug Inspections

Use reasonable discretion when discerning whether action 

taken by a drug firm during an inspection constitutes 

delaying, denying, limiting, or refusing drug inspection. If 

you are unsure whether an action taken by a firm 

constitutes delaying, denying, limiting, or refusing drug 

inspection, contact your supervisor.
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As needed, refer to the Guidance for Industry – 

Circumstances that Constitute Delaying, Denying, 

Limiting, or Refusing a Drug Inspection, for examples of 

firm actions that may cause a drug to be deemed 

adulterated under FD&C Act section 501(j). Remember, 

however, that these examples are not exhaustive, and that 

guidance documents do not establish legally enforceable 

rights or responsibilities and are not legally binding on the 

firm or the agency. See IOM 1.10.1.

5.5.8 - DRUG INSPECTION REPORT

See IOM 1.1 English language requirement. The 

requirements in IOM 5.11.4.3, and any applicable 

Compliance Program Guidance Manuals can be used to 

help you prepare your report.

This does not cover the reporting requirements for a 

directed inspection with a narrow focus, such as a 

complaint follow-up or investigation into a recall. In those 

cases, use your judgment and guidance in IOM 5.11.4 

about the depth of reporting required. Follow the 

instructions and format for a human drug inspection report 

as contained in IOM 5.11.4.2 and 5.11.4.3.

The human drug inspection report does not require full and 

detailed narratives for every area for every inspection. The 

firm's state of compliance, the previous inspectional report 

and information, complexity of operations and other 

aspects all are determinants in how much reporting will be 

necessary. In many cases, brief summaries addressing the 

format areas will be sufficient.

SUBCHAPTER 5.6 - DEVICES

5.6.1 - DEVICE INSPECTIONS

See IOM 2.2 for discussion of statutory authority.

The term "device" is defined in Sec. 201(h) of the FD&C Act

[21 U.S.C. 321 (h)]. In-vitro diagnostics (21 CFR 809) are 

devices, as defined in 201(h) of the Act [21 U.S.C. 321 (h)], 

and may also be biological products subject to Section 351 

of the PHS Act. 

Inspections involving devices should be made only by those 

individuals qualified by training and experience in the 

device area. Electronic product radiation is defined in 21 

CFR 1000. Because of the specific nature of inspections 

and investigations involving radiation, only personnel who 

have special training in this field should be assigned such 

work. However, others may participate for training 

purposes. Specific Compliance Program Guidance 

Manuals designate the type of individual and special 

training required for work in these areas.

CAUTION: Radiation-emitting devices and substances 

present a unique hazard and risk potential. Every effort 

should be taken to prevent any undue exposure or 

contamination. Monitoring devices must be used whenever 

radiation exposure is possible. Investigators should also be 

on the alert for, and avoid contact with, manufacturing 

materials and hazards associated with the manufacturing 

of many types of devices, which may present a threat to 

health, e.g., ethylene oxide, high voltage, pathogenic 

biomaterials, etc. See IOM Chapter S. Specifically, S.15.2- 

Radiation Hazards, S.12.6.3 - Ethylene Oxide (EtO), and 

S.15.1.3 - Energy Hazards.

5.6.1.1 - Technical Assistance

Each program divisions have engineers and radiological 

health personnel available for technical assistance and 

consultation. Do not hesitate to make use of their services.

Engineers, quality assurance specialists, and national 

expert investigators in OMPTO as well as in OHAFO are 

available for on-site consultation and assistance in problem 

areas. Refer to FMD-142. The subject matter experts are 

also available by telephone for consultation and to answer 

questions regarding regulation and program interpretation 

and QS/GMP application. Additionally, the CDRH Office of 

Health Technologies, within the Office of Product Quality

(organized by device product) can be contacted as 

necessary.

WEAC has various personnel (biomedical, sterility, 

electronic, materials, mechanical, nuclear and plastics 

engineers) available for telephone consultation and on-site 

assistance at 781-756-9700. 

5.6.1.2 - Sample Collection During Inspection

Because of the limited funds available for samples and the 

relatively high cost of device samples, it is essential you 

consider, in consultation with your supervisor, the following 

factors before collecting a physical sample of a device:

1. If follow-up to a QS/GMP deviation, will sampling 

demonstrate the deviation and/or a defective product? 

Documentary Samples may be more suitable for 

QS/GMP purposes.

2. Likelihood of the analysis showing the device is unfit for 

its intended use.

3. Samples costing over $250.00.

4. Laboratory capability to analyze the sample. See IOM 

4-24 for sample routing information.

If you are still uncertain, discuss with your supervisor and 

contact the CDRH Laboratory or WEAC 781-756-9700 for 

assistance.

Contact CDRH for assistance as follows:

In-vitro Diagnostic Devices - Office of Science and 

Engineering Laboratories (HFZ-113).

NOTE: Device samples do not require 702(b) portions. 

Include in the FDA 525 and with the C/R, if destined for 

different locations, a copy of the firm's finished device 

specifications, test methods and acceptance and/or 

rejection criteria.
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5.6.1.3 - Types of Inspections

General device inspections will be conducted under various 

Compliance Programs found in the Compliance Program 

Guidance Manual. The majority of these will be QS/GMP 

inspections, but often the reason for the inspection will vary. 

For example, inspections may be conducted to assist the 

pre-market clearance process (PMA or Class III 510(k)), to 

specifically address MDR concerns, or to assure in-depth 

coverage of an aspect of manufacturing (sterility). The 

following describes some of these inspections.If the 

inspection is conducted for CDRH- led combination product 

see also IOM 5.12.

5.6.2 - MEDICAL DEVICE QUALITY SYSTEM/ 

GOOD MANUFACTURING PRACTICES

Section 520(f) of the FD&C Act [21 U.S.C. 360j(f)] provides 

the Agency with authority to prescribe regulations requiring 

that the methods used in, and the facilities and controls 

used for, the manufacture, packing, storage, and 

installation of medical devices conform to good 

manufacturing practices. The medical device Quality 

System/Good Manufacturing Practices Regulation 

(QS/GMP)(21 CFR 820) became effective on June 1, 1997.

21 CFR 820 is established and promulgated under the 

authority of Sections 501, 502, 510, 513, 514, 515, 518, 

519, 520, 522, 701, 704, 801 and 803 of the FD&C Act (21 

U.S.C. 351, 352, 360, 360c, 360d, 360e, 360h, 360i, 360j, 

360l, 371, 374, 381 and 383). Failure to comply with the 

provisions of 21 CFR 820 renders a device adulterated 

under Section 501(h) of the FD&C Act [21 U.S.C. 351(h)].

The regulations promulgated under 21 CFR 820 establish 

minimum requirements applicable to finished devices, as 

defined in 820.1(a). This regulation is not intended to apply 

to manufacturers of components or parts of finished 

devices, but instead recommended to them as a guide. In 

some special cases, components have been classified as 

finished devices (dental resins, alloys, etc.) and are subject 

to the QS/GMP. Manufacturers of human blood and blood 

components are not subject to this part, but are subject to 

21 CFR 606. 

The QS/GMP includes regulations regarding Purchasing 

Controls, 21 CFR 820.50, Receiving, In-process and 

Finished Device Acceptance, 21 CFR 820.80, and 

Traceability, 21 CFR 820.65, that require finished device 

manufacturers exercise more control over the components 

they use in their devices. The preamble of the QS/GMP 

states: "Since FDA is not regulating component suppliers, 

FDA believes that the explicit addition to the CGMP 

requirements of the purchasing controls...is necessary to 

provide the additional assurance that only acceptable 

components are used." And "...inspections and tests, and 

other verification tools, are also an important part of 

ensuring that components and finished devices conform to 

approved specifications." It further states, "...traceability of 

components must be maintained so potential and actual 

problem components can be traced back to the supplier."

The medical device QS/GMP is an umbrella GMP that 

specifies general objectives rather than methods. It is left to 

the manufacturer to develop the best methods to meet 

these objectives. You must use good judgment in 

determining compliance with the QS/GMP, keeping in mind 

that it is an umbrella GMP and all requirements may not 

apply or be necessary. The purpose of the QS/GMP is to 

assure conformance to specifications and to ensure that all 

requirements that will contribute to assuring the finished 

device meets specifications are implemented. You should 

not insist that a manufacturer meet non-applicable 

requirements. Refer to IOM Exhibit 5-13 for types of 

establishments that are required to comply with the 

QS/GMP.

5.6.2.1 - Pre-Inspectional Activities

Prior to the start of any medical device inspection, the 

factory jacket or establishment history of the establishment 

should be reviewed. You should review the previous 

inspectional findings and subsequent correspondence 

between the establishment and FDA; any MDR or 

consumer complaints where it was determined follow-up 

would occur at the next inspection; and any notifications of 

recalls since the last inspection.

MDR data most useful in preparing for an inspection 

includes specific MDRs for the manufacturer (i.e., query by 

establishment's short name) for the time frame since the 

last inspection, or MDRs for the generic devices 

manufactured by that establishment (i.e., query by product 

code) for some reasonable time frame. This data assists 

you in determining potential problem areas in the 

manufacture or design of the device, or lot or batch specific 

issues. MDR information can be accessed through the 

Total Product Lifecycle Reports (TPLC). A medical device 

report data request may be submitted to Office of Health 

Technologies, within the Office of Product Quality. The 

agency's Voluntary Malfunction Summary Reporting 

Program grants an alternative that permits manufacturer 

reporting of certain device malfunction MDRs in summary 

form on a quarterly basis. For general questions regarding 

MDR reporting requirements, contact the MDR Team at 

MDRPolicy@fda.hhs.gov. 

The establishment's reported registration and listing data 

should be verified during any GMP inspection to assure 

there have been no changes and the registration and listing 

data is accurately reported. 

510(k) and PMA data assists you in determining what 

devices the establishment is manufacturing and whether 

any new devices have been designed or changed since the 

last inspection. This data is useful in focusing the inspection 

on new or changed devices as well as devices that are 

higher risk devices, i.e., Class II or III versus Class I. This 

information can be accessed through IMAGE 2000 plus and 

TPLC.

Since information about medical device firms is distributed 

in many different databases, CDRH information is pulled 

into Total Product Life Cycle (TPLC) reports and ORA 
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created Establishment History Reports (EHR1). EHR1 

Reports combine detailed recall and inspection history 

information. TPLC Reports combine registration and 

listing, premarket, adverse event (MDR), and CDRH 

complaint details as well as high level recall and inspection 

information. ORA investigators can run these reports in 

order to prepare for inspections. 

It is necessary to have access to both Business Objects 

and ORADSS in order to run EHR1 and TPLC reports. If 

you require access, send a request to the Employee 

Resource & Information Center (ERIC). You need to 

specify in your request to ERIC that you need access to the 

TPLC reports. 

Accessing EHR1 reports

Go to 

http://inside.fda.gov:9003/it/Applications/ORAApplicati

ons/default.htm

Under ORADSS click go

Click the Documents Tab; then click Folders 

Navigate (by hitting the plus sign) into Public Folders 

and then the Domestic Reports subfolder

Double click on the Establishment History Report 

subfolder

Select EHR1 and double click

*Note: For initial inspections, there will not be any 

inspection history in the EHR1 report

Accessing TPLC reports

Go to. BI launch pad (fda.gov)

In the upper left corner, there aretabs labeled “Home” 

and “Documents”. Click on “Documents”. At the bottom 

left, are tabs labeled “My Documents”, “Folders”, 

“Categories” and “Search”. Click on “Folders”. Find 

folder that is labeled “Public Folders”. Click on the 

folder. Navigate (by hitting the plus sign) on CDRH and 

then into the TPLC. The TPLC reports will appear to the 

right. Select a report by double clicking the report 

name

Beneficial reports include:

• TPLC Manufacturer Name – displays 

information on a firm based on the 

Manufacturer name entered. The 

manufacturer name entered must be in upper 

case as the reports are case sensitive. Since 

company names vary with the inclusion of 

commas, abbreviations (INC vs. INC. vs. 

INCORPORATED), or division names, it is 

best to first use the shortest name possible with 

a wild card character (%). For example, to 

search for “XYZ SURGICAL CO (PVT) LTD”, it 

would be best to first use “XYZ%”. This will 

return all manufacturers that have a name 

beginning with that phrase. Given that some 

firms might have similar names, the report 

might return several companies with a name 

beginning with “XYZ”. The best option then is 

to look at those companies returned in the 

report and modify the name used in the search. 

• TPLC Product Code Reviewer - displays 

information on one or more specific product 

codes entered. Ensure that the product codes 

entered are in upper case as the reports are 

case sensitive.

For general questions or for help accessing this

information, contact your CDRH Regulatory Inspections

and Audits Team (RIAT) or OMDRHO Operations at

ORADeviceInspectionPOC@fda.hhs.gov.

Firm participation in the Medical Device Single Audit

Program (MDSAP) must be verified by accessing the 

MDSAP Master List before conducting routine 

medical device inspections. MDSAP participating 

firms are not subject to FDA routine device

inspections. Verificationshould be performed by 

searching the list for both firm name and address. If

additional verification is required by contacting an

MDSAP subject matter experts (SMEs) via email at

MDSAP@fda.hhs.gov.

When the reason for an inspection at a firm participating in 

MDSAP is not routine (e.g. for-cause, EPRC) alert CDRH 

RIAT of the planned inspection by sending an e-mail to 

MDSAP@fda.hhs.gov prior to scheduling the inspection, if 

possible, but no later than five business days before the 

scheduled inspection. The e-mail should include the 

name, address, and FEI of the firm, the type of inspection 

that will be performed, the estimated inspection dates, 

and any additional information pertinent to the situation, 

such as a reference number for a Warning Letter. This 

allows the FDA MDSAP SMEs to be aware of ORA followup activities in the event the firm challenges FDA on the 

need for an inspection. 

 

If the reason for an inspection at an MDSAP participating 

firm is related to a specific assignment, generated by either 

ORA or CDRH, the ORA Division should email ORA 

OMDRHO Operations at 

ORADeviceInspectionPOC@fda.hhs.gov at least ten days 

prior to initiating the inspection The email should contain 

the name and FEI of the firm, the nature of the complaint or 

quality issue, and any other relevant firm/device information 

prior to ORA investigators conducting the inspection or 

investigation. In these situations, a teleconference between 

the FDA CDRH MDSAP SMEs and ORA may be needed to 

discuss the scope of any planned inspection or 

investigationand allow additional information to be 

exchanged between CDRH and ORA.   

IOM 5.2 should be followed in regards to preannouncement of medical device inspections.
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5.6.2.2 - Quality Audit

The inspectional approach for identifying inadequate 

auditing of a quality assurance program is limited by the 

agency's policy, which prohibits access to audit results. The 

policy is stated in CPG section 130.300 (7151.02). Under 

the QS/GMP regulation (21 CFR 820.180 (c)) this 

prohibition extends to evaluations or audits of suppliers, 21 

CFR 820.50(a), and Management Reviews conducted per 

21 CFR 820.20. Evidence of inadequate auditing may be 

discovered without gaining access to the written audit 

reports. See the Guide to Inspections of Medical Device 

Manufacturers or Guide to Inspections of Quality Systems 

for inspectional guidance.

The preamble to the QS/GMP specifically states, "FDA will 

review the corrective and preventive action procedures and 

activities performed in conformance with those procedures 

without reviewing the internal audit reports. FDA wants to 

make it clear that corrective and preventive actions, to 

include the documentation of these activities, which result 

from internal audits and management reviews are not 

covered under the exemption at 820.180(c)." Therefore, 

these corrective and preventive actions and documentation 

are not excepted from inspectional scrutiny.

The QS/GMP regulation (21 CFR 820.180(c)) requires a 

manufacturer to certify in writing that audits and reaudits 

have been conducted whenever requested to do so by an 

investigator. Investigators through their supervisors should 

consult with CDRH Office of Regulatory Programs (HFZ320) prior to requesting such certification.

5.6.2.3 - Records

FDA has distinct authority under section 704(e) of the 

FD&C Act [21 U.S.C. 374 (e)] to inspect and copy records 

required under section 519 or 520(g) of the FD&C Act [21 

U.S.C. 360i or 360j (g)]. Investigators should only collect 

copies of documents as necessary to support observations 

or to satisfy assignments. Manufacturers who have 

petitioned for and obtained exemption from the QS/GMP 

are not exempted from FDA authority to review and copy 

complaints and records associated with investigation of 

device failures and complaints.

You may advise manufacturers they may mark as 

confidential those records they deem proprietary to aid FDA 

in determining which information may be disclosed under 

Freedom of Information Act. 

Records must be maintained for as long as necessary to 

facilitate evaluation of any report of adverse performance, 

but not less than two years from the date the device is 

released for distribution. Records required by the Radiation 

Control for Health and Safety Act must be maintained for 

five years. It is permissible to retain records in electronic or 

photocopy form, providing the copies are true and accurate 

reproductions.

5.6.2.4 - Complaint Files

Complaints are written or oral expressions of dissatisfaction 

with finished device identity, quality, durability, reliability, 

safety, effectiveness or performance. Routine requests for 

service would not normally be considered complaints. 

However, service requests should be reviewed to detect 

complaints, and as part of any trend analysis system, and 

to comply with 820.200(a)(3).

FDA has the authority to require a device firm to open its 

complaint files, and review and copy documents from the 

file.

Provisions in the FD&C Act pertaining to FDA review of 

records are:

1. For restricted devices the FD&C Act in Section 

704(a)(1)(B) [21 U.S.C. 374 (a)(1)(B)] extends 

inspection authority to records, files, papers, processes, 

controls and facilities bearing on restricted medical 

devices. See FD&C Act Sec. 704 [21 U.S.C. 374] for a 

full explanation and for a list of the items, e.g., financial 

data, which are exempt from disclosure to FDA.

2. For all devices, including restricted devices, refer to 

Section 704(e) of the FD&C Act [21 U.S.C. 374 (e)], 

which provides for access to, copying and verification of 

certain records.

3. Section 519 of the FD&C Act [21 U.S.C. 360i] requires 

manufacturers, importers, or distributors of devices 

intended for human use to maintain such records, and 

provide information as the Secretary may by Regulation 

reasonably require.

4. Section 520(g) of the FD&C Act [21 U.S.C. 360j (g)] 

covers the establishment of exemptions for devices for 

investigational use and the records which must be 

maintained and open for inspection.

QS/GMP requirements for complaint files are found in 21 

CFR 820.198. GMP requirements for complaint files first 

became effective on December 18, 1978. The Quality 

System Regulation, which went into effect on June 1, 1997, 

added to and modified the requirements for complaint 

handling. The regulation contains a provision that records 

maintained in compliance with the QS/GMP must be 

available for review and copying by FDA (21 CFR 820.180).

Complaint files are QS/GMP required records; therefore, 

the manufacturer must make all complaints received on or 

after December 18, 1978 and the records of their 

investigation available for FDA review and copying. EIRs 

should contain enough information to allow crossreferencing between complaints and MDRs.

21 CFR Part 803 requires medical device manufacturers to 

report deaths, serious illnesses, and serious injuries to FDA 

for which a device has or may have caused or contributed, 

and manufacturers must also report certain device 

malfunctions. The MDR reportable events must be 

maintained in a separate portion of the complaint files or 

otherwise clearly identified. These complaints must be 

investigated to determine whether the device failed to meet 

specifications; whether the device was being used for 
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treatment or diagnosis; and the relationship, if any, of the 

device to the reported incident or adverse event.

When a firm determines complaint handling will be 

conducted at a place other than the manufacturing site, 

copies of the record of investigation of complaints must be 

reasonably accessible at the actual manufacturing site.

5.6.3 - STERILE DEVICES

Inspections of sterile device manufacturers are conducted 

per Compliance Program Guidance Manual 7382.845, as a 

production process under the Production and Process

Control Subsystem. See the Guide to Inspections of Quality 

Systems for further guidance.

5.6.4 - LABELING

Specific labeling requirements for in vitro diagnostics (IVDs) 

are contained in 21 CFR 809.10. 

Part 809.10(a) contains explicit labeling requirements for 

the individual IVD containers, and for the outer package 

labeling and/or kit labeling. Part 809.10(b) contains special 

labeling requirements for the product insert, which must be 

included with all IVD products. These two sections also 

contain the requirements for: lot numbers, allowing 

traceability to components (for reagents) or subassemblies 

(for IVD instruments); stability studies for all forms of the 

product; an expiration date, or other indication to assure the 

product meets appropriate standards; and, the 

requirements for establishing accuracy, precision, 

specificity and sensitivity (as applicable).

Part 809.10(c) lists the labeling statements required for 

IVDs which are being sold for investigational and research 

use. Determine whether the firm is limiting the sale of IVDs, 

labeled as such, to investigators or researchers. Document 

any questionable products and submit to CDRH

OHT7:Office of In Vitro Diagnostics for review.

Warning and caution statements recommended for certain 

devices, along with certain restrictions for use, are 

described in 21 CFR 801. This same section also contains 

the general labeling regulations, which apply to all medical 

devices.

5.6.5 - GOVERNMENT-WIDE QUALITY 

ASSURANCE PROGRAM (GWQAP)

Inspections under the GWQAP are conducted upon request 

by Office of Enforcement and Import Operations (OEIO), 

Division of Compliance Systems (DCS). Each assignment 

is specific and may involve more than a single compliance 

program. Specific questions arising during or as a result of 

these inspections should be directed to OEIO/DCS. 

5.6.6 - CONTRACT FACILITIES

Device manufacturers may employ the services of outside 

laboratories, sterilization facilities, or other manufacturers 

(i.e., injection molders, packagers, etc.). The finished 

device manufacturer is responsible for assuring these 

contractors comply with the QS/GMP and that the product 

or service provided is adequate. These contractors are 

subject to FDA inspection and some are subject to the 

QS/GMP regulation. This “...includes but is not limited to 

those who perform the functions of contract sterilization, 

installation, relabeling, remanufacturing, repacking, or 

specification development, and initial distributors of foreign 

entities performing these functions,” per 21 CFR 820.3(o).

Whether under contract or not if a firm manufactures a 

finished device by the definition found in 21 CFR 820.3(l) 

“Finished device” means any device or accessory to any 

device that is suitable for use or capable of functioning, 

whether or not it is packaged, labeled, or sterilized they are 

subject to QS/GMP. NOTE: if the product manufactured by 

the contractor also meets the definition of a component and

a finished device, the contractor is subject to the QS/GMP 

regulation.

Determine how a manufacturer evaluates and selects 

potential contractors for their ability to meet the 

manufacturer's requirements, as required by 820.50, 

Purchasing Controls. Conducting audits can be an effective 

method for assessment. However, not all contractors allow 

audits. Audits may not be feasible in some instances. In 

other instances, the activity the contractor is conducting 

may not have a significant impact on the device safety or 

function; therefore, expending the resources necessary to 

audit the contractor may not be warranted.

Evaluations may be accomplished by other means such as 

requesting that the potential contractor fill out a 

questionnaire about their quality system, asking other 

customers of the contractor about their experiences with 

the firm, or basing assessments on past performance. 

Evaluations must be documented. The extent to which a 

manufacturer has evaluated a contractor, as well as the 

results of the evaluation, should govern the degree of 

oversight exercised over products and services supplied by 

the contractor.

5.6.7 - SMALL MANUFACTURERS

When inspecting one-person or very small manufacturers 

for compliance with the QS/GMP master record and written 

procedure requirements, the investigator should realize 

that detailed written assembly, process, and other 

instructional procedures required for larger firms may not 

be needed. In a small firm, division of work is at a minimum, 

with one person often assembling and testing the finished 

device. In many cases, blueprints or engineering drawings 

could be adequate procedures. The QS regulation requires 

that certain activities be defined, documented and 

implemented. The regulation does not require separate 

procedures for each requirement and often several 

requirements can be met with a single procedure. The 

complexity of the procedures should be proportional to the 

complexity of the manufacturer's quality system, the 

complexity of the organizational structure and the 

complexity/risk of the finished device being produced. In 

assessing the need for detailed or lengthy written 
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procedures, the investigator should make judgments based 

on training and experience of the individuals doing the work 

and the complexity of the manufacturing process. However, 

this does not mean small manufacturers have any less 

responsibility for complying with the QS regulation or 

assuring safe and effective devices are produced.

5.6.8 - BANNED DEVICES

Section 516 of the FD&C Act [21 U.S.C. 360f] provides a 

device for human use may be banned by regulation (21 

CFR 895) if it presents substantial deception or an 

unreasonable and substantial risk of illness or injury. 

Investigators should become familiar with this regulation. 

When you determine, during an inspection or investigation, 

that banned devices are being distributed, the distribution, 

manufacture, etc., should be documented as for any other 

violative product.

5.6.9 – REPORTS OF CORRECTIONS AND 

REMOVALS

Manufacturers, importers, and distributors of medical 

devices are to promptly report to the FDA any corrections 

or removals of a device undertaken to reduce a risk to 

health posed by the device or to remedy a violation of the 

FD&C Act caused by the device which may present a risk 

to health as provisioned by the Safe Medical Devices Act of 

1990 and 21 CFR Part 806. Refer to IOM Ch. 7 – RECALL 

ACTIVITIES and 7.2.3 MEDICAL DEVICE RECALLS for 

more information. 

5.6.10 – TRACKED MEDICAL DEVICES 

A “tracked medical device” is a device regulated by CDRH 

and for which the firm has received “tracking orders”. CDRH 

has a dedicated mailbox to manage inquiries about tracked 

devices and the related regulation at 

TrackedDevicesMailbox@FDA.HHS.GOV. 

5.6.11 - DEVICE INSPECTION REPORTS

See IOM 1.1, English language requirement. You should 

write your EIR following the guidance in IOM 5.11.4, 

5.11.4.1, 5.11.4.2, 5.11.4.3. Section headings can be 

added to address the needs of other Compliance Program 

Guidance Manuals such as 7383.001 for pre-market and 

post-market PMA inspections. Include in your report the 

systems, processes, products, and product classification 

covered during the current inspection.

5.6.12 – Medical Device and Electronic 

Radiation Product Controls (EPRC) 

5.6.12.1 – Electronic Product Radiation 

Controls (EPRC) Inspections

The Radiation Control provisions of the Federal Food Drug 

and Cosmetic Act are located in sections 531 through 542 

(See IOM 2.2.3). These authorities apply to any 

manufactured or assembled product (or component, part, 

or accessory of such product) which when in operation (i) 

contains or acts as part of an electronic circuit and (ii) emits 

(or in the absence of effective shielding or other controls 

would emit) electronic product radiation. Regulations 

promulgated to implement the requirements in this portion 

of the act are contained in 21 CFR 1000 through 1050. 

These sections of the Act and regulation are referred to as 

the Electronic Product Radiation Control (EPRC) 

provisions, and the products subject to these requirements 

referred to as EPRC products. 

All EPRC manufacturers must comply with applicable 

requirements in 21 CFR 1000, 1002, 1003, 1004 and 1005. 

If a mandatory radiation safety performance standard 

applies to a manufacturer’s product, then the manufacturer 

must also comply with 21 CFR 1010 and the product must 

comply with the requirements of the specific standard found 

in 21 CFR 1020 – 1050.

EPRC products may be either medical (that is, they also 

meet the definition of a medical device under the Act) or 

non-medical. Examples are provided below:

• Medical: diagnostic x-ray or ultrasound imaging 

devices, microwave or ultrasound diathermy 

devices, laser coagulators, x-ray or electron 

accelerators, sunlamps, ultraviolet dental curing 

devices

• Non-medical: microwave ovens, televisions 

receivers and monitors (video displays), 

entertainment lasers, industrial x-ray systems, 

laser CD players.

5.6.12.1.1 – Inspection Authority for ERC 

Products

See IOM Section 5.1.1.10 for specific information on the 

authority to inspect facilities subject to EPRC requirements. 

As EPRC inspections have authorities separate from 

section 704 of the FD&C Act, if a refusal to permit the 

planned is encountered, discuss the situation with your 

supervisor on how best to proceed depending on the type 

of assignment and the firm’s operations.

Records required by the Radiation Control provisions of the 

Act must be maintained for five years. 21 CFR 1002(b) 

requires that upon reasonable notice, manufacturers shall 

permit inspection of appropriate books, records, papers, 

and documents as are relevant to determining whether the 

manufacturer has acted or is acting in compliance with 

Federal standards. Firms may retain records in electronic 

or photocopy form, provided the copies are true and 

accurate reproductions.

5.6.12.1.2 – Pre-inspectional Activities for 

EPRC Inspections

Prior to inspecting a facility manufacturing an EPRC 

product, it is important to determine whether the firm 

additionally manufactures medical devices, or if the product 

of interest also appears to be a medical device (e.g. 

medical x-ray, fluoroscopy, medical laser). If the firm 
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manufactures medical devices, or the product of interest is 

also a medical device, it is recommended a joint 

EPRC/Medical Device inspection be planned. If Medical 

Device coverage is anticipated during the inspection, see 

additionally the pre-inspectional activities outlined within 

IOM 5.6.2.1. Guidance for preparing for EPRC inspections 

is provided based on the product type in the Compliance 

Programs. listed in IOM 5.6.12.1.3.

Certain required submissions by these firms, such as 

Annual Reports and Accidental Radiation Occurrences, 

may be obtained from queries in the Center Tracking 

System (CTS). 

EPRC inspections, whether or not in conjunction with a 

medical device inspection, should only be conducted by 

individuals with appropriate training and experience. Those 

not trained to conduct EPRC inspections may participate as 

part of a team with an EPRC trained investigator. Notify 

your supervisor prior to pre-announcement if during 

preparations you have questions regarding the training 

required to complete the operation. 

Radiation-emitting devices and substances present a 

unique hazard and risk potential. Every effort should be 

taken to prevent any undue exposure or contamination. 

Monitoring devices must be used whenever radiation 

exposure is possible; for these types of inspections that 

may include one or more dosimeter. To be added to the 

dosimetry program and obtain appropriate monitoring 

equipment in advance of an inspection, see SOP -000927 

Radiation Dosimetry Program. 

If the inspection will be covering medical device 

requirements, pre-announcement may be required 

depending on the nature of the assignment (see IOM 

5.2.1.1.2 for which inspections require pre-announcement). 

If only EPRC coverage is planned, pre-announcement is 

not required, but is generally recommended. Preannouncement may facilitate the inspection, ensuring 

necessary personnel and records are there, as well as 

ensure that appropriate safety protocols are known to 

prevent unintended exposure during the operation. Consult 

your supervisor if you believe pre-announcement is not 

warranted for an EPRC inspection.

5.6.12.1.3 – Inspection of EPRC Facilities

Inspections of facilities manufacturing EPRC products may 

vary depending on the product type and the nature of the 

assignment. Guidance for coverage of these operations is 

provided in the applicable CPGM below:

• Laser Products (Medical and Non-Medical) – 

7386.001 Inspection and Field Testing of 

Radiation-Emitting Electronic Products

• Sunlamp – 7386.001 Inspection and Field Testing 

of Radiation-Emitting Electronic Products

• Medical X-Ray Products – 7386.003a Inspection 

of Domestic and Foreign Manufacturers of 

Diagnostic X-ray Equipment

• Non-Medical X-Ray Products - 7386.001 

Inspection and Field Testing of Radiation-Emitting 

Electronic Products

If during the inspection of a medical device manufacturer, 

you determine that one or more of their devices emits 

radiation and is subject to EPRC, consult your supervisor 

on whether expansion of the inspection to include coverage 

of those requirements is appropriate.

Significant issues developed during coverage of EPRC 

requirements should be documented on the Form FDA 483, 

Inspectional Observations. If both EPRC and medical 

device observations are being issued on a Form FDA 483, 

Inspectional Observations, they should be grouped

separately on the form using text subheadings

SUBCHAPTER 5.7 - BIOLOGICS

5.7.1 - DEFINITION

A "biological product" means a virus, therapeutic serum, 

toxin, antitoxin, vaccine, blood, blood component or 

derivative, allergenic product, protein (except any 

chemically synthesized polypeptide) or analogous product, 

or arsphenamine or derivative of arsphenamine (or any 

other trivalent organic arsenic compound), applicable to the 

prevention, treatment, or cure of a disease or condition of 

human beings (Public Health Service Act Sec. 351(i)). 

Additional interpretation of the statutory language is found 

in 21 CFR 600.3. Biological products also meet the 

definition of either a drug or device under Sections 201(g) 

and (h) of the Federal Food, Drug, and Cosmetic Act 

(FD&C Act).

Veterinary biologicals are subject to the animal Virus, 

Serum, and Toxin Act which is enforced by USDA (21 

U.S.C. 151-158).

5.7.2 - BIOLOGICS INSPECTIONS

The periodic CGMP inspections and compliance operations 

of plasma fractionated products, allergenic products, 

vaccines, gene and cell therapy products, and biological in 

vitro diagnostic devices are led by investigators from ORA’s 

Office of Biological Products Operations (OBPO). OBPO 

investigators also lead inspections of unlicensed CBERregulated medical devices (e.g., blood establishment 

software). See IOM 2.2 for a discussion of statutory 

authority. CBER maintains the lead for pre-licensing and 

most pre-approval inspections of biological products, while 

ORA customarily leads PMA/510(k) inspections.

5.7.2.1 - Authority

Biological products are regulated under the authority of 

Section 351 of the Public Health Service Act and under the 

Food, Drug, and Cosmetic Act, as drugs or devices, with 

the exception of certain human cells, tissues, and cellular 

and tissue-based products (HCT/Ps) regulated solely under 

Section 361 of the Public Health Service Act (see 21 CFR 
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1271.10). Blood and blood products for transfusion are 

prescription drugs under the FD&C Act. Under the FD&C 

Act, source plasma and recovered plasma may have the 

legal identity of either a drug or device depending on its 

intended use. Section 351(a) of the PHS Act provides for 

licensure of biological products and inspection of the 

products covered is per 351(d). Most biological drugs are 

licensed. The investigational new drug application 

regulations (21 CFR 312) also apply to biological products 

subject to the licensing provisions of the PHS Act. However, 

investigations of blood grouping serum, reagent red blood 

cells, and anti-human globulin in-vitro diagnostic products 

may be exempted (21 CFR 312.2(b)).

5.7.2.1.1 - BLOOD AND SOURCE PLASMA 

INSPECTIONS

For blood bank and source plasma establishment 

inspections (CP 7342.001 & 7342.002) use the CGMPs for 

Blood and Blood Components (21 CFR 606) as well as the 

general requirements for biological products (21 CFR Part 

600), the general biological product standards (21 CFR Part 

610), and the additional standards for human blood and 

blood products (21 CFR Part 640.) The drug GMPs (21 

CFR 210/211) also apply to biological drugs. In the event it 

is impossible to comply with both sets of regulations, the 

regulation specifically applicable to the product applies. 

This would generally be Parts 606 and 640 of the 

regulations in the case of blood bank and source plasma 

establishments.

5.7.2.1.2 – HUMAN TISSUE INSPECTIONS

21 CFR Part 1271 contains six subparts:

1. Subpart A of part 1271 – general provisions

2. Subpart B of part 1271 - registration

3. Subpart C of part 1271 - screening and testing of donors 

to determine eligibility

4. Subpart D of part 1271 - provisions on CGTP

5. Subpart E of part 1271 - certain labeling and reporting 

requirements

6. Subpart F of part 1271 - inspection and enforcement 

provisions.

The subparts apply as follows:

Subparts A through D apply to all HCT/Ps, i.e., to those 

HCT/Ps described in Sec. 1271.10 and regulated solely 

under section 361 of the PHS Act, and to those regulated 

as drugs, devices, and/or biological products. Subparts E 

and F, which pertain to labeling, reporting, inspection, and

enforcement, apply only to those HCT/Ps described in Sec. 

1271.10 and regulated solely under section 361 of the 

PHS Act. However, with the exception of two provisions 

(Sec. 1271.150(c) and 1271.155) subparts D and E are not 

being implemented for reproductive HCT/Ps described in 

21 CFR 1271.10 and regulated solely under section 361 

of the PHS Act. 

HCT/Ps subject to the provisions of 21 CFR Part 1271

include, but are not limited to, bone, ligaments, skin, dura 

mater, heart valve, cornea, hematopoietic stem/progenitor 

cells derived from peripheral and cord blood, manipulated 

autologous chondrocytes, epithelial cells on a synthetic 

matrix, and semen or other reproductive tissue.

For HCT/P inspections, use the CP 7341.002, “Inspections 

of Human Cells, Tissues, and Cellular and Tissue-Based 

Products.”

5.7.2.2 – Donor Confidentiality

Blood bank, source plasma, and human tissue 

establishments are sensitive to maintaining confidentiality 

of donor names. The mere reluctance to provide records is 

not a refusal. However, FDA has the authority under both 

the PHS and the FD&C Acts to make inspections and 21 

CFR 600.22(g) and 1271.400(d) provides for copying 

records during an establishment inspection. For 

prescription drugs, section 704 of the FD&C Act specifically 

identifies records, files, papers, processes, controls, and 

facilities as being subject to inspection.

If you encounter problems accessing records, explain 

FDA's authority to copy these records. IOM 5.2.5 should be 

followed if a refusal is encountered. When donor names or 

other identifiers are necessary, they may be copied, but the 

information must be protected from inappropriate release. 

See IOM 5.3.8.6.

5.7.2.3 – Inspectional Objectives

The inspectional objective for biological products is to 

assure the products are safe, effective, and contain the 

quality and purity they purport to possess and are properly 

labeled. The inspectional objective for HCT/Ps is to assure 

that HCT/Ps are recovered, processed, stored, labeled, 

packaged and distributed, and the donors are screened and 

tested, in a way that prevents the introduction, 

transmission, or spread of communicable diseases. 

Facilities will be inspected for conformance with:

1. Provisions of the PHS Act and FD&C Act,

2. Applicable regulations in: 

• 21 CFR 210-211

• 21 CFR 600-680, and

• 21 CFR 820

3. HCT/P regulations in 21 CFR 1270 and 1271. 

4. FDA Policies, which include guidance to the industry, 

and the Compliance Policy Guides Chapter 2. 

5.7.2.4 - Preparation

Review the program division files of the facility to be 

inspected and familiarize yourself with its operation and 

compliance history. Review:

1. Appropriate Compliance Programs and related 

Compliance Policy Guides (CPG), Chapter 2. 

NOTE: Federal Cooperative Agreements Manual; MOU 

with the Department of Defense, and MOU with the 

Centers for Medicare and Medicaid Services (CMS) on 

transfusion services;

2. Correspondence from the firm depicting any changes 

since the last inspection;
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3. Firm's registration and product listing information;

4. Biological Product Deviation Reports, Adverse Reaction 

Reports, complaints, and recalls;

Through guidance documents, CBER sets forth its 

inspection policy and regulatory approach. A list of these 

documents is attached to the current Compliance Program 

Guidance Manuals (CP) available on the CBER internet site 

at (CBER CP Website).

The OSHA regulation 29 CFR 1910.1030 dated December 

6, 1991, was intended to protect health care workers from 

blood borne pathogens, including those involved in the 

collection and processing of blood products. The regulation 

defines expectations for the use of gloves, hand washing 

facilities, decontamination of work areas, waste containers, 

labeling and training of employees and exemptions for 

volunteer blood donor centers. FDA Investigators should 

adhere to these safety guidelines during inspections or 

related activities in establishments that process biologically 

hazardous materials.

Become familiar with the OSHA regulations and their 

applicability to 21 CFR 606.40(d)(1) and (2), which require 

the safe and sanitary disposal for trash, items used in the 

collection and processing of blood and for blood products 

not suitable for use. Consult your program division biologics 

monitor for copies of the above references. Additional 

copies may be obtained from OO, OMPTO, Division of 

Medical Products and Tobacco Program Operations or see 

CBER's web site. 

5.7.2.5 - Inspectional Approach

Use the Compliance Program (CP) for inspectional 

instructions. Particular attention should be given to 

biological products deviation reports indicative of 

problematic areas or processes, adverse reactions, 

transfusion or donation associated fatalities and hepatitis 

and HIV lookback procedures. The follow-up investigations 

to such reports should also be covered.

Complaints, in particular those involving criminal activity, 

must be promptly investigated and coordinated with other 

agency components as needed.

For blood banks and source plasma establishments, refer 

to CP 7342.001 and 7342.002 for a discussion of the 

systems approach to inspection. The CP incorporates a 

systems-based approach to conducting an inspection and 

identifies five (5) systems in a blood bank and source 

plasma establishment operation for inspection. Each 

system may not be in a particular establishment operation; 

therefore, the inspection should focus on the systems 

present. The CP directs an in-depth audit of the critical 

areas in each system. A multi-layered system of safeguards 

has been built into the blood collection, manufacturing and 

distribution system to assure a safe blood supply.

For HCT/P establishments, refer to CP 7341.002. 

For Biological Drug Products, refer to CP 7345.848. 

For Licensed In-vitro Diagnostic Devices Regulated by 

CBER , refer to CP 7342.008. 

If Investigators encounter products not specifically 

referenced in the regulations, they should contact 

CBER/OCBQ/ Division of Inspections and Surveillance for 

guidance.

5.7.2.5.1 Access of Electronic Databases and 

Queries

Overseeing the firm’s personnel while they access their 

system is not always practical. For these reasons, if all the 

following criteria are met, OBPO investigators are permitted 

to access a firm’s records using a read-only account, 

dummy terminal, or comparable mechanism when 

necessary: 

• Responsible management at the firm is agreeable to 

allowing read-only access to electronic systems and/or 

databases; 

• Access to electronic systems/databases is read only 

and will not permit you to change or alter data or 

programming in any manner; 

• The firm has a representative that will be available to 

initially describe and review the layout of their records, 

and make themselves available throughout the 

inspection as additional information or copies of 

records are needed; and 

• You document this read-only access in your regulatory 

notes, establishment inspection report, or

investigational memorandum accordingly.

5.7.2.6 - Regulations, Guidelines, 

Recommendations

Guidance documents for industry are made available to the 

public in accordance with good guidance practice 

regulations at 21 CFR 10.115. The contents of most of

these documents are incorporated into the establishment's 

SOPs and/or license applications or supplements. 

Deviations from guidance documents must not be 

referenced on an FDA 483. However, since these 

documents are often related to specific GMP requirements, 

in most cases deviations can be referenced back to the 

GMP. If a deviation is observed during an inspection and 

the investigator relates it to the regulations or law, then the 

item may be reported on the FDA 483. During the 

discussion with management, the relationship of the 

deviation to the regulation or law, or accepted standard of 

industry, should be clearly explained.

If an establishment indicates it is not aware of any of these 

documents, provide them the guidance document(s) or 

direct them where to find these documents on 

www.fda.gov. Provide the firm with the email address for 
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industry in order to obtain additional information from CBER 

at industry.biologics@fda.hhs.gov.

If a firm claims approval for an alternative procedure, verify 

by reviewing the firm's written approval letter. Approved 

alternative procedures may be verified by contacting 

CBER/Division of Blood Applications or the appropriate 

CBER product office.

5.7.2.7 - Technical Assistance

The services of National Experts and Program Experts in 

ORA/OMPTO are available for telephone or on-site 

consultation and assistance in problem areas (see FMD142). 

5.7.2.8 Biologics Establishment Inspection 

Reports

See IOM 1.1, English language requirement. You should 

write your EIR following the guidance in IOM 5.11.4, 

5.11.4.1, 5.11.4.2, 5.11.4.3. Section headings can be 

added to address the needs of specific Compliance 

Program referenced in conducting the inspection. Where 

applicable and per the CP, the report should state the levels 

of the inspection and systems that were covered. The 

reasoning for the level and systems covered must be 

reported, as directed in the CPs. The report should also 

include a summary, the FDA 482, the FDA 483, if issued, 

and the required eNSpect record in OSAR.

The scope of the reporting should reflect requirements and 

regulations for each area, the firm’s state of compliance, 

previous inspectional report(s) and information, complexity 

of operations, and other aspects that may affect the 

reporting that will be necessary.

For directed inspections with a narrow focus, such as 

complaint follow-up or center-directed assignments include 

information to appropriately cover the assignment. Follow 

specific instructions included in any associated assignment 

memorandum.

5.7.3 - REGISTRATION, LISTING AND 

LICENSING.

5.7.3.1 - Registration and Listing 

See IOM 2.9.3.1

5.7.3.1.1 – TRANSFUSION SERVICES 

Most transfusion services are exempt from registration 

under 21 CFR 607. This includes facilities that are certified 

under the Clinical Laboratory Improvement Amendments of 

1988 (42 U.S.C. 263a) and 42 CFR Part 493 to perform the 

FDA-required tests on blood or has met equivalent 

requirements as determined by the Centers for Medicare 

and Medicaid Services, and are engaged in the 

compatibility testing and transfusion of blood and blood 

components, but which neither routinely collect nor process 

blood and blood components. Such facilities include 

establishments:

1. Collecting, processing and shipping blood and blood 

components under documented emergency situations,

2. Performing therapeutic phlebotomy and therapeutic 

plasma exchange after which the product is discarded,

3. Preparing recovered human plasma and red blood cells,

4. Pooling products/platelets for in-house transfusion,

5. Thawing frozen plasma or cryoprecipitate for 

transfusion.

All VA Blood Banks and Hospital Transfusion Services 

must register with FDA since they are not inspected by 

CMS.

5.7.3.1.2 - HCT/PS

Establishments manufacturing HCT/Ps (human cells, 

tissues, or cellular or tissue-based products) as defined in 

21 CFR 1271.3(d) must register and list using form FDA 

3356. Examples of HCT/Ps include, but are not limited to, 

bone, ligament, skin, cornea, hematopoietic stem cells 

derived from peripheral and cord blood, manipulated 

autologous chondrocytes, and semen or other reproductive 

tissue. 

Establishments that only manufacture investigational 

HCT/Ps under an IND or IDE are not required to register

and list until the HCT/P has been licensed, approved, or 

cleared by FDA. Establishments manufacturing HCT/Ps 

regulated as drugs and/or biological products must register 

and list with FDA pursuant to 21 CFR 207. Establishments 

manufacturing HCT/Ps regulated as medical devices must 

register and list with FDA pursuant to 21 CFR 807.

5.7.3.1.3 - LABORATORIES

Laboratories performing infectious disease testing of 

donors of blood or blood components or HCT/P are an FDA 

obligation and required to register. Clinical laboratories 

were previously exempted from registration by 21 CFR 

607.65(g), but FDA revoked this regulation. Your 

inspections should focus on activities relevant to blood 

product and HCT/P testing operations.

5.7.3.1.4 - MILITARY BLOOD BANKS

Inspection of military blood banks is an ORA responsibility. 

These facilities are required to meet the same standards as 

other blood banks although military emergencies may 

require deviations from the standards. A separate license 

is held by each branch of the service; although each 

individual establishment may be licensed or unlicensed, all 

are required to register. Program divisions should notify the 

appropriate military liaisons 30 days before inspection of a 

military facility. For additional information on inspection of 

government establishments, see Compliance Program 

Guidance Manual 7342.001, the Federal Cooperative 

Agreements Manual, and the MOU with Department of 

Defense Regarding Licensure of Military Blood Banks.
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Foreign notification of Military Blood Banks is done by the 

Trip Planner in preparation of the international trip.

Field Management Directive 92, Agency Establishment 

Registration and Control Procedures, details the 

registration process within the agency. 

Ensure the firm's current registration forms reflect actual 

operations.

5.7.3.2 – MOUs

Under the 1983 Memorandum of Understanding (MOU) 

between the FDA and the Centers for Medicare and 

Medicaid Services (CMS, formerly Health Care Financing 

Administration - HCFA), CMS agreed to survey these 

facilities that engage in minimal manufacturing in order to 

minimize duplication of effort and reduce the burden on the 

affected facilities while continuing to protect transfusion 

recipients. However, no transfer of statutory functions or 

authority is made under the MOU and the FDA retains legal 

authority to inspect these unregistered transfusion services 

whenever warranted. When appropriate, program divisions 

should conduct inspections jointly with the CMS regional 

liaison. If you determine during a routine inspection an 

establishment is a CMS obligation under the MOU, you 

should terminate the inspection and report as such. See 

Federal Cooperative Agreements Manual - FDA/HCFA 

MOU. 

5.7.3.3 - Biologics License

See IOM 2.9.3.2. A biologics license application (BLA) 

shall be approved only after inspection of the 

establishment(s) listed in the application and upon a 

determination that the establishment complies with the 

standards established in the BLA and the requirements 

prescribed in applicable regulations (21 CFR 601.20(d)). 

CBER maintains the lead for pre-license (PLI) and preapproval (PAI) inspections of biological products. These 

inspections are part of the review of a BLA or BLA 

supplement. CBER identifies the scope of the inspection 

and invites ORA to participate in or may request ORA lead 

the PLI or PAI.

Copies of CBER's PLI and PAI inspection

reports are forwarded to the Program Divisions and are

stored in the firm’s eCMS file. These inspection reports can 

also be located in eNSpect and OSAR.

5.7.3.4 - Approval of Biological Devices

There must be a pre-approval inspection (PAI) of the 

establishment for compliance with the QS/GMP regulation 

and the firm's PMA. For licensed devices, CBER conducts 

the pre-license inspection (PLI). Devices used in the 

collection and testing of blood for transfusion are 

approved/cleared through the PMA/510(k) authorities. ORA 

Investigators customarily inspect the CBER regulated 

devices, which are subject to PMA/510(k) applications.

5.7.4 - TESTING LABORATORIES

Blood bank, source plasma, and HCT/P establishments 

may use outside testing laboratories to perform required 

testing.

Laboratories conducting testing for licensed blood banks 

are usually licensed. CBER may approve the use of a nonlicensed laboratory to do required testing, provided the lab 

is capable of performing the tests and the lab registers with 

CBER prior to CBER approving the licensing arrangement.

Laboratories performing required testing for source plasma 

manufacturers must either be:

1. licensed or

1. certified to perform such testing on human specimens 

under the Clinical Laboratory Improvement 

Amendments of 1988 (42 U.S.C. 263a) and 42 CFR part 

493, or has met equivalent requirements as determined 

by CMS.

Instructions for inspecting testing laboratories are included 

in the appropriate CP. Coordinate the inspection of nonregistered laboratories with CMS regional office contacts. If 

a testing laboratory is located outside of the program 

division, request an inspection by the appropriate program 

division office, where appropriate.

See updated information on: Donor Screening Assays for 

Infectious Agents and HIV Diagnostic Assays; and HCT/P 

donors for Relevant Communicable Disease Agents at 

FDA.gov.

5.7.5 - BROKERS

Blood establishments may use brokers to locate buyers for 

products such as recovered plasma or expired red blood 

cells. These articles are used for further manufacture into 

products such as clinical chemistry controls and in-vitro 

diagnostic products not subject to licensure. Fractionators 

also use brokers to locate suppliers of plasma under the 

short supply provisions (21 CFR 601.22). During 

inspections, determine if the facility is selling products to 

any brokers. If brokers are used, determine if the brokered 

products are shipped to a facility operated by the broker or 

directly to the consignee.

Brokers who take physical possession of blood products 

and engage in activities considered manufacturing or 

labeling are required to register and are included in the OEI 

for routine inspection under the blood bank compliance 

program. Brokers who only arrange sales of or store blood 

and blood components, but do not engage in manufacturing 

activities are not required to register.

SUBCHAPTER 5.8 - TOBACCO PRODUCTS

5.8.1 - DEFINITIONS

The term "tobacco product" is defined in FD&C Act 

Section 201(rr) and means any product made or derived 

from tobacco, or containing nicotine from any source, that 
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is intended for human consumption, including any 

component part, or accessory of a tobacco product 

(except for raw materials other than tobacco used in 

manufacturing a component, part, or accessory of a 

tobacco product.) The term "tobacco product" does not 

mean an article that is a drug under section 201(g)(1) of 

the FD&C Act, a device under section 201(h) of the FD&C 

Act, or a combination product described in section 503(g) 

of the FD&C Act. The term ‘‘tobacco product’’ does not 

mean an article that is a food under section 201(f) of the 

FD&C Act, if such article contains no nicotine, or no more 

than trace amounts of naturally occurring nicotine. 

The definition of certain tobacco products can be found in 

the FD&C Act under section 900.

5.8.2 – TOBACCO INSPECTIONS

See IOM 2.2 for discussion of statutory authority

Inspections involving tobacco product(s) at manufacturing 

facilities are led by ORA’s Tobacco Operations Staff 

(TOS) within the Office of Medical Products and Tobacco 

Operations and are conducted pursuant to assignments 

issued by CTP. These assignments are issued to conduct 

inspections of entities engaged in the manufacture, 

preparation, compounding, or processing of tobacco 

products. Inspections may also be conducted to support 

the pre-market review process. Assignments may also be 

issued to conduct investigations and sample collections. 

CTP Subject Matter Experts may accompany ORA’s 

Tobacco Operations Staff during inspections. Additional 

guidance on deemed tobacco products can be found on 

CTP's Deeming webpage. 

https://www.fda.gov/tobacco-products/rules-regulationsand-guidance/fdas-deeming-regulations-e-cigarettescigars-and-all-other-tobacco-products.

5.8.3 - RETAIL COMPLIANCE CHECK 

INSPECTION CONTRACTS

FDA issues contracts to assist with compliance check 

inspections of tobacco retail establishments to help 

determine a retailer's compliance with federal laws and 

regulations, including the Federal Food, Drug, and 

Cosmetic Act, as amended by the Tobacco Control Act, and 

associated regulations. FDA has a goal of establishing a 

contract, where feasible, with every U.S. State and 

Territory, but some States and Territories, for a variety of 

reasons, have been unable to do so. Therefore, FDA has 

awarded contracts to third- party entities that are able to 

hire commissionable inspectors to conduct compliance 

check inspections of tobacco retailers in those states and 

territories where FDA was unable to contract with a 

government agency. FDA has further expanded this 

program by awarding retail inspection contracts to 

American Indian and Alaska Native Tribes to conduct retail 

inspections within their jurisdictions. In addition, FDA may 

also conduct inspections using FDA personnel.

5.8.4 - GUIDANCE, COMPLIANCE & 

REGULATORY INFORMATION

The Center for Tobacco Products website contains 

resources for legal, regulatory, and policy issues related to 

tobacco products and information for small business 

assistance (SmallBiz.Tobacco@fda.hhs.gov) 

SUBCHAPTER 5.9 - VETERINARY MEDICINE

5.9.1 - CVM WEBSITE

The Center for Veterinary Medicine website contains; a 

listing of current and planned Guidance Documents; and 

on-line access to the Animal Drug@fda database listing 

new animal drug approvals. There is a "search" feature 

allowing you to search for documents containing various 

words or phrases. The website also contains organizational 

information for the Center and an explanation of the various 

laws and regulations which the Center enforces. 

Information on the website can provide guidance for 

inspectional efforts related to CVM obligations. 

5.9.2 - VETERINARY DRUG ACTIVITIES

CVM is responsible for work planning inspections of 

therapeutic and production drugs, and Active 

Pharmaceutical Ingredients (APIs). Therapeutic drugs are 

used in the diagnosis, cure, mitigation, treatment or 

prevention of disease. Production drugs are used for 

economic enhancement of animal productivity. Examples 

include: growth promotion, feed efficiency and increased 

milk production.

Pre-approval inspections are conducted pursuant to 

pending NADA or ANADA applications.

Post approval inspections of veterinary drugs are 

conducted to determine compliance with the Current Good 

Manufacturing Practices (CGMPs) for Finished 

Pharmaceuticals under 21 CFR Part 211. These cGMPs 

apply to both human and veterinary drugs. Information on 

veterinary drugs approved can be found in the "Green 

Book" database accessed through CVM's website.

APIs are active pharmaceutical ingredients. Many of the 

APIs used to manufacture dosage form drugs are imported 

from foreign countries. The intended source for an API must 

be indicated in NADA/ANADA submissions for new animal 

drug approvals. Any change in a source for an API would 

require a supplement to the application.

Extra label drug use refers to the regulations in 21 CFR Part 

530 codified as a result of the Animal Medicinal Drug Use 

Clarification Act (AMDUCA) of 1994. These regulations set 

forth the requirements that veterinarians must meet to 

prescribe extra label uses of FDA approved animal and 

human drugs. The regulations describe what is a valid 

veterinary-client-patient relationship as well as what is 
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considered illegal extra label use. 21 CFR Part 530 

addresses issues regarding extra label use in non-food as 

well as food producing animals. 21 CFR 530.41 contains a 

list of drugs that cannot be used in an extra label manner in 

food-producing animals. During an inspection or 

investigation if you encounter any situations on suspected 

illegal extra label use of any FDA approved animal or 

human drugs or those prohibited for extra label use in food 

animals, you should contact CVM's Division of Drug

Compliance (HFV-210).

21 CFR Part 530 also addresses compounding of products 

from approved animal or human drugs by a pharmacist or 

veterinarian. The regulations clearly state compounding is 

not permitted from bulk drugs. This would include APIs. 

CVM has an existing CPG on Compounding of Drugs for 

Use in Animals (CPG 608.400). A copy can be found on 

CVM's website. The Division of Drug Compliance (HFV210) has issued assignments to conduct inspections of 

firms, including internet pharmacies, who may be engaged 

in the practice of manufacturing under the guise of 

pharmacy compounding. You should contact the Division of 

Compliance (HFV-230) at 240-276-9200 to report 

instances of compounding or to seek guidance on 

inspectional issues, or regulatory and enforcement policies.

5.9.3 - MEDICATED FEEDS AND TYPE A 

ARTICLES

Animal feed is defined under section 201(w) of the FD&C 

Act [21 U.S.C. 321 (w)]. CVM is responsible for control of 

medicated and non-medicated animal feeds, Type A 

medicated articles and pet foods.

The regulations for animal food labeling are in 21 CFR Part 

501. The regulations for medicated feed mill licensure are 

in 21 CFR Part 515. The cGMPs for Medicated Feeds are 

in 21 CFR Part 225. The cGMPs for Type A Articles are in 

21 CFR Part 226. 

Inspections are routinely conducted of medicated feed mills 

and manufacturers of Type A Medicated Articles.

If you have questions related to cGMPs and enforcement 

policies and strategies concerning Medicated Feeds and 

Type A Articles you should contact the CVM/Division of 

Food Compliance at 

CVMAnimalFoodPrograms@fda.hhs.gov. 

Guidance on pet food labeling requirements can be found 

on CVM's website.

5.9.4 - BSE ACTIVITIES

CVM is responsible for FDA's industry education and 

regulatory activities involving BSE and animal feed. BSE is 

"Bovine Spongiform Encephalopathy" and is often referred 

to as "mad cow disease." There are two BSE-related feed 

regulations: 21 CFR 589.2000, entitled “Animal Proteins 

Prohibited in Ruminant Feed” which was adopted in 1997, 

addresses the feeding of ruminant animals. A second rule, 

21 CFR 589.2001, entitled “Cattle Materials Prohibited in 

Animal Food or Feed to Prevent the Transmission of Bovine 

Spongiform Encephalopathy” was adopted in 2009. 21 CFR 

589.2001 prohibits the use of certain cattle-origin materials 

in the feed of all animals and is aimed primarily at rendering 

operations. 

CVM has Guidance Documents in place dealing with BSE. 

The guidance documents address renderers, protein 

blenders, feed manufacturers, distributors and on farm 

feeders. The Compliance Program Guidance Manual and 

the inspection checklist are available on the CVM website, 

as are a variety of other BSE information, including a 

database containing a summary of the most recent 

inspection of each firm.

Questions on inspectional assignments and regulatory 

activities in the BSE area should be addressed to the 

CVM/Division of Food Compliance (HFV-236) 

CVMAnimalFoodPrograms@fda.hhs.gov. . 

5.9.4.1 – Biosecurity Procedures for BSE 

Inspections at Poultry Facilities and Farms

Given our recent experiences with highly pathogenic 

animal viruses such as porcine epidemic diarrhea virus 

(PEDV) in 2013 and 2014, and highly pathogenic avian 

influenza (HPAI) in 2015, we expect everyone conducting 

feed inspections on FDA’s behalf to observe routine, 

simple, biosecurity precautions for all of your routine feed 

inspection work going forward. 

In summary: and in addition to FDA’s Biosecurity 

Guidance/procedures: 

1) Follow the biosecurity plan for the facility being visited if 

they have one. 

2) Plan your daily work so you do not carry contamination 

from one location to another. As much as possible, plan to 

work from cleanest to dirtiest on a given day, whether this 

is within a single facility, or across multiple facilities. 

3) Wear clean shoes and clothes and use clean equipment. 

4) Practice good personal hygiene, such as hand-washing 

and bathing. 

5) Change or clean your shoes between inspection sites if 

they get dirty or wear disposable shoe coverings. 

6) Visiting a farm to conduct a feed inspection should not 

require any contact with farm animals in most situations, 

and animal contact should be avoided unless it is absolutely 

necessary. 

7) Be cognizant of recent contact with any livestock or 

poultry, including your own or those belonging to friends, 

families or neighbors, pet birds, and things like hunting, and 

consider it as you plan you work. 

8) As much as possible, avoid going from one farm to 

another on a single day. If you do need to go from one farm 

to another, it may be necessary to change clothes or shoes, 

or even take a shower which is why we are encouraging the 
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planning of work in such a way that contamination is not 

carried from one site to another. 

9) Make an appointment to conduct routine on- farm 

inspections. 

For the most part, the information above is a brief, highlevel summary of Section 5.2.10. “Routine Biosecurity 

Procedures for Visits to Facilities Housing or Transporting 

Domestic or Wild Animals 

CVM asks that all routine assigned work (covered in the 

work-plan or an assignment) involving on –farm feed 

inspections be pre-announced. This will allow the CSO the 

opportunity to ask about biosecurity procedures and help 

make sure someone is present.

5.9.5 - DRUG RESIDUES

The presence of violative drug residues in food from 

slaughtered animals is a human health concern. Drug

residue inspections are performed in response to reports of 

violative drug residue levels found in tissue sampled at 

slaughter by the USDA/Food Safety Inspection Service 

(FSIS).

Drug residues are commonly caused by medicating 

animals prior to marketing and failure to follow the drug’s 

approved label directions. When a new animal drug is 

approved the approval is very specific in how the drug 

should be used, the dosage it should be given, route of 

administration, frequency of use and reason for use. A drug 

manufacturer conducts studies to determine withdrawal 

times and these times must be followed. Established 

tolerances for drug residues of new animal drugs in food 

can be found in 21 CFR Part 556. 

Drug residue investigations are unique in comparison to 

other fieldwork. Although your investigation may begin at 

the USDA slaughter establishment or person named on the 

USDA/FSIS “Violation Notification Letter,” you may inspect 

and/or visit more sites as part of your overall investigation. 

You may have to visit an auction barn, dealer, trucker, 

veterinarian, drug supplier, slaughter facility (USDA firm 

management or State personnel), etc. One or more of these 

establishments may be responsible for the drug residue. 

Thus, each establishment's activities may warrant a 

recommendation for regulatory action such as Warning 

Letter, Injunction, etc. when involvement with residue 

violations is documented. 

Upon receipt of a FACTS assignment from CVM to conduct 

a drug residue follow-up investigation, the program division

may also create additional operations, linked to the original 

CVM assignment, which will include all operations required 

to complete the CVM assignment. This could include 

multiple inspections, sample collections and/or 

investigations. You may not be aware of all the 

establishments you will visit prior to beginning your 

investigation. Appropriate operations should be added to or 

deleted from the program division assignment. 

Each site visit is unique, and each produces its own set of 

unique documents and evidence requiring individual 

reporting by establishment. You should use good judgment 

during case development to assure you document your 

investigation thoroughly. Explain the chain of events and 

evidence, from the initial drug residue report, and how other 

establishments were involved. Collect samples (usually 

DOC samples) as appropriate. Consultation with your 

supervisor and/or compliance branch during these 

operations is essential to assure all evidence necessary to 

develop a quality case is obtained and submitted in an 

appropriate format.

Following completion of all operations, you should prepare 

a Memo of Investigation referencing the FACTS 

assignments for your supervisor’s endorsement to the 

program division Compliance Branch, with a copy to the 

originating CVM office. This Memo will summarize each site 

visit (EI or Investigation), sample(s) collected and relevance 

to the overall CVM assignment. A copy of the memo will be 

routed to each appropriate factory file.

The individual operations will then stand alone and/or may 

be used together to build one or multiple cases.

For example, a site visit to a slaughter facility may obtain 

information on the animal from the USDA inspection 

personnel on site; and obtain verification from management 

the establishment ships in interstate commerce. 

Information obtained at the slaughter facility or other 

establishments may be documented in an affidavit from 

each individual providing salient information. A site visit to

a veterinarian may be important to establish whether the 

drugs which caused the drug residue(s) were prescribed 

and, if so, how they were prescribed. When there is reason 

to believe off-label use or other activities have occurred 

which may warrant a recommendation for regulatory action, 

an establishment inspection should be conducted, and your 

evidence included with your report. Refer to the 

Compliance Program 7371.006, “Illegal Residues in Meat, 

Poultry, Seafood and other Animal Derived Foods” for in 

depth instructions on how to conduct a drug residue 

inspection.

For information on drug residue violations and activities you 

should contact the CVM/Division of Food Compliance 

(HFV-236) CVMAnimalFoodPrograms@fda.hhs.gov. 

5.9.6 - VETERINARY DEVICES

Medical devices for animal/veterinary use are not subject to 

the premarket approval requirements like human medical 

devices. Once an animal use device is marketed the Center 

is concerned with safety and efficacy of the veterinary 

device. CVM often recommends firms use the human 

device GMPs in controlling the manufacturing of animal use 

devices. CVM also suggests labeling be sent in for review 

by the Division of Drug Compliance (HFV-210) 

(ASKOCS@fda.hhs.gov) to avoid misbranding. Regulatory 

questions for veterinary/animal use devices should be 
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directed to the CVM/Division of Drug Compliance (HFV210) (ASKOCS@fda.hhs.gov. 

5.9.7 - ANIMAL GROOMING AIDS

Grooming aids for animals formulated and labeled only to 

cleanse or beautify the animal are not cosmetics within the 

meaning of Section 201(i) and not subject to the Federal 

Food, Drug, and Cosmetic Act. Where animal grooming 

aids are labeled to contain an active drug ingredient or 

otherwise suggest or imply therapeutic benefit, they may be 

considered to be drugs and/or new animal drugs as defined 

by Section 201(v) of the Act (see CPG 653.100). 

Questions on labeling and regulatory concerns should be 

directed to the Division of Compliance (HFV-230) at 240-

276-9200.

5.9.8 – PRODUCTS INTENDED FOR 

CONTROL OF FLEAS AND TICKS

Products for animal use intended for control of fleas and 

ticks may be regulated as drugs by FDA under the Federal 

Food, Drug, and Cosmetic Act or pesticides by the 

Environmental Protection Agency (EPA) under the Federal 

Insecticide, Fungicide, and Rodenticide Act. Products 

registered with EPA as pesticides must have an EPA 

registration number listed on the label. Questions 

regarding whether a product intended for control of fleas 

and ticks is regulated by FDA or EPA should be directed 

to CVM, Division of Drug Compliance at 

CVMCompliance@fda.hhs.gov. Questions regarding 

EPA-registered pesticide products should be referred to 

EPA at pesticidequestions@epa.gov or Environmental 

Protection Agency, Office of Pesticide Programs, 1200 

Pennsylvania Ave., Washington, DC 20460.

SUBCHAPTER 5.10 – BIORESEARCH 

MONITORING (BIMO)

Inspectional activities in the bioresearch monitoring (BIMO) 

program involve all product areas and centers. 

Establishments inspected include Sponsors, Monitors, 

Contract Research Organizations, Clinical Investigators, 

Sponsor-Investigators, Institutional Review Boards, In Vivo 

Bioequivalence / Bioanalytical Clinical and Analytical Sites, 

and Nonclinical Laboratories. BIMO also includes Post 

market Adverse Drug Experience (PADE) reporting and 

Risk Evaluation and Mitigation Strategies (REMS), both of 

which are post approval activities. BIMO inspections are 

conducted to determine the reliability of data submitted in 

support of premarket and pre-license applications as well 

as to ensure the rights and safety of research subjects are 

protected.

5.10.1 – BIMO Establishment Type

Definitions

Clinical Investigator – A person who conducts a research 

study (i.e., recruits study subjects, administers the 

investigational product to humans or animal subjects or 

uses a device on subjects, prepares and maintains case 

history reports, etc.).

Contract Research Organization (CRO) – An entity 

employed or contracted by sponsors or CROs to oversee 

the progress of an investigation. A monitor is not a 

regulated entity unless they have assumed one or more 

obligations from the sponsor in writing. In such case, the 

monitor is regulated as a contract research organization.

 

Institutional Review Board – Also known as Institutional 

Review Committee for Human Studies and Ethics 

Committee internationally. An IRB reviews protocols for 

studies and evaluates informed consent documents and 

risk/benefit decisions made regarding study procedures. 

An IRB may or may not be affiliated with an institution such 

as a hospital.

In Vivo Bioequivalence/Bioanalytical Clinical Site – A 

facility or individual involved in the screening and/or dosing 

of human subjects for obtaining biological specimens (e.g., 

blood, saliva, urine, feces) for analysis of investigational 

product content to define absorption, distribution, 

metabolism and/or elimination characteristics of the 

investigational product or to establish its equivalency with a 

defined standard. 

In Vivo Bioequivalence/Bioanalytical Analytical Site – A 

laboratory involved in the analytical testing of human 

biological specimens for levels of investigational product

content or the in vitro testing of investigatational products

to establish equivalency with a defined standard. These 

facilities may be integrated with or separate from clinical 

sites obtaining human specimens.

Nonclinical Laboratory – A laboratory that conducts in 

vivo or in vitro experiments in which investigational 

produccts are studied prospectively in test systems under 

laboratory conditions to determine their safety. Nonclinical 

studies do not include studies utilizing human subjects or 

clinical studies or field trials in animals. Nonclinical studies 

also do not include basic exploratory studies carried out to 

determine whether an investigational product has any 

potential utility or to determine physical or chemical 

characteristics of an investigational product.

Sponsor – A person or establishment that initiates, 

supports and usually monitors an investigational study on 

FDA regulated products, but who does not actually conduct 

the study.

Sponsor-Investigator – A clinical investigator who is also 

responsible for initiating an investigational study. This 

person has the responsibilities of both a sponsor and a 

clinical investigator.

Postmarket Adverse Drug Experience (PADE) – PADE 

inspections are conducted at pharmaceutical 

establishments, which may be the manufacturing site, but 

most often are at a corporate headquarters facility. The 

inspection is conducted where the complaint handling 
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unit/department responsible for evaluating and reporting 

adverse drug events is located. The purpose of the 

inspection is to ascertain whether the firm is complying with 

the evaluation and reporting requirements.

Risk Evaluation and Mitigation Strategies (REMS) - A 

(REMS) is a required risk management plan that uses tools, 

as specified in Food and Drug Administration Amendments 

Act of 2007 (FDAAA), beyond routine professional labeling 

(the package insert) necessary to ensure that the benefits 

of a drug outweigh its risks. The purpose of a REMS 

inspection is to verify the REMS is implemented and 

functioning in accordance with the FDA approved REMS 

and to verify information in the REMS assessment report.

Radioactive Drug Research Committee (RDRC) –An 

Institutional Review Board subcommittee or branch, which 

is FDA approved, who reviews and approves certain 

research uses of radioactive drugs that are generally 

recognized as safe and effective (GRASE.)

5.10.2 – BIMO Assignments

Assignments are issued by the product centers to ORA. 

These assignments are primarily issued to conduct 

inspections of entities engaged in nonclinical or clinical 

research and were involved in studies submitted as part of 

an application for approval of new product. Typically, 

inspections are conducted well after a nonclinical or clinical 

study has been completed. Inspections may also be 

conducted of on-going research. Assignments may also be 

issued for-cause for allegations for potential 

noncompliance and to conduct investigations and sample 

collections.

Each assignment will identify the establishment type to be 

inspected. In BIMO, the Compliance Programs are based 

upon the establishment type to be inspected and provide 

instruction on what to cover during the inspection. The 

areas of coverage relate to the specific regulatory 

requirements of each establishment type.

Assignments are prepared by each center using a template 

that was harmonized across all centers for the BIMO 

program. The assignment memo will identify the type of 

establishment to be inspected, the Compliance Program, 

the Program Assignment Code, background information, 

general instructions and any special instructions for 

inspectional coverage. Assignments are issued to ORA 

HQ, reviewed and assigned to the appropriate division. 

Assignments are received by the Director, Investigations 

Branch and then disseminated to the appropriate 

supervisory group for assignment to an investigator.

Occasionally, center personnel will participate in 

inspections with field investigators. Center personnel are 

subject matter experts on the products or processes which 

are the focus of the nonclinical or clinical research. In these 

cases, the ORA investigator will be the lead investigator. 

See IOM 5.1.2.5 – Team Inspections.

Assignments in BIMO will usually have background 

materials, which will be available to you via a link to 

Enterprise Content Management Server/System (ECMS). 

Background materials may include the protocol for the 

study you are assigned to inspect, certain line listing of data 

included in the application such as reported adverse events 

and measurements taken during the study, and the 

assignment memo. If there are specific areas to focus on 

during the inspection, the assignment memo will discuss 

these areas and there may be specific data included in the 

background materials for you to verify during your 

inspection.

Centers have final classification authority for inspections in 

the BIMO program. When inspections are completed and 

the EIR reviewed by your supervisor, an initial inspection 

classification will be assigned through eNSpect. The 

centers will determine and assign the final classification for 

the inspection after their review of the EIR and evidence 

collected is completed.

5.10.2.1. READ-ONLY ACCESS TO 

ELECTRONIC DATABASES DURING 

BIORESEARCH MONITORING INSPECTION 

ASSIGNMENTS

As the conduct of clinical and non-clinical trials 

increasingly moves toward 100% electronic data capture, 

to include electronic case report forms, medical records, 

patient-reported outcomes, informed consent systems and 

other electronic study records, it has become necessary 

for bioresearch monitoring investigators to have access to 

these electronic systems and databases in order to 

successfully perform inspections. Overseeing the firm’s 

personnel while they access their system is not always 

practical in BIMO inspections, as this can result in the firm 

having to dedicate an individual to this task. 

For these reasons, if all the following criteria are met, 

bioresearch monitoring investigators are permitted to 

access a firm’s records via a read-only account, dummy 

terminal or comparable mechanism when necessary:

1. Responsible management at the firm is agreeable 

to allowing read-only access to electronic systems 

and/or databases;

2. Access to electronic systems/databases is readonly and will not permit you to change or alter 

data or programming in any manner;

3. You obtain written program supervisory approval 

to gain read-only access to the firm’s electronic 

systems/databases in advance of doing so;

4. The firm has a representative that will be available 

to initially describe and review the layout of their 

records, and make themselves available 

throughout the inspection as additional 

information or copies of records are needed; and

5. You document this read-only access in your 

establishment inspection report or investigational 

memorandum accordingly.
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While you may complete a form needed by the firm in 

order to obtain read-only access, such as an account 

request form, you will not sign such form as per 

section 5.1.2.3. You may acknowledge via email that 

you have completed any required training necessary 

for access. When signing in to access a system, you 

may check a box and/or enter your name in order to 

acknowledge/accept the user agreement.

5.10.2.2 ELECTRONIC REGULATORY NOTES 

FOR BIMO OPERATIONS

As per section 1A.1.4.3, regulatory notes may be either 

handwritten in a bound notebook or in electronic format. 

eNSpect will be used for all electronic regulatory notes in 

the BIMO program.

5.10.3 – BIMO Compliance Programs

BIMO Compliance Programs are posted on the internet at: 

https://www.fda.gov/inspections-compliance-enforcementand-criminal-investigations/compliance-programguidance-manual-cpgm/bioresearch-monitoring-programbimo-compliance-programs

Compliance Programs in BIMO are designed to focus on 

the establishment type as clinical and nonclinical research 

crosses all product areas.

7348.003 In Vivo Bioavailability-Bioequivalence Studies–

Clinical

7348.004 In Vivo Bioavailability-Bioequivalence Studies–

Analytical

7348.808 Good Laboratory Practice (Nonclinical 

Laboratories)

7348.808A Good Laboratory Practice Program (Nonclinical 

Laboratories) EPA Data Audit Inspections

7348.809 Institutional Review Board

7348.809A Radioactive Drug Research Committee

7348.810 Sponsors and, Contract Research Organizations

7348.811 Clinical Investigators and Sponsor- Investigators

7353.001 Postmarketing Adverse Drug Experience (PADE) 

Reporting Inspections

7353.001C Risk Evaluation and Mitigation Strategies 

(REMS) Reporting Inspections

5.10.4 – Postmarket Adverse Event Reporting

FD&C Act section 760 [21 U.S.C. 379aa] and 21 CFR 

sections 310.305, 314.80, 314.98, 314.540, and 329.100 

require reporting of adverse events associated with the use 

of human drug products and section 600.80 requires 

reporting of adverse events associated with the use of 

biological products (including therapeutic biological 

products). Responsible firms include holders of 

applications (NDAs, ANDAs, or BLAs) and manufacturers, 

packers and distributors that are named on the labels of all 

FDA approved drug products, all prescription drug 

products, and OTC monograph drug products. Both foreign 

and domestic firms are required to develop written 

procedures and to maintain records related to adverse 

events. Firms must evaluate adverse event data to 

determine if the event has had a serious outcome such as 

death, disability, hospitalization, or was a life-threatening 

event, and if the event was expected (labeled) or 

unexpected (unlabeled) for the product. Responsible firms 

must submit adverse event information to FDA in expedited 

or periodic reports in an electronic format as described in 

the regulations. Adverse event information submitted to 

FDA should be complete and accurate based on the data 

received. 

Refer to the Compliance Program Guidance Manual (CP) 

(section 7353.001) for the description of the program and 

for detailed instructions for conducting inspections.

5.10.5 - Risk Evaluation and Mitigation 

Strategies (REMS)

FD&C Act Section 505-1 [21 U.S.C. 355-1] gives the FDA 

the authority to require Risk Evaluation and Mitigation 

Strategies (REMS) for certain drugs to ensure that the 

benefits outweigh the risks. REMS are required risk 

management plans that use risk minimization strategies 

beyond the professional labeling to ensure benefits of 

certain prescription drugs outweigh their risks. An applicant 

may be required to establish a REMS as part of the 

approval process (or when new safety data for an approved 

product arises), and an inspection will focus on the 

applicant’s adherence to the REMS. Each REMS is unique, 

can be used for a single drug or class of drugs, and may 

include one or more of the following: a medication guide, 

communication plan, elements to assure safe use 

(ETASU), or implementation plan. REMS must also include 

a timetable for submission of assessments. 

REMS are subject to inspection and are enforceable under 

section 505 (o) of the FD&C Act as amended by FDAAA. 

REMS inspections are conducted to verify that the REMS 

is implemented and functioning according to the FDA 

approved REMS document and to verify the information 

provided to FDA in the REMS assessment report. Since 

every REMS program varies, the detailed instructions for 

conducting inspections will be given to the investigator prior 

to each inspection.

5.10.6 BIMO Establishment Inspection 

Reports (EIRs)
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In general, refer to IOM 5.11 for reporting requirements 

following BIMO inspections with a few exceptions as 

follows. The Summary of Findings format is not to be used 

for BIMO EIRs. For foreign inspections where the firm has 

been previously inspected and the recommended 

classification for the current inspection will be NAI, an 

abbreviated report may be used as per section 5.11.4.3.1 

under the heading Routine Surveillance—NAI Reports as 

outlined below.

Domestic BIMO EIRs and EIRs for foreign inspections not 

meeting the above criteria will utilize the Standard 

Narrative Report format but must also include content 

required by compliance programs and specific assignment 

instructions. This content should be included by adding 

the headings that are listed in the compliance program, 

e.g., Authority and Administration, Protocol, Institutional 

Review Board, Subjects’ Records, etc. for a clinical 

investigator inspection. 

There are a few section headings that may be deleted as 

they are not generally applicable to BIMO inspections. If 

you are creating your report within eNSpect and the 

system does not allow you to delete the heading, simply 

insert “N/A” within that section of the report. Headings that 

may be deleted for BIMO EIRs include: 

Manufacturing/Design Operations, Manufacturing Codes 

(may be applicable for Bioequivalence), and Recall 

Procedures. All other headings should be included. If they 

do not apply to your inspection (e.g., Sample Collection, 

Refusals), simply insert “N/A” into that section, but do not 

delete.

For foreign inspections where the firm has been previously 

inspected and the recommended classification for the 

current inspection will be NAI, the abbreviated report 

should include the information required in section 

5.11.4.3.1 Routine Surveillance—NAI Reports (to include 

change reporting) as well as the following:

BIMO program specific information (i.e., the data 

requested in post-inspection email summaries provided to 

center points of contact, with additional details that may 

add value to the review process and specific assignment 

instructions) including but not limited to the following (as 

applicable):

o Protocol – name, number, sponsor

o # Subjects 

Screened/Consented/Enrolled/Randomize

d/Completed (whichever descriptions fit 

best) 

o Records Reviewed (including Subjects) 

and Recordkeeping Practices

o Adverse events

o Primary Endpoints

o Discussion items (including minor protocol 

deviations or recordkeeping issues)

5.10.7 BIMO Affidavits

Affidavits will be obtained in accordance with IOM 4.4.5. In 

the BIMO program, affidavits (FDA 463a) will generally be 

obtained to document violative conditions or unusual 

circumstances observed during an inspection. 

Additionally, an affidavit will accompany all sample 

collection reports, whether or not the firm provides a 

statement on company letterhead attesting that the test 

and reference product reserve samples are representative 

of those used in inspected BA/BE studies, and that they 

were stored under conditions specified in accompanying 

records, e.g. protocol or labeling. This is because all 

bioequivalence samples are official samples, and as such 

must be accompanied by an affidavit. 

5.10.8 BIMO Collection Reports (CRs)

Samples collected under the BIMO program primarily 

include bioequivalence samples. Refer to IOM 4.6 for 

reporting these sample collections. All subs collected for a 

bioequivalence sample including investigational product, 

reference, and placebo, will be included on one collection 

report. A scanned copy of the collection report and all 

associated documents will be uploaded into eNSpect as 

an attachment to the EIR.

Additional instructions specific to certain fields on BIMO 

CRs are as follows:

5.10.8.1 Sample Type

The sample type for all bioequivalence samples will be 

“Official”. Select “Domestic-Import” if applicable. Note: 

Domestic-Import samples are also Official, however, this 

is the way the drop-down menu is set up. 

5.10.8.2 Sample Description

Ensure that the field includes a description of the 

investigational product collected as well as the reference 

and placebo if applicable.

5.10.8.3 Reason for Collection

Reference the compliance program (e.g., CP 7348.003, 

“In vivo Bioavailability- Bioequivalence Studies- Clinical”, 

the assignment memo, and the inspection dates (if 

applicable). There will not be a suspected violation for 

surveillance samples. Add the following statement and 

edit as appropriate, “Sample of bioequivalence 
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investigational product, reference control and placebo. 

Sample is representative of test product used in study 

supporting Protocol (insert Study #).” You will specify the 

analysis desired as follows: “Collected for drug assay 

analysis.” Include the application number, e.g., ANDA 

12345.

5.10.8.4 Associated Firms

List all firms related to the investigational product. 

Associated firms for the reference and placebo can be 

listed in the Collection Remarks field or on a continuation 

sheet.

5.10.8.5 Product Code and Product Name

The product code and product name listed should be that 

of the test article.

5.10.8.6 Brand Name

List the brand names for the test article, reference and 

placebo (if applicable.)

5.10.8.7 Product Label

Quote the label and labeling from the test article, 

reference and placebo (if applicable.) Be sure to use 

Collection Remarks or a continuation if necessary and 

specify which labeling goes to which product.

5.10.8.8 Sample Flags

There should be no sample flags for bioequivalence 

samples, unless the sample is a complaint sample. This is 

rare.

5.10.8.9 Estimated Value

It may be difficult to estimate the value of a bioequivalence 

sample. If the firm is not able to provide you with the value 

of the lot remaining after sampling, use the estimated cost 

of the innovator if possible. If you cannot estimate, leave 

blank and note in the Collection Remarks, “Estimated 

Value is unknown.”

5.10.8.10 CR & Records Sent To FACTS Org

For domestic CRs, select your division from the list of 

values and send the hard copy CR and all associated 

documents to the director of investigations for your 

division when complete. For samples collected on foreign 

inspections, select the appropriate center/division (e.g. 

CDER-CP for bioequivalence samples) from the dropdown menu and send the hard copy CR and all associated 

documents to the center/division office contact specified in 

the assignment memorandum.

SUBCHAPTER 5.11 – REPORTING

Following an inspection, you are required to prepare a 

report of your findings. Reporting includes the data and 

summary entered using eNSpect, a narrative report, 

attachments and exhibits. As soon as practical you have 

access to eNSpect after the close of an inspection, ensure 

the start and end date are entered. Investigators must 

select a suggested “Inspection Conclusion” in eNSpect for 

each process covered.

Reports must be completed within time frames 

commensurate with the inspection classification, the 

current regulatory action time frames for the anticipated 

regulatory action, applicable FMDs, SOPs, RPM and/or the 

assignment deadline, if any. 

Your narrative report should be prepared to accurately and 

concisely communicate the findings of your inspection and 

be adequate for its intended use. For example, an 

inspection of a new firm, one that FDA has not inspected 

previously, should be a comprehensive inspection focused 

on assessing the firm’s compliance with applicable 

regulations. The resulting report would detail the products 

manufactured, the processes used to manufacture those 

products, the conditions of the environment in which 

products are manufactured or stored, any violations 

observed, persons responsible for the firm’s operations, 

their actual duties and their responsibility for observed 

violations, distribution practices, and so on, providing 

information responsive to each of the required elements.

For establishments that have been previously inspected, 

you should determine what changes in operations and 

responsible individuals have occurred since the previous 

inspection, detail those changes in the narrative report and 

report on the areas of concern for the current inspectional 

outcome. For example, a non-violative inspection may only 

require a Summary of Findings report with the information 

required in the Summary, Administrative Data, General 

Discussion with Management, Voluntary Corrections, 

Refusals, Samples Collected, Exhibits Collected and 

Attachments (see IOM 5.11.4.1).

An OAI follow-up inspection that reveals continuing 

violations supporting a regulatory action would require the 

Summary, Administrative Data, Individual Responsibility 

and Persons Interviewed, Objectionable Conditions and 

Management’s Response, Supporting Evidence and 

Relevance, Discussion with Management, Exhibits 

Collected, Attachments, and if appropriate, Refusals, 

Samples Collected, and Voluntary Corrections. 

Additionally, any information related to changes in previous 

operations would also need to be included in this type of 

report.
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The key for you to remember in writing your narrative report 

is to communicate the findings of your inspection so that 

others may take the appropriate action. Notice that the 

required elements always include the product, interstate 

commerce, the violations observed and responsibility of 

firm officials. This is to document the elements of proof – 

Jurisdiction, Interstate Commerce, Violation and 

Responsibility (JIVR). Write your EIR with the intended use 

in mind. Your report may be a brief summary of an 

inspection of a firm in a state of compliance with applicable 

regulations all the way to a firm where the agency must take 

regulatory action to correct deficiencies. 

5.11.1 - ESTABLISHMENT INSPECTION 

REPORT (EIR)

See IOM 1.1 English language requirement. The EIR 

consists of the following: the eNSpect Establishment 

Inspection Report, investigator’s narrative report, 

attachments and exhibits. Regarding the use of checklists 

that are completed during the inspection (such as the BSE 

Checklist), the original checklist should be submitted with 

unlabeled attachments. If you maintain the data in your 

regulatory notes, instead of entering the data directly on the 

checklist during the inspection, then a copy of the checklist 

that was completed using the data from your regulatory 

notes should be included with the EIR. The signed original 

report is maintained electronically and is available in OSAR.

See IOM 5.10.6 for additional requirement for Bioresearch 

Monitoring EIRs.

See SOP-000063 “Submission and Processing of 

International Food Inspection and Investigation Reports” for 

additional information regarding the processing of foreign 

food reports.

5.11.2 – ENDORSEMENT

Supervisory Investigators evaluate inspection findings, 

determine the classification of the inspection, and 

recommend an action, in accordance with applicable 

compliance programs, assignments or policy. The final 

content of the endorsement of the establishment inspection 

report is determined by the supervisory investigator. 

However, Investigators should prepare proposed 

endorsement for their supervisor. Endorsements should fit 

in the available space provided in eNSpect, however, if the 

endorsement exceeds the character space provided in 

eNSpect, a separate endorsement should be prepared, 

fully identifying the firm with a summary of the endorsement 

included in eNSpect. The eNSpect endorsement field 

should identify that a separate endorsement has been 

prepared and uploaded to eNSpect. The eNSpect Record 

will be used as the endorsement and routing document to 

accompany the EIR. See also IOM 5.11.4.1.

Normally the endorsement consists of:

1. The reason for the inspection, i.e., workplan, or 

assignments from headquarters. State the subject of 

the assignment and reference. 

2. A brief history of previous findings (e.g., FDA 483 

observations, FDA 4056 observations, and discussion 

items) including classification of previous inspection, 

any action taken by the program division and/or 

corrective action taken by the firm in response to 

inspectional observations from the previous inspection.

3. A concise summary and evaluation of current findings 

and samples collected.

4. Refusals, voluntary corrections or promises made by 

the firm's management.

5. Identify FDA received consumer complaints covered 

during inspections and follow up disposition. 

6. Classification and follow-up consistent with 

inspectional findings and in accordance with applicable 

compliance program, assignments, or policy. Action 

may include notification of other program divisions and 

headquarters as warranted.

7. Distribution consistent with program division policy and 

the requirements of the specific compliance programs 

and requirements as noted in IOM 1.7.3. 

Note: When endorsing in eNSpect, include notification to 

the Division of Import Operations and Management (DIOM) 

when any violative, imported products are identified. 

Note: In rare situations (e.g., extended leave, retirement, 

deployment) a participant may not be available to sign the 

EIR. The supervisor should state in the endorsement 

“endorser acknowledges the inability of the participant to 

sign the EIR due to unavoidable circumstances”. (See 

section 5.11.4.3.21)

The existence of Personal Safety Alerts (IOM 5.2.1.3) or 

Personal Safety Plans (IOM 5.2.1.4) pertaining to the firm 

should be included in the endorsement section only and not 

in the EIR. 

The signed endorsement should be updated to indicate if 

an amendment to the EIR (IOM 5.11.7) or an amended FDA 

483 or and FDA 4056 (IOM 5.2.3.1.6.1 and 5.2.3.1.6.2) has 

occurred. PROFILES: Updating eNSpect with the 

Compliance Status for each profile class code associated 

with the firm's operations and/or products, is the 

responsibility of ORA Field Investigators, Supervisors and 

Compliance Officers from ORA and Centers. 

See Exhibit 5-14 for more information on profiling 

CGMP/QS Compliance Status.

5.11.2.1 – Reporting Verified Corrective 

Actions

A compliance achievement, also known as a verified 

corrective action, is the observed repair, modification, or 

adjustment of a violative condition, or the repair, 

modification, adjustment, relabeling, or destruction of a 
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violative product when either the product or condition does 

not comply with the Acts enforced by the FDA.

Both FACTS and eNSpect are used to report verified 

corrective actions, which are not the result of legal action. 

When you are unable to enter the action in eNSpect 

because the PAC is not available or the 483 was issued 

outside of eNSpect, investigator should enter corrective 

actions into FACTS CARS as directed in 5.11.2.1.1. 

The supervisor may enter the correction if the investigator 

is unavailable.

5.11.2.1.1 - REPORTING CRITERIA

There are three criteria for reporting into the FACTS CARS 

system:

1. The detection or identification of the problem. A problem 

may be observed by FDA, other federal officials, or by 

state or local authorities and referred to FDA; and as a 

result of an inspection, investigation, sample analysis, 

or detention accomplished by ORA or states under 

contract to ORA.

2. The correction of the problem. The correction is directly 

attributable to the efforts of ORA or state officials under 

contract to ORA (involving contract products only); and 

is unrelated to the filing of a legal action, i.e., seizure, 

prosecution, injunction.

3. The verification of the correction of the problem. The 

correction is verified by the FDA, other federal officials 

or state or local authorities and reported in writing to the 

FDA; and is based on an inspection, investigation, 

sample analysis, or letter from a firm to FDA certifying 

the problem has been corrected.

5.11.2.1.2 - DATA ELEMENTS

For instruction on entering corrective actions in eNSpect 

refer to the user manual. 

For instruction on entering corrective actions in FACTS 

see Exhibit 5-15. 

Only when the corrective action(s) has been verified should 

a FACTS CARS be reported. The data elements are those 

entered/coded in FACTS (See IOM Exhibit 5-15):

1. PAC. Should there be insufficient space to code all 

corrections verified on an occasion, record the most 

significant corrections.

2. PROBLEM TYPE. The problem type is the problem(s) 

identified during the operation(s). Use the List of Values 

(LOV) found in this field on the Compliance 

Achievement Reporting Screen. If “Other” is chosen, 

you should include an explanation in the “Remarks” 

field.

3. CORRECTIVE ACTION. The action the establishment 

took to correct the identified problem. Use the LOVs 

found in this field on the CARS screen. If "Other" is 

selected, you should include an explanation in the 

"Remarks" field.

4. VERIFICATION DATE. Use the date the corrective 

action(s) is verified, either through an establishment 

inspection, an investigation, or a letter from the 

establishment certifying the corrections have been 

made. Include documentation to verify the action such 

as repair receipts/plans.

5. CORRECTING ORGANIZATION. The FDA, other 

federal agency, or state or local authority, which 

observed the verified correction. Use the LOVs found in 

this field on the CARS screen.

6. REPORTING ORGANIZATION. The FDA, other federal 

agency, or state or local authority, which is actually 

inputting the verified correction. Use the LOVs found in 

this field on the CARS screen.

7. REASON FOR CORRECTION. The action the FDA took 

to make the correction happen. Use the LOVs found in 

this field on the CARS screen. If “Other” is chosen, you

should include an explanation in the “Remarks” field.

5.11.3 – eNSpect ESTABLISHMENT 

INSPECTION REPORT COVERSHEET

Per SOP-000051, each ORA Program Division and HQ 

Office is responsible to ensure all investigators verify, 

correct, and enter changes to the OEI (including Profile 

data for profilable firms) on the firm’s maintenance 

screens in eNSpect during each inspection, investigation 

and during any OEI update. Consult with your supervisor 

and your OEI Coordinator to assure data is accurately 

updated. 

Inspectional accountable time reported into eNSpect 

consists of the hours devoted to file reviews (operational 

preparation), actual onsite inspectional time, document 

preparation (attachments and exhibits) and EIR (narrative) 

write-up. Accountable time does not include travel time. 

One occasional exception could be when more than one 

participant prepares and discusses the assignment while 

they are traveling together.

You should report the actual amount of inspection 

accountable time it took you. Do not report the module 

time given in the ORA Workplan. Additional time required 

to complete the assignment due to giving or receiving 

training should be reported separately from inspectional 

time.

5.11.3.1 – Inspection Basis

The inspection basis is the underlying reason for 

conducting an inspection. 

Compliance – A directed inspection to evaluate potential 

violative situations that the agency has become aware of at 

the firm or industry and have not already resulted in an 

official agency action. These may include complaints 

(trade or consumer) which are not the primary reason for 

the inspection , recalls not classified as Class I, MedWatch 

Reports, Adverse Drug Experience Reports, information 

from confidential informants, etc.

Consumer Complaint – A directed inspection in which 

the primary purpose is to follow up on a complaint. 
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Complaints can be from multiple sources (e.g., 

consumers, industry, informants, whistleblowers). When a

complaint is received, and the follow-up action chosen is 

to conduct an inspection to confirm allegations within the 

complaint or root causes that may have led to the 

condition described in the complaint, this value should be 

selected.

Emergency Operations - An inspection that is 

conducted as a result of unplanned or unexpected work 

due to an emerging situation that requires immediate 

attention. This inspection basis should not be used if an 

inspection is due in the current fiscal year. 

F/U to Class I Recall – A directed inspection in response 

to a Class I Recall conducted by the establishment. The 

inspection is conducted to determine the root cause and 

corrective actions addressing the violation(s) associated 

with the product.

F/U to Class I Recall and F/U to Injunction – A directed 

inspection conducted in response to a Class I Recall 

conducted by the establishment AND pursuant to 

Permanent Injunction and in accordance with the Consent 

Decree. In this instance, a firm under permanent injunction 

has conducted a Class I Recall and the inspection is 

conducted to determine the root cause and corrective 

actions addressing the violation(s) associated with the 

product. Additionally, the inspection covers the 

requirements of the Consent Decree for the Injunction.

F/U to Class I Recall and F/U to Warning Letter – A 

directed inspection conducted in response to a Class I 

Recall conducted by the establishment AND to follow up 

on issues cited in a Warning Letter issued to the 

establishment. In this instance, a firm that has received a 

Warning Letter has conducted a Class I Recall and the 

inspection is conducted to determine the root cause and 

corrective actions addressing the violation(s) associated 

with the product in addition to covering corrective actions 

responsive to the violations cited in the Warning Letter. 

The Warning Letter may have issued as a result of the 

previous inspection or other circumstance.

F/U to Class I Recall and OAI Inspection F/U – A 

directed inspection conducted in response to a Class I 

Recall conducted by the establishment AND to follow up 

to a previous OAI-classified inspection, where a regulatory 

or administrative action has not been completed. This 

value captures the situation where the previous inspection 

of the firm was classified OAI, but no official action was 

taken, and the firm has conducted a Class I Recall. The 

inspection is focused on the root causes of the violations 

leading to the recall and may also address previously cited 

violations. Before conducting an inspection of a firm 

where the previous inspection was classified OAI with no 

regulatory action taken, be sure to discuss what areas to 

cover with your supervisor and/or compliance officer.

F/U to Injunction – An inspection conducted pursuant to 

Permanent Injunction and in accordance with the Consent 

Decree. 

F/U to Warning Letter – An inspection conducted to 

follow up on issues cited in a Warning Letter issued to the 

establishment. This inspection is focused on the firm’s 

actions to resolve issues cited in the Warning Letter. 

OAI Inspection F/U – An inspection conducted to followup previous OAI-classified inspection where a regulatory 

or administrative action has not been completed. There 

can be a number of situations where an action is not taken 

although the observations cited during the previous 

inspection met the threshold for an OAI classification. 

Consult your supervisor and/or compliance officer prior to 

initiating these types of inspections. 

Surveillance – An inspection conducted as a routine 

assignment with no other indicators of non-compliance. 

For example, an inspection of a firm whose previous 

inspection was classified NAI; there have not been any 

complaints or recalls, etc.

5.11.4 - NARRATIVE REPORT

See IOM 1.1, English language requirement. You should 

use eNSpect for all EIRs. The narrative report is the written 

portion of the EIR, which accurately describes the 

investigator's inspectional findings. The narrative report 

may be prepared in two formats depending on the type of 

inspection and inspection classification. A Summary of 

Findings narrative report may be used for NAI and VAI

classified, non-initial inspections (IOM 5.11.4.1 and IOM 

5.11.4.2), or as directed by your supervisor. The full 

Standard narrative report is used for initial and potential 

Official Action Indicated (OAI) classified inspections (IOM 

5.11.4.3.1). Additional requirements for human drug and 

medical device establishment inspection reports are 

described in IOM 5.5.8 and 5.6.9. For all reporting formats, 

include additional information as directed by your 

assignment, Compliance Program Guidance Manual, or 

your Supervisor.

EIRs populated in eNSpect should automatically include 

the firm name and FEI. those populated outside of 

eNSpect should include the firm name, FEI in the header 

and the footer should include the page number.

All reports should be prepared or uploaded into eNSpect. 

Your Establishment Inspection Report (EIR) should:

1. Be factual, objective, and free of unsupportable 

conclusions.

2. Be concise and descriptive while covering the 

necessary aspects of the inspection.

3. Not include opinions about administrative or regulatory 

follow-up.

4. Not Include information that could identify confidential or 

anonymous informants (See IOM 5.2.9.2)

5. Generally, be written in the first person using the active 

voice. 

6. Be signed by all FDA and commissioned personnel 

participating in the inspection. See IOM section 

5.1.2.5.1 when more than one FDA or commissioned 

person participated in the inspection. 

Refer to IOM 5.11.7 for an Amendment to EIR.
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5.11.4.1 – Summary of Findings report for 

NAI Inspections

Investigators should use "Summary of Findings", standalone, narrative reports for NAI domestic establishments, 

unless otherwise directed by your supervisor, the 

assignment or the Compliance Program Guidance Manual.

Use the report format given in 5.11.4.3.1- Standard 

Narrative Report, Comprehensive Reports- for all foreign 

inspections. For BIMO inspections, see 5.10.6.

The Summary of Findings Report may not be written solely 

in the eNSpect provided "Inspection Summary" heading. 

The Summary of Findings report should include:

1. The reason for the inspection;

2. The date, final classification and findings of the previous 

inspection;

3. The actual inclusive dates of the inspection (these may 

be included as part of a header or in the body of the 

EIR.)

4. Report the current registration(s) status or any changes 

to registration status. Per CPG section 110.300, do not 

report the FURLS Registration number.

5. The name of the person to whom credentials were 

shown and the FDA-482, Notice of Inspection or FDA 

482d Request for FSVP Records was issued and the 

person's authority to receive the FDA 482 or 

FDA 482d. Explain if you were unable to show 

credentials or issue forms to top management. Include 

the name of the person to whom the FMD-145 

correspondence should be directed to and their email 

address. If an email address does not exist for this 

person, then this should be noted.

6. The inspectional approach (comprehensive or directed); 

the scope of the inspection; a brief description of the 

business; a description of the products produced; and a 

brief description of the products, processes or systems 

covered during the inspection. Indicate which aspects of 

the firm’s processes or systems you observed versus 

those which the firm described to you;

7. The manufacturing codes and if necessary their 

interpretation.

8. Significant changes (e.g., personnel, facilities, products, 

processes) since the previous inspection;

9. Voluntary Corrections

10.Samples collected

11.Exhibits collected;

12.Attachments

13.The investigator's signature.

5.11.4.2 – Summary of Findings for VAI 

Inspection

Investigators should use "Summary of Findings", 

standalone, narrative reports for VAI domestic 

establishments, unless otherwise directed by your 

supervisor, the assignment or the Compliance Program 

Guidance Manual. Use the report format given in 

5.11.4.3.1 - Standard Narrative Report, Comprehensive 

Reports for foreign inspections.

All violative EIR's should in addition to the information 

required for non-violative reports contain the following: 

1. The objectionable conditions or practices described in 

sufficient detail so someone reading the report will 

clearly understand the observation(s) and significance. 

2. The objectionable conditions or practices crossreferenced to FDA 483 or FDA 4056 citations, samples 

collected, photographs, or other documentation 

including exhibits attached to the EIR. 

3. Information as to when the objectionable conditions or 

practices occurred, why they occurred, and who is or 

was responsible, developed to the highest level in the 

firm. 

5.11.4.3 - Individual Narrative Headings

There are many acceptable ways of organizing a narrative 

report. The key is to cover the required information in IOM 

5.11.4, 5.11.4.1 and 5.11.4.2, or as required by the 

assignment, Compliance Program Guidance Manual, or 

your supervisor. The appropriate use of headings should 

not result in repetition of the same information in different 

sections. You are encouraged to create headings as 

necessary to present the inspectional findings in the most 

concise manner. For NAI and VAI classified inspections, a 

single heading such as “Summary of Findings” is sufficient 

(for exceptions, see IOM 5.11.4.1 and 5.11.4.2). eNSpect

should be used to generate the FDA 483, FDA 483a, and 

FDA 4056. In certain instances, if you experience computer 

problems, do not delay the issuance of the FDA 483, FDA 

483a, or FDA 4056. See IOM 5.2.3. You should use 

eNSpect for all EIRs.

5.11.4.3.1 - STANDARD NARRATIVE REPORT

This is intended to outline the minimal information needed 

to produce a narrative report that supports further agency 

regulatory action, as warranted. Investigators are 

encouraged to add additional report headings as needed to 

communicate important information about the inspection, 

relevance of inspectional observations that may impact 

public health, and /or to address specific requests from 

directed assignments.

Comprehensive Reports (Include all applicable 

sections)

A comprehensive EIR should be prepared for initial 

inspections as well as foreign inspections in all program 

areas. It is essential to describe the products manufactured, 

the process the manufacturing and storage environment, 

distribution patterns/interstate commerce, individual 

responsibility of key employees, history of business, all 

objectionable conditions observed, etc. All things pertinent 

to the operations and management of the establishment 

should be included in these reports. The comprehensive 

report may also be used for other situations requiring full 

reporting such as Routine Surveillance - OAI. An 

abbreviated inspection does not necessarily equate to an 

abbreviated report.

Required elements
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• 5.11.4.3.2 – Summary 

• 5.11.4.3.3 – Administrative data 

• 5.11.4.3.4 – History 

• 5.11.4.3.5 – Interstate (I.S.) Commerce 

• 5.11.4.3.6 – Jurisdiction (Products Manufactured 

and/or Distributed) 

• 5.11.4.3.7 – Individual Responsibility and Persons 

Interviewed

• 5.11.4.3.8 – Firm’s Training Program 

• 5.11.4.3.9 – Manufacturing/Design Operations 

• 5.11.4.3.10 – Manufacturing Codes 

• 5.11.4.3.11 – Complaints 

• 5.11.4.3.12 – Recall Procedures 

• 5.11.4.3.13 – Objectionable Conditions and 

Management’s Response 

• 5.11.4.3.13.1 – Supporting Evidence and 

Relevance 

• 5.11.4.3.13.2 - Discussion with Management 

• 5.11.4.3.14 – Refusals 

• 5.11.4.3.15 – General Discussion with 

Management 

• 5.11.4.3.16 – Additional Information 

• 5.11.4.3.17 – Samples Collected 

• 5.11.4.3.18 – Voluntary Corrections 

• 5.11.4.3.19 – Exhibits Collected 

• 5.11.4.3.20 – Attachments

Routine Surveillance – NAI Reports

When FDA has an inspectional history for the firm and no 

deficiencies were observed by the investigator, a brief 

report may be prepared. The intent of this report is to 

include only the required information about the firm and 

what areas were covered during the inspection. “Change 

reporting” means information that differs from the previous 

inspection report such as changes in management, 

products produced, manufacturing processes, etc. Where 

these changes have occurred, the applicable section 

heading in the EIR should be included. The elements may 

also be captured in a “Summary of Findings Only” report 

without header information. See IOM 5.11.4.1.

Required elements

• 5.11.4.3.2 – Summary 

• 5.11.4.3.3 – Administrative data

• 5.11.4.3.10 – Manufacturing Codes

• 5.11.4.3.14 – Refusals 

• 5.11.4.3.15 – General Discussion with 

Management

• 5.11.4.3.17 – Samples Collected 

• 5.11.4.3.18 – Voluntary Corrections 

• 5.11.4.3.19 – Exhibits Collected 

• 5.11.4.3.20 – Attachments

Change reporting only

• 5.11.4.3.4 – History 

• 5.11.4.3.6 – Jurisdiction (Products Manufactured 

and/or Distributed) 

• 5.11.4.3.7 – Individual Responsibility and Persons 

Interviewed 

• 5.11.4.3.8 – Firm’s Training Program 

• 5.11.4.3.9 – Manufacturing/Design Operations 

Routine Surveillance – VAI Reports

For firms with an inspectional history and the outcome of 

the inspection is a VAI classification, the below elements 

would be required, plus change reporting. Note that the 

difference in the NAI versus the VAI report is the inclusion 

of narrative addressing objectionable conditions observed 

during the inspection. Each objectionable condition or 

practice must be documented in the EIR along with 

discussion of the evidence, relevance and discussion with 

management.

Required elements 

• 5.11.4.3.2 – Summary 

• 5.11.4.3.3 – Administrative data 

• 5.11.4.3.10 – Manufacturing Codes

• 5.11.4.3.13 – Objectionable Conditions and 

Management’s Response 

• 5.11.4.3.13.1 – Supporting Evidence and 

Relevance 

• 5.11.4.3.13.2 - Discussion with Management 

• 5.11.4.3.14 – Refusals

• 5.11.4.3.15 – General Discussion with 

Management

• 5.11.4.3.17 – Samples Collected 

• 5.11.4.3.18 – Voluntary Corrections 

• 5.11.4.3.19 – Exhibits Collected 

• 5.11.4.3.20 – Attachments

Change reporting only

• 5.11.4.3.4 – History 

• 5.11.4.3.6 – Jurisdiction (Products Manufactured 

and/or Distributed) 

• 5.11.4.3.7 – Individual Responsibility and Persons 

Interviewed 

• 5.11.4.3.8 – Firm’s Training Program 

• 5.11.4.3.9 – Manufacturing/Design Operations 

Routine Surveillance – OAI

For an OAI surveillance inspection, follow the guidance 

under Comprehensive Reports.

OAI Follow-up Inspection Reports

OAI follow-up inspections are inspections conducted 

following an OAI classified inspection. Inspections of this 

nature are conducted to determine whether corrective 

actions have been implemented or significant violations 

continue. The outcome of these inspections may range 
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from NAI to OAI. The intended use of the EIR should be 

the driving force of the content of these EIRs. Typically, 

the follow-up should be done relatively soon after the 

previous inspection, so changes to products, process, 

personnel, etc. should be minimal. The NAI and VAI 

reports should focus on corrective actions implemented by 

firm management to correct the violative conditions 

observed during the previous OAI inspection. Those 

reports may be Summary of Findings only or may follow 

the other NAI and VAI report formats above. An OAI 

follow-up inspection may lead to a regulatory action such 

as seizure, injunction and/or prosecution. Those reports 

should focus on documenting the continuing violations, 

responsibility for those violations, any corrective actions 

implemented or inadequate corrective actions and defining 

the new scope of violations observed including the 

products affected. Scope should include additional lots, 

products, timeframe and distribution. These reports should 

document all elements of JIVR (Jurisdiction, Interstate 

Commerce, Violation and Responsibility). This allows for 

the report to support whatever regulatory action is deemed 

necessary.

Required elements

• 5.11.4.3.2 – Summary 

• 5.11.4.3.3 – Administrative data 

• 5.11.4.3.7 – Individual Responsibility and Persons 

Interviewed

• 5.11.4.3.10 – Manufacturing Codes

• 5.11.4.3.13 – Objectionable Conditions and 

Management’s Response 

• 5.11.4.3.13.1 – Supporting Evidence and 

Relevance 

• 5.11.4.3.13.2 - Discussion with Management 

• 5.11.4.3.14 – Refusals

• 5.11.4.3.15 – General Discussion with 

Management

• 5.11.4.3.17 – Samples Collected 

• 5.11.4.3.18 – Voluntary Corrections 

• 5.11.4.3.19 – Exhibits Collected 

• 5.11.4.3.20 – Attachments

Change Reporting Only:

• 5.11.4.3.5 – Interstate (I.S.) Commerce 

• 5.11.4.3.6 – Jurisdiction (Products Manufactured 

and/or Distributed) 

• 5.11.4.3.9 – Manufacturing/Design Operations 

• 5.11.4.3.11 – Complaints

5.11.4.3.2 - SUMMARY

5.11.4.3.3 - ADMINISTRATIVE DATA

1. The firm name, address, phone, fax, website address,

and e-mail address of the firm

2. Report the names and titles of the Investigator(s), 

Analyst(s), non-FDA officials, etc. Report the name of 

the firm’s responsible official who gave permission to 

non-FDA officials without inspection authority to 

accompany you during your inspection. See IOM 5.1.1 

and 5.2.2.

3. The inclusive date(s) of the current inspection, i.e., list 

the actual dates in the plant.

4. If a team inspection and some individuals were not 

present during the entire inspection, indicate dates in 

plant for each team member.

5. For foreign inspections with Locally Engaged Staff 

(LES)/Foreign Service National (FSN) participation

include this language:

This inspection was supported by 

____________________ (during the period of 

__________), who is a Locally Engaged Staff (LES) 

hired by the United States Embassy and assigned to 

FDA to work in support of FDA activities. All information, 

including documents collected during this inspection and 

any translation from local language to English by 

______________(LES) that supports the Form FDA 

483, Inspectional Observations (if Form FDA-483 was 

issued), FDA 483a FSVP Observations, Form FDA 

4056, Produce Farm Inspectional Observations and the 

Establishment Inspection Report (EIR) was collected in 

collaboration with the FDA investigator(s).

Report:

1. Full names and titles to whom FDA Official Credentials 

were shown,

2. Full names and titles to whom any FDA forms were 

1. Provide the reason for the inspection including if it was

announced or unannounced (e.g., compliance 

program(s), by assignment number, trip number, etc.);

2. The inspectional approach (comprehensive or directed); 

the scope of the inspection; a brief description of the 

business; a description of processes used, and the 

products produced.

3. Provide a summary of the findings, date, and final 

classification of the previous inspection and the firm’s 

response/corrective actions.

4. List the products, profile, systems and processes 

covered during the current inspection, and the types of 

records and documents reviewed. For human drug 

reports, list all systems the firm has currently employed.

5. Provide a summary of the current findings (i.e., 

reportable observations, nonreportable observations, 

and discussion items), refusals, samples collected, 

warnings given to management, and a summary of 

management's response or voluntary corrections.
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issued to or signed by during the inspection (FDA 482, 

483, 484, 463, 4056, etc.); where appropriate, explain 

the reason a form(s) was not issued to or signed by the 

most responsible individual (this may be reported in the 

Individual Responsibility and Persons Interviewed 

heading below),

3. Full name, title, address (if different from the address 

of the inspected establishment), and email address of 

the top management official to whom the FMD 145 

letter should be addressed. If an email address does 

not exist for this person, then this should be noted. 

4. Full names, titles and addresses (if different from the 

address of the inspected establishment) of most 

responsible corporate official(s) to whom other 

correspondence, e.g., Warning letter, should be 

addressed 

5. If this was a team inspection, who wrote which section 

of the EIR. 

6. Full names and titles of inspectors from other 

government agencies (i.e. federal, state, local or 

foreign) at the facility during the inspection. 

7. Full names and titles of who provided translation of 

foreign language documents. 

8. If an inspection is conducted at premises also used for 

living quarters document that you are inspecting a 

residence and if the owner was agreeable. (IOM 5.1.1.9)

9. Full name and title of the individual provided with 

guidance documents and list the documents provided. 

5.11.4.3.4 - HISTORY

1. Report the legal status of the firm (corporation, 

partnership, limited liability company, sole 

proprietorship, etc.), and the state and year of 

incorporation.

2. List the parent corporation, corporate address and 

relevant subsidiaries with respective FEIs.

3. Provide a summary of any agency actions and prior 

warnings (do not cite any action only recommended but 

not approved). You should also report any significant/relevant inspectional history pertinent to the current 

EI or recommendation.

4. Include any relevant recalls, market withdrawal, etc. 

since the last inspection.

5. Report the hours of operation and any changes from 

past inspections (include seasonal variations).

6. Report all current registration(s) status or any changes 

to registration status. Describe any inaccuracies 

identified in the firm’s registration(s). Per CPG section 

110.300, do not report the FURLS Registration number.

7. Report if the firm is located on tribal land, or is 

owned/operated by a federally recognized Indian tribe 

or tribal member. 

5.11.4.3.5 - INTERSTATE (I.S.) COMMERCE

1. Report the estimate of the percentage of products 

shipped outside of the state (or exported to the U.S.) 

and the basis of the estimate.

2. Report the firm's general distribution patterns.

3. If there is an apparent violative product, provide 

examples of interstate shipments of violative product(s); 

or

4. If no such shipments, provide examples of interstate 

shipments of major components of apparent violative 

products - with complete interstate documentation in 

either case.

5. For foreign inspections, list significant U.S. consignees 

to whom the firm’s products are shipped.

6. For Human Drugs - domestic firms, identify the general 

types of customers and provide the names and 

addresses for several regular customers of a few of the 

firm’s products.

5.11.4.3.6 - JURISDICTION (PRODUCTS 

MANUFACTURED AND/OR DISTRIBUTED)

1. Include a list of a representative number of currently 

marketed products in all program areas subject to 

FD&C Act or other statute enforced by FDA or 

counterpart state agency, including any believed 

violative.

2. Collect appropriate labeling (product and case labels, 

inserts, brochures, manuals, promotional materials of 

any type) for those products believed violative or representing any significant new or unusual operation, industry or technology; or as directed by your supervisor.

3. Report the firm’s general promotion patterns (i.e. 

website, advertisements, etc.).

4. Document any applicable labeling agreements (and 

obtain a copy) and statutory guaranty given or received 

per Sections 301(h) and 303(c)(2) of the FD&C Act [21 

U.S.C. 321 (h) and 333 (c)(2)] (IOM 5.3.7.2)

In addition, the label, labeling and promotional materials are 

a critical part of determining a product’s intended use.

1. In instances where a regulatory action is being 

considered based on product labels, labeling, and/or 

other promotional materials, including any Internet 

websites, you should collect all available 

documentation. This includes all written, printed or 

graphic matter on the immediate container of an article 

or accompanying the article (the product’s label and 

labeling, see FD&C Act, 201(k) and (m) [21 U.S.C. 

321(k) and (m)] and IOM 4.4.7.1). Accompanying 

labeling could include brochures, pamphlets, circulars, 

and flyers, as well as audio and video tapes.

2. In cases where there may be a dispute about whether a 

product is a drug or a dietary supplement, you should 

collect all materials which claim a product can be used 

for the treatment of any disease.
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5.11.4.3.7 - INDIVIDUAL RESPONSIBILITY 

AND PERSONS INTERVIEWED

Report with whom you dealt, and in what regard (both 

during and prior to the start of the inspection):

1. Who provided relevant information,

2. Who accompanied you during the inspection,

3. Who refused access to required records or any other 

refusal of information (Note: a separate heading for 

Refusals may be needed if refusals are significant, 

extensive or an Inspection Warrant is anticipated),

4. Who refused to permit inspection (IOM 5.2.5.1) and

5. For human drug inspection reports, also include the 

name, title, physical mailing address, phone, and fax 

number and e-mail address for any U.S. Agent or broker 

who represents the company when dealing with the 

FDA, and

6. For human and animal food program firms: Full name, 

title, and email address for the Industry Portal 

Representative (IPR). The owner, operator, or agent in 

charge (OOAC) of a facility is the IPR. The IPR is the 

person responsible for managing corrective actions to 

both written FDA-483 observations and discussed 

observations in the Corrective Action Report (CAR). 

The IPR will establish the primary enterprise account for 

access to the OCAR Industry Portal and the CAR. The 

OOAC of a firm is the IPR and may not have been 

present during an inspection, but their name, title, and 

email address must be determined during the inspection 

and entered into the Firm Details within eNSpect

Describe roles and authorities of responsible individuals, 

including the full names and titles of individuals providing 

you with information.

Describe roles, authorities and responsibilities of officials at 

headquarter or corporate organizations for this firm; 

including their names, titles and addresses.

Report the following: 

1. Who is the most responsible individual at the inspected 

firm? Who is the responsible head or designated 

correspondent? Refer to IOM 5.3.6, 5.3.6.1, and 5.3.6.2.

2. Report full names and titles of owners, partners, and 

corporate officers. Who has the duty, power and 

responsibility, and authority to prevent, detect, and 

correct violation(s), and how is this demonstrated and/or 

documented? See IOM 5.3.6.2.

3. Report the chain of command; include an organizational 

chart (create if necessary).

4. Obtain a copy of public annual report, if any.

5. List the names and titles of key operating personnel.

For NAI or VAI inspections of firms with an inspectional 

history, report changes only.

5.11.4.3.8 - FIRM'S TRAINING PROGRAM

Explain coverage of the firm’s training program as stated in 

the applicable compliance program and/or as it correlates 

to the deficiencies observed during the inspection. 

The firm's training programs are of particular significance 

where inspectional findings find people may not be 

adequately trained.

5.11.4.3.9 - MANUFACTURING/DESIGN 

OPERATIONS

1. Report only changes to the firm's general overall operations, including significant changes in equipment, 

processes, or products since the previous inspection. 

Include schematics, flow plans, photographs, formulations and diagrams, if useful.

2. List names and sources of new or unusual components 

or raw materials.

3. Report equipment considered new or unusual unless 

otherwise directed.

4. Submit pertinent formulas or batch manufacturing 

records (especially those being manufactured during 

your inspection) and processing instructions with 

labeling of suspect products.

5. Indicate which aspects of the firm’s processes or 

systems you observed versus those which the firm 

described to you.

For human and animal food inspection reports, as 

applicable, include the following: 

1. Describe the product(s) covered and include basic 

food information: finished product name, product 

description with packaging; pertinent ingredients, 

intended use and conditions of storage and 

distribution.

2. Describe the process flow (receiving through 

distribution) and a description of the process at each 

step. 

3. For full scope preventive control or HACCP 

inspections describe the results of the hazard analysis 

and the adequacy and implementation of written 

programs. 

4. Describe the firm’s general sanitation procedures.

5. Describe any coverage of additional food safety 

regulations that apply to the product(s) inspected (e.g. 

LACF, infant formula, bottled water, etc.). 

For human drug inspection reports:

This section of the EIR should be organized by system 

covered during the EI as outlined in CP 7356.002. In each 

section, include a brief summary of what you reviewed in 

order to meet the key system element outlined in the CP. 

You should add more detail for the system elements found 

to be deficient, or the subject of an FDA-483 observation.

For medical device inspection reports:

1. Describe manufacturing operations by sub system covered in your inspection (Management Controls, Design 

Controls, Production and Process Controls, Corrective 

and Preventive Action Controls, Material Controls, Facility and Equipment Controls, and 

Records/Documents/Change Controls). For ALL Level 

2, 3, and "for cause" inspections: for production and 
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process controls - indicate which production processes 

were covered/ reviewed. If a subsystem was not 

specifically covered during your EI, you do not need to 

separately describe the general operations of that 

subsystem.

2. For all inspections covering CAPA - indicate which data 

sources were available for review and which were 

actually reviewed; include a brief statement regarding 

coverage or non-coverage of applicable tracking 

requirements, MDRs, sterilization, and reports of 

corrections and removals.

3. If the Design Control system was covered, indicate the 

design project(s) covered during the inspection. Where 

design activities occur at a location other than the 

manufacturing site, list the name, address of the design 

location and responsibilities of those performing the 

design activities.

4. If applicable, identify the name and address of the 

specification developer if different from either the 

manufacturing site or where design activities occur.

5.11.4.3.10 - MANUFACTURING CODES

Describe the manufacturing coding system (lot, batch, 

product, etc.), and provide a key to interpretation of 

codes.

For medical device inspections reports: where 

appropriate, include a description of the system used to 

identify and maintain control of components during the 

manufacturing process, as well as, the codes used for 

traceability (for applicable finished devices).

5.11.4.3.11 - COMPLAINTS

Complaints include those reported to the FDA by 

consumers, health care professionals, industry, etc.; and all 

complaints received by the firm.

1. Report your review of the firm’s complaint file(s).

2. In addition, if returned goods and/or documents for 

returned goods are examined, describe findings. If not 

examined, so indicate.

3. Report your follow-up of FDA received complaints 

including complaint number and action taken by the firm. 

Correlate consumer/trade complaints, Adverse Event 

Reports, MDR's, MedWatch reports to specific 

objectionable conditions observed.

5.11.4.3.12 - RECALL PROCEDURES

Describe plans and procedures for removing products from 

marketing channels if necessary. If these procedures are in 

written SOP-type format, you may reference any copies 

obtained to aid in your explanation.

5.11.4.3.13 - OBJECTIONABLE CONDITIONS 

AND MANAGEMENT'S RESPONSE

If any observations were provided to management in writing 

(FDA 483, FDA 483a, or FDA 4056.) at the conclusion of 

the inspection list each observation and report each 

observation providing information organized under the two 

headings Supporting Evidence and Relevance, and 

Discussion with Management below.

NOTE: Observations of a verbal nature (i.e., Discussion 

Items) should be reported in sufficient detail under the 

General Discussion with Management (correlate any 

Exhibits, samples, etc. to any "verbal" observations).

5.11.4.3.13.1 - Supporting Evidence and 

Relevance

Sufficiently describe the observation as necessary to relate 

the facts as you found them.

1. Identify specific pages of exhibits and/or samples (e.g., 

procedure title, section, paragraph, sentence), labeling 

text, interstate shipping records which in your judgment 

document violations so supervisors, compliance 

officers, and other reviewers can readily evaluate your 

evidence.

2. Describe verbal statements (verbatim if possible) by firm 

officials having knowledge, duty, power, and 

responsibility to detect, prevent, or correct the apparent 

violation.

3. Identify the responsible party for each apparent violation 

(i.e., if known.)

4. Identify which team member (if applicable) was 

responsible for the observation.

5. When appropriate explain how this observation relates 

to the overall situation; i.e., impact on the product, 

batches, or lots involved, and any relationship to other 

products, processes, or other FDA 483 or FDA 4056. 

observations.

6. The duration of the problem.

5.11.4.3.13.2 - Discussion with Management 

Discussion with management:

1. Report management's response to each specific 

observation, time frames given for corrections and/or 

corrective action.

2. Report any disagreements with or refusals to correct the 

observation.

For medical device inspection reports: 

1. For each observation based on sampling of records, 

indicate which Sample Table and level of confidence 

was used and the actual number of records sampled.

2. If the number sampled is different than the actual 

number reviewed, so indicate.

5.11.4.3.14 - REFUSALS

Provide full details of all refusals of/for requested 

information, statutory information, photography, entry, etc. 
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received during the inspection, including who made the 

refusal and, if available, why the refusal was given.

In the case of drug and medical device inspections, 

similarly provide full details of all instances of delaying, 

denying, limiting, or refusing an inspection encountered 

during the inspection.

5.11.4.3.15 - GENERAL DISCUSSION WITH 

MANAGEMENT

General Discussion with Management:

1. Report the names and titles of all present, including 

those present via electronic media (describe).

2. Include the name and title to whom the FDA 483, FDA 

483a, or FDA 4056. was issued.

3. Provide additional discussion items not provided in 

writing at the conclusion of the inspection, such as: 

questionable labels, labeling and/or labeling practices, 

commercialization of products covered by IDE or IND, 

fraudulent health claims, registration/listing deviations, 

lack of approved PMA, 510(k), NDA, ANDA, etc. These 

include all verbal observations deemed not to merit 

inclusion on the FDA 483, FDA 483a, or FDA 4056. 

(IOM 5.2.3)

4. A description of each warning, recommendation, or 

suggestion given to the firm, and to whom given.

5. Management's general responses to the inspection 

and/or to groups of items listed on the report of 

observations or discussed at the conclusion of the 

inspection.

6. Report if management was informed that the 

conditions observed may, after further review by the 

Agency, be considered to be violations of the FD & C 

Act or other statutes. Legal sanctions available to FDA 

may include seizure, injunction, civil money penalties 

and prosecution. Significant deviations observed 

during a foreign inspection could result in a facility’s 

product(s) being refused or detained upon entry into 

the United States.

7. Report if management was advised that if FDA 

receives an adequate response to the FDA-483, or 

other objectionable conditions, within 15 business days 

of the end date of the inspection, it may impact FDA’s 

determination of the need for subsequent action.

8. Report all significant conversations with management 

or management representatives.

5.11.4.3.16 - ADDITIONAL INFORMATION

Report changes as appropriate.

1. Describe contractors used and for what purpose. For 

Medical Device inspection reports: also include 

names and addresses of all applicable third-party

installers or servicing organizations used by the 

manufacturer. Include their responsibilities.

2. Describe suppliers (major raw material, active 

ingredient, etc.) used and for what.

3. During inspections, when violative products imported 

into the U.S. or intended to be imported into the U.S., 

are encountered, document the product and foreign 

manufacturer in the EIR. Violative products could be

rejected APIs due to non-conformance with the USP or 

applicable compendium, foods without appropriate 

labeling, etc. Send a copy of the EIR to OEIO/DIO. See 

IOM 5.2.1 and 5.11.2. 

4. For initial inspections, verify distribution patterns for the 

firm’s products, raw materials, and components to firms 

which warehouse or further process products which may 

be subject to FDA regulations. Program divisions should 

incorporate information obtained into their Official 

Establishment Inventory improvement activities and 

complete form FDA 457, Product/Establishment 

Surveillance Report as appropriate. See IOM 8.1.5.4.

5. Report pertinent facts, which do not fit another section 

of the EIR. (For firms located in foreign countries, 

include information relative to lodging and travel; for 

domestic firms, include information relative to location of 

firm if difficult to find; etc.).

6. In accordance with IOM 5.3.4.3, if photographs are 

taken during the inspection include the statement: “The 

officially sealed original copy and unsealed working 

copy discs containing the photographs taken during the 

inspection are filed with the unlabeled exhibits and 

attachments.”

7. In accordance with IOM 5.11.5.1, if electronic records 

were received on electronic storage media during the 

inspection include the statement: “The officially sealed 

original copy [USB, CD, DVD, etc.] [and unsealed 

working copy] containing the electronic records 

provided by the firm during the inspection are filed with 

the unlabeled exhibits and attachments.”

If electronic records were received via secure 

transmissions to FDA, include the statement 

“Electronic records provided by the firm during the 

inspection were obtained via [insert description of 

secure transmission used] and true copies of these 

files were stored on FDA servers in accordance with 

record management procedures.”

The bracketed information should be edited based on 

the actual storage devices obtained and if working 

copies were created.

For human drug inspection reports - PDMA Coverage:

1. Describe what sample loss, theft, or diversion reports 

were covered during the inspection.

2. Describe the firm's sample audit and security systems, 

including a review of the firm's SOP's. Significant 

problems which may contribute to the firm's inability to 

adequately monitor sample distribution via sales 

representative, mail or common carrier should be 

addressed under objectionable conditions.

5.11.4.3.17 - SAMPLES COLLECTED

List and describe samples collected during the inspection.

5.11.4.3.18 - VOLUNTARY CORRECTIONS

1. Provide a brief description of improvements initiated by 

the firm in response to a previous inspection, report of 

observations and/or a warning letter.
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2. Report voluntary destructions, recalls, and similar 

actions since the prior inspection or during this 

inspection.

3. Report any follow-up to recalls identified during the 

inspection (may be by referencing Attachment B recall 

report).

4. Include recalls to specific objectionable conditions 

observed.

5. Provide the identity of person(s) responsible for the 

corrections.

6. Report any appropriate voluntary corrections in FACTS 

CARS. For human and animal food inspections, report 

any appropriate voluntary correction in eNSpect CAR.

5.11.4.3.19 - EXHIBITS COLLECTED

List all exhibits attached. See IOM 5.11.5, Exhibits.

Briefly, describe or title each exhibit attached and include

the number of pages for each Exhibit listing.

NOTE: For complex inspections a cross-reference from the 

FDA 483, FDA 483a, or FDA 4056. and verbal 

observations to applicable exhibits and samples can be 

useful during further review.

5.11.4.3.20 – ATTACHMENTS

List all attachments. See IOM 5.11.6, Attachments.

Briefly, describe or title each attachment and include the 

number of pages for each attachment listing in eNSpect.

After issuance do not number, alter, or label FDA 

documents and/or forms (e.g., FDA 463a, FDA 482, FDA 

483, FDA 4056).

5.11.4.3.21 - SIGNATURE

All participants will sign the final narrative portion of the EIR. 

The prescribed format is to include each person’s name

and title. Refer to current eNSpect user guide for guidance 

on electronic signatures for multiple participants. 

In some cases, electronic signature by all participants is not 

possible. An example as to how this can be accomplished 

is to forward an electronic "draft" copy of the EIR for all to 

read and approve, then followed or accompanied by the 

original signature sheet. When signed, return to the lead 

investigator for uploading into eNSpect.

In rare situations (e.g., extended leave, retirement, 

deployment) a participant may not be available to sign the 

EIR. The supervisor should state in the endorsement 

“endorser acknowledges the inability of the participant to 

sign the EIR due to unavoidable circumstances”. 

5.11.5 - EXHIBITS

Exhibits are materials collected from the firm after the FDA 

482 Notice of Inspection or FDA 482d Request for FSVP 

Records is issued and before the FDA 483, FDA 483a, or 

FDA 4056 is issued or the inspection is closed out. Collect 

only records and documents which are relevant to your 

inspectional findings or are required by the assignment or 

Compliance Program. Exhibits should contribute to the 

objective of the assignment, clarify the report, and 

document violations. Exhibits include flow plans, 

schematics, layouts, batch records and procedures, etc. 

Reference and explain exhibits in your narrative report. 

Copies of procedures, patient records, etc., that do not 

serve as evidence of a violation should not be collected 

unless you are directed to do so. 

Labeling exhibits should show the entire label and must be 

legible and easy to read. Pertinent portions of exhibits in 

foreign languages should be translated, A statement 

regarding who provided translation on the documents 

should be included in the Administrative section of the 

report.

For photographs included in the report see IOM 5.3.4.4.

Exhibits are identified and included with the final EIR. 

Electronic labeling should be used to identify exhibits 

submitted with an EIR. Identification should include at least 

the firm name, FEI Number, date(s) of the inspection, the 

initials of all FDA participants, exhibit number, and page 

number(s). See IOM 5.3.8.2. Refer to the SOP titled, 

“Using eNSpect to Create, Store, and Preserve Electronic 

Records Associated with an Establishment Inspection 

Report.” 

Exhibits do not include FDA forms, copies of assignments, 

or information obtained outside of the firm. For example, 

website downloads using a computer that is not traceable 

to the U.S. government, printed prior to the start of the 

inspection, are not exhibits. If the materials collected from 

the firm are not needed as exhibits, they should be 

destroyed in accordance with your Program Division or 

office policy.

Exhibits which include medical records obtained during an 

investigation or inspection should be handled in 

accordance with current personal privacy disclosure rules. 

Such patient records should remain intact and stored in the 

official files. When copies of these records are requested 

internal to FDA, they should be redacted by obliterating the 

patients full name (keeping first and last initial only), social 

security number, date of birth, race, personal address and 

any other personal identifiers. All external requests should 

be handled by the FOI officer. Submit at least three copies 

of new or suspect labeling or other material collected as 

exhibits for labeling purposes. See IOM 4.4.7 for 

exceptions. These should be mounted in a manner so 

complete sets are submitted that can be reviewed by 

individuals in separate offices, i.e., labels 1-10 in each of 

three sets. 
CHAPTER 5 INVESTIGATIONS OPERATIONS MANUAL 2023 

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5.11.5.1 - Electronic Records as Exhibits and 

Attachments 

Electronic records included as exhibits or attachments to 

the EIR should be stored to protect the integrity of the data. 

Refer to IOM 5.3.8.3.3.1. Electronic records should be 

protected from degradation, including preventing exposure 

of the electronic storage media to extreme temperatures 

and magnetic fields where necessary. Additional 

precautions to preserve the electronic records may be 

required, and you should be guided by your program 

division procedures for handling electronic storage media.

See IOM 5.11.5 Exhibits and 5.11.6 Attachments 

If electronic records were obtained via electronic storage 

media, do not scan and upload the FDA 525 or envelopes 

containing the USB, CD, DVD, or other storage devices 

containing electronic records to eNSpect. The actual 

records included on the storage device and uploaded into 

eNSpect are the official exhibit. The original officially sealed 

storage device and unsealed working copies should be 

included with the unlabeled hard copy exhibits and 

attachments filed in accordance with applicable 

procedures. The following statement should be included in 

section 5.11.4.3.16 - Additional Information item # 7 for 

specific details. 

For information on handling photographic storage media 

see IOM 5.3.4.3 Preparing and Maintaining Digital 

Photographs as Regulatory Evidence.

5.11.6 ATTACHMENTS

Attachments as referred to here are any material not

provided by the firm during the inspection and referred to in 

the EIR, such as assignments, Center provided protocols, 

website information printed during inspectional preparation, 

etc. Non-evidentiary material attached to the narrative 

portion of the EIR should be identified as "Attachments" 

similar to IOM 5.3.8.2. Documents attached to the EIR may 

be referred to under the attachments heading, such as a 

copy of the FDA 463a, the FDA 482, FDA 483, FDA 4056, 

etc. (in form number order); but such documents/forms may 

not be numbered, altered from their issued state, bear 

adhesive identification labels, etc. See the opening 

sentence of IOM 5.10.5. List and attach copies of 

associated reports (Recall Attachment B Report, etc.).

5.11.7 - Corrections to Endorsed 

Establishment Inspection Reports 

If your EIR requires correcting or clarification after it has 

been endorsed, an amendment may be prepared at the 

request of your supervisor. Amendments should only be 

required for significant errors or omissions, e.g. dates, 

incorrect names, lot numbers, type of operation, or 

grammatical errors that change the intended context of the 

report.

The amendment will be written using the original EIR as the 

starting document. The word “Amendment” should be 

placed after the words “Establishment Inspection Report” in 

the header. A sequence number should accompany the 

word Amendment. Example “Amendment 1”. Changes 

made to correct errors in the text of the EIR should remain 

visible; bold all additions and strike through all removals. 

The amended narrative report will be processed through 

eNSpect. 

The coversheet must be re-endorsed by the supervisor. 

At the beginning of the endorsement text, indicate that an 

amendment has been made to the report with a brief 

explanation as to why an amendment was necessary and 

if additional documents were added to the report.

SUBCHAPTER 5.12 – COMBINATION 

PRODUCTS 

5.12.1 – COMBINATION PRODUCT 

INSPECTIONS 

 

As set forth in part 3 (21 CFR part 3), a combination 

product is a product comprised of any combination of a 

drug and a device; a device and a biological product; a 

biological product and a drug; or a drug, a device, and a 

biological product (see also 2.7.1.3.7). These articles 

retain their regulatory identity when they become 

constituent parts of a combination product., Accordingly, 

the authority for inspections of combination products 

arises from the authorities for drug, device and biological 

product inspections as described in IOM 5.5, 5.6, and 5.7, 

respectively. 

All combination products are subject to at least two sets of 

CGMP requirements. In 21 CFR part 4, subpart A, section 

4.3 identifies a streamlined approach to demonstrate 

compliance with the drug CGMPs (21 CFR part 210 & 

211) and the device Quality System (QS) Regulation (21 

CFR part 820) for single-entity and co-packaged 

combination products that contain a drug or biological 

product constituent part and a device constituent part. 

This allows a combination product manufacturing facility to 

comply either with the drug CGMPs and specific called-out 

provisions from the device QS regulation (drug CGMPbased streamlined approach, see 21 CFR 4.4(b)(1)) or 

with the device QS regulation and specific provisions from 

the drug CGMPs (device QS regulation-based streamlined 

approach, see 21 CFR 4.4(b)(2)). Regardless of whether a 

streamlined approach is used, in addition, for a 

combination product that includes a biological product, the 

manufacturer must demonstrate compliance with all 

applicable CGMP requirements for biological products 

(including standards) that are found within 21 CFR Parts 

600 through 680 (21 CFR 4.3(c)). For a combination 

product that includes any HCT/P, the manufacturer must 

demonstrate compliance with all applicable regulations in 

21 CFR Part 1271. 
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5.12.1.1 – Preparation 

 

Identify the combination products manufactured at the 

facility and, if not already known, identify the lead center. 

The lead center is the medical product center (e.g., CBER, 

CDER, or CDRH) that has primary jurisdiction for a 

specific combination product’s review and regulation. 

Questions on which center is lead for a combination 

product should be directed to combination@fda.hhs.gov. 

Typically, the application type for the combination product 

is aligned with the lead center (for example, generally, 

PMA and 510(k) products are CDRH-led, and NDA/ANDA 

products are CDER-led). The lead center serves as the 

primary point of contact before, during, and after the 

inspection. For a CDER-led combination product 

inspection, review IOM 5.5. For a CDRH-led combination 

product inspection, review IOM 5.6. For CBER-led 

combination product inspection, review IOM 5.7. 

 

 

Obtain the following information before the inspection 

whenever possible: 

 

• The CGMP operating system in use at the facility. 

Although most combination product 

manufacturers choose to follow a streamlined 

approach that aligns with the lead center/ 

application type (e.g., a facility manufacturing a 

combination product approved under a PMA 

follows a device QS regulation-based streamlined 

approach), they may choose to follow either of the 

streamlined approaches or full compliance with 

both sets of regulations. 

 

• Information about the facilities involved in the 

manufacturing (including design activities) for the 

combination product and the scope of CGMP 

responsibilities of the facility to be inspected. 

 

• For pre-announced inspections, confirm that 

documentation to enable review of compliance 

with called out provisions will be available or 

accessible at the site being inspected. 

 

 

5.12.1.2 – Inspectional Approach 

 

For combination product CGMP inspections for CDER-led 

or CDRH-led single-entity or co-packaged combination 

products, follow Compliance Program 7356.000 and 

associated commodity-specific compliance programs for 

pre-approval, post approval, surveillance, for cause, and 

other risk-based inspections. For surveillance inspections 

where combination product coverage is conducted, 

prioritize combination products recently approved, cleared, 

or significantly changed (in terms of design) or those that 

include complex technology or manufacturing 

considerations. This applies unless there are indicators 

that there are safety and effectiveness concerns with other 

products. 

 

For CBER-led combination product inspections, contact 

OBPO supervisory staff and CBER for assistance. 

 

5.12.1.3 – Registration and Listing 

 

Combination products are generally registered and listed 

with the lead Center only. However, they may also be 

registered with a secondary Center. In both instances, the 

listing should reflect that the product is a combination 

product.   If potential problems related to registration and 

listing are identified, contact the lead center for 

assistance. 

 

5.12.1.4 – Combination Product 

Establishment Inspection Report 

 

A single EIR and, when applicable, FDA-483 should be 

used to document all observations made during an 

inspection at a combination product manufacturer. 

5.12.1.5 – Limitations on Inspection 

The limitations on the agency’s ability to access audit 

results (see IOM 5.6.2.2) also apply to an inspection of a 

combination product manufacturer. 
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5-1 FORM FDA 482 NOTICE OF INSPECTION
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5-2 - FORM FDA 482a
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5-3 FORM FDA 482b
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5-5 FORM FDA 483 

DEPARTMENT OF HEALTH AND HUMAN SERVICES

FOOD AND DRUG ADMINISTRATION

DISTRICT OFFICE ADDRESS AND PHONE NUMBER

Minneapolis District

250 Marquette Ave. South, Suite 600 

Minneapolis, MN 55401 

Industry information: www.fda.gov/oc/industry

DATE(S) OF INSPECTION

10/5-7/2008

FEI NUMBER

0000112233

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT IS ISSUED

TO: William S. Gundstrom, Vice President, Production

FIRM NAME

Topline Pharmaceuticals “T.L.P.”

STREET ADDRESS

2136 Elbe Place

CITY, STATE AND ZIP CODE

Jackson, MN 55326

TYPE OF ESTABLISHMENT INSPECTED

Tablet Repacker

THIS DOCUMENT LISTS OBSERVATIONS MADE BY THE FDA REPRESENTATIVE(S) DURING THE INSPECTION OF YOUR FACILITY. THEY ARE INSPECTIONAL OBSERVATIONS; AND DO NOT 

REPRESENT A FINAL AGENCY DETERMINATION REGARDING YOUR COMPLIANCE. IF YOU HAVE AN OBJECTION REGARDING AN OBSERVATION, OR HAVE IMPLEMENTED, OR PLAN TO 

IMPLEMENT CORRECTIVE ACTION IN RESPONSE TO AN OBSERVATION, YOU MAY DISCUSS THE OBJECTION OR ACTION WITH THE FDA REPRESENTATIVE(S) DURING THE INSPECTION 

OR SUBMIT THIS INFORMATION TO FDA AT THE ADDRESS ABOVE. IF YOU HAVE ANY QUESTIONS, PLEASE CONTACT FDA AT THE PHONE NUMBER AND ADDRESS ABOVE.

DURING AN INSPECTION OF YOUR FIRM (I) (WE) OBSERVED:

List your significant observations ranked in order of significance.

See IOM 5.2.3, 5.2.3.1, 5.2.3.2, and 5.2.3.3 

SEE

REVERSE

OF THIS

PAGE

EMPLOYEE(S) SIGNATURE

Sylvia H. Rogers 

EMPLOYEE(S) NAME AND TITLE (Print or Type)

Sylvia H. Rogers, Investigator

DATE ISSUED

10/7/2008

FORM FDA 483 (9/08) PREVIOUS EDITION OBSOLETE INSPECTIONAL OBSERVATIONS PAGE 1 of 1 PAGES
EXHIBIT 5-5 INVESTIGATIONS OPERATIONS MANUAL 2022

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5-5

5-6 INSERTING DIGITAL PHOTOS INTO eNSpect (RESIZE PHOTO)

Screenshot - Resizing Pictures using Windows Explorer:
EXHIBIT 5-7 INVESTIGATIONS OPERATIONS MANUAL 2022

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5-65-7 INSERTING DIGITAL PHOTOS INTO eNSpect (INSERT PHOTO)

Inserting a resized picture into Microsoft Word.
INVESTIGATIONS OPERATIONS MANUAL 2022 EXHIBIT 5-8

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5-8 INSERTING DIGITAL PHOTOS INTO eNSpect (RESIZING USING MS OFFICE PICTURE 

MANAGER)

Screenshot - Using Microsoft Office Picture Manager to Resize a picture to 800 x 600 pixels.
EXHIBIT 5-9 INVESTIGATIONS OPERATIONS MANUAL 2022

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5-9 FACTS CREATE SAMPLE ASSIGNMENT SCREEN

5-
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5-10 FORM FDA 482c NOTICE OF INSPECTION – REQUEST FOR RECORDS
EXHIBIT 5-11 INVESTIGATIONS OPERATIONS MANUAL 2022

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5-11 FOOD ADDITIVE NOMOGRAPH I
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5-11 FOOD ADDITIVE NOMOGRAPH II
EXHIBIT 5-11 INVESTIGATIONS OPERATIONS MANUAL 2023

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5-12 SUMMARY OF REGISTRATION AND LISTING HUMAN PHARMACEUTICALS

SUMMARY OF REGISTRATION AND LISTING REQUIREMENTS FOR THE MANUFACTURE OR DISTRIBUTION OF 

HUMAN PHARMACEUTICALS

TYPE OF FIRM

REGISTRATION STATUS LISTING STATUS FACTS

CODE

Manufacturer [including homeopathic & controlled drugs] yes yes M

Contract Manufacturer yes yes M

Own Label Distributor no yes L

Wholesale Distributor (no manufacturing or distribution under own 

name and label) no no W-*

Own Label Repacker yes yes R

Own Label Relabeler [including recirculizer] yes yes Y

Contract Relabeler yes yes Y

Contract Testing Laboratory [dosage forms & active ingredient 

release] yes no C

Contract Testing Lab [doing non-release tests] no no C

Contract Sub-Manufacturer yes yes M

IND Manufacturer [Clinical Drugs] no no M

NDA and ANDA Manufacturer yes yes M

Sponsor/Monitors/Clinical Investigator no no 4, 5, 6, 

7

Contract Sterilizer yes yes 0

Fulfillment Packager [adding substantive labeling] yes yes Y

Mail Order House [adding insubstantial labeling] no no D

Printing House no no None

Medical Gas Transfiller yes yes MG

First Aid/Rescue Squad [transfilling for own use] no no MG

Medical Gas Transfiller [operating out of a van] yes yes MG

Contract Assembler yes no M

Active Drug Substance Manufacturer yes yes M

Excipient Drug Manufacturer no no M

Manufacturer of Research Drugs no no M

Drug Importer no no A

Foreign Drug Manufacturer yes yes M

Methadone Clinic no no T

Retail Pharmacy no no D

Salvage Operation yes no X

Biopharmaceutical Clinical Facility no no 2

Outsourcing Facility yes no OF

*Includes W, WA, WF, WR, and/or WZ
INVESTIGATIONS OPERATIONS MANUAL 2022 EXHIBIT 5-13

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5-13 SUBSTANTIALLY EQUIVALENT MEDICAL DEVICES

Operation Submit 510(k) Register List COMPLY W/GMP

1. Manufacture and distribute device YES: 807.81(a) YES 807.20(a) YES 807.20(a) YES

2. Contract manufacturer who commercially distributes 

device for specifications developer

NO: 807.81(a) YES if domestic: 

807.20(a)(2), YES if 

foreign 807.40(a)

YES if domestic 

807.20(a)(2), YES if 

foreign 807.40(a)

YES

3a. Contract manufacturer who meets the definition of 

finished device manufacturer per 21 CFR 820.3(l).

NO YES 807.20(a)(2) YES 807.20(a)(2) YES

3b. Contract manufacturer who does not meet the 

definition of finished device manufacturer per 21 CFR 

820.3(l) (e.g., component manufacturer, subassembler) 

NO NO NO NO

4. Manufacturer modifies device or new intended use and 

distribute

NO: preamble no. 17 & 18 FR 

8/23/77 YES: 807.81(a)(3) with 

signif. change in device or use

YES 807.20(a) YES 807.20(a) YES

5. Located in US and distribute US made device. No 

specification initiation (domestic distributor)

NO: 807:85(b) NO: 510(g)(4) of act, 

807.20(c)

NO 807.20(c) NO

6. Specification initiator and distribute only YES: 807.81(a) YES: 807.20(a)(1) YES: 807.20(a)(1) YES: 820.181, etc.

7. Specification consultant only; no distribution NO NO: NO NO

8 Relabeler or repacker: change labeling or packaging in 

manner other than adding own name

YES YES: 807.20 (a)(3) YES. 807.20(a)(3) YES 820.3(w), 820.3(o) and 

Preamble Comment 28, FR 

52610

9. Relabeler or repacker: distribute under own name NO: 807.85(b): no change to 

device or existing labeling and 

another person has a cleared 

premarket notification application

NO NO NO

10. Kit assembler using prelabeled & prepackaged devices 

only

NO: no change in device or 

existing labeling other than 

adding dist. name & address 

807.81(a)(3)

YES: 807.20(a) YES: 807.20(a) YES

11. Kit assembler changes intended use (801.4) of 

prepackaged/prelabeled devices

YES: 807.81(a) YES: 807.20(a)(3) YES: 807.20(a)(3) YES: 820.120, 820.130, etc.

12. Kit assembler changes prepackaged/prelabeled 

devices

NO: if no significant change to 

labeling or device: otherwise 

YES: 807.81(a)(3)(i)

YES: 807.20(a)(3) YES: 807.20(a)(3) YES

13. Manuf. Accessory, component and package & label for 

health purpose to end user.

YES: 807.81(a) YES: 807.20(a)(6) YES: 807.20(a)(6) YES

14. Manuf. Components & dist. Only to finished device mfr. NO: 807.81(a) NO: 807.65(a) NO Use as guide: 820.1

15. Contract mfr. Of subassembly or component (see no. 

13, accessory)

NO NO NO Primary mfr. must see that 

GMP is met 21 CFR 820.50

16. Contract packager or labeler NO YES YES Yes 820.2(a)(1) 820.3(o)

17. Contract Sterilizer NO YES if domestic 

807.20(a)(2), YES if 

foreign 807.40(a)

YES if domestic 

807.20(a)(2), YES if 

foreign 807.40(a)

YES

18. Manufacture custom device (domestic or foreign) NO: 807.85(a)(1)&(2) YES 807.20(a) YES 807.20(a) YES: also see 520(b); 520(f)

19. U.S. Establishment who manufactures for export only NO YES 807.20(a) and 

807.25(g)(5)

YES 807.20(a) and 

807.25(g)(5)

YES

20. Foreign manufacturers and all foreign establishments YES: 807.81 YES, 807.40(a) YES 807.40(a) YES

21. Initial distributor/importer of device YES: 807.81(a) or 807.85(b) 

unless 510(k) has been filed by 

foreign manufacturer or another 

init. Dist

YES: 807.20(a)(5) NO:Must identify 

foreign 

manufacturer(s) or 

device(s) imported)

YES: 807.3(d), 820.198, 

820.100, 820.200, etc.

22. Installer-mfr.'s agent NO NO NO YES: 820.170

23. Installer-user NO NO NO NO: for x-ray see 1020.30(d) 

report

24. Device being investigated under ide Exempt: 812.1(a) NO NO: 807.40(c) Exempt per 812.1(a), except 

for Design Control per 

820.30

25. Mfr. Buys manufacturing rights for device (see no. 4) NO: preamble 18 FR 8-23-77 

only if same type of manuf. equip. 

is used and no signif. change to 

device

YES: 807.20(a) YES 807.40(a) YES

26. Reprocessor of single use device YES YES: 807.20(a)(4) YES: 807.20(a)(4) YES

27. Foreign exporter of device (device manufactured in 

foreign country)

YES: (original manufacturer's 

510(k) maybe used)

YES: 807.40 (a) YES: 807.40 (a) YES 820.1(a)(2) YES
EXHIBIT 5-14 INVESTIGATIONS OPERATIONS MANUAL 2022 

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5-14 eNSpect PROFILE - COMSTAT

PROFILING A FIRM’S CGMP/QS COMPLIANCE STATUS

Table 5-14.1 Quick Reference Guide

Table 5-14.2 Example of a Maintain Profiles Screen

5-14.1 Introduction

5-14.2 Purpose

5-14.3 Instructions

5-14.3.1 Pre-Inspection Preparation

5-14.3.2 Firm’s Operations

5-14.3.3 Maintain Profiles Screen

5-14.3.4 Previous Inspection Profile

5-14.3.5 Firm information

5-14.3.6 Inspection Coverage of Profile Class 

Codes

5-14.3.7 Discontinue and Delete Buttons

5-14.3.8 CGMP Inspection and Other Toggle 

Buttons

5-14.3.9 Initial, In Review, and Final

5-14.3.10 Final Profile Status 

5-14.3.10.1 Other Status

5-14.3.10.2 Acceptable Status

5-14.3.10.3 Unacceptable Status

5-14.3.11 Remark Status Field

5-14.3.12 Remarks Field

5-14.3.13 Out-of-Business Firm

5-14.3.14 Firm Merge

5-14.3.15 Troubleshooting

5-14.4 Contact Information

5-14.5 Data Quality Assurance Projects

5-14.6 Establishment Profile Criteria

Table 5-14.6.1 Device, Biologic, Drug, and 

Veterinary Establishments TO 

Profile

Table 5-14.6.2 Establishment and Operations 

NOT to Profile.

5-14.6.3 Pre-Approval Inspection 

5-14.7 Profile Classes and Codes

5-14.7.1 Profile Class Codes

Table 5-14.7.1.1 Biologics

Table 5-14.7.1.2 Devices

Table 5-14.7.1.3 Drugs and Veterinary

Table 5-14.7.1.4 Special Veterinary

Table 5-14.1 Quick Reference Guide

Review 

Status Profile Status

Data 

Entry 

Role

Remarks Field Remarks Status

Field Purpose

Initial

Further Action 

Indicated IB Review and date

Ex: “Referred to CB mm/dd/yy” EI is potentially OAI

Acceptable IB Usually no Remarks required. EI is NAI or VAI.

In 

Review Pending CB

Recommended enforcement or 

alternative action; with date as well 

as review and date.

Ex: “Recommend WL; Under 

review by [CB/Center]”

Enforcement or alternative 

action recommended.

Final

Other IB/CB

Enter the action firm is operating 

under

Ex: “Consent Decree (CD) for

CGMP (Current Good

Manufacturing

Practices)/QS (Quality Systems)

violations signed on

mm/dd/yy.” If the CD includes a

sunset clause/date, add to

Remarks.

or 

“AIP invoked on mm/dd/yy.” 

When the firm is operating 

under CD/Injunction/AIP 

(Application Integrity Policy) and 

the CGMP/QS EI is:

NAI or VAI, then “Acceptable 

(AC)”; 

or 

the inspection is OAI and 

further enforcement action is 

taken, then the Remarks Status 

is “Unacceptable (UN).”

Firm is operating under a CD or 

AIP, and a subsequent CGMP 

EI has occurred.

Enforcement Action may involve 

medically necessary products or 

be process or product specific. 

In this case, such conditions 

should be reflected in Remarks 

field (see 3.10 & 3.11(2)).

Acceptable IB/CB No outstanding OAI inspections, 

no compliance actions.

NAI and VAI inspections; or 

OAI inspections where no 

enforcement action was taken 

and/or was downgraded to VAI.

Unacceptable CB

Enter regulatory action taken and 

date.

Ex. WL issued 1/1/18. 

 UTL issued 3/10/18. 

 Reg meeting held 4/10/18.

Only after an enforcement 

action occurred as a result of a 

CGMP/QSIT EI.
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Table 5-14.2 Example of a Maintain Profiles screen

5-14.1 Introduction

Firm profiles provide a snapshot of the firm’s compliance 

status with CGMP or QS regulations. Profile status is 

monitored for domestic and foreign firms that 

manufacture, repack, label/relabel, sterilize, or test drug, 

medical device, or biological products.

5-14.2 Purpose

Firm profiles provide the compliance status as well as an 

inventory of product categories covered during a 

CGMP/QS inspection and are used to support:

• The Government Wide Quality Assurance Program 

(GWQAP). 

• External users such as state and local regulatory 

authorities and foreign government agencies.

• Other FDA operations such as drug product 

approvals, export certificates and imports.

5-14.3 Instructions

5-14.3.1 Pre-Inspection Preparation

To obtain a comprehensive history of the firm you are 

going to inspect, go to ORADSS Domestic Reports folder 

named Establishment History Report and select EHR101 

Firm Info and run the report entering the FEI you want 

reported. Make sure that a final status has been entered 

for all Profile Classes (PCs) for the previous inspection. 

If you find that one or more PCs have an initial status but 

not a final status, bring this to the attention of your 

supervisor and finalize prior entering any updates.

5-14.3.2 Firm’s Operations

For profile purposes, the firm’s operation type can be 

either as a single entity or in combination with other 

operations. Look at all the possibilities in the drop down 

menu before making a selection. Some selections allow 

for multiple operations. See below for examples: 

a. Specification Developer Only versus Specification 

Developer Also. 

When a firm is a specification developer and they do 

not manufacture any medical products onsite, select 

profile class code, SPD, and the Operation Type, 

“Specification Developer Only.”

When a firm is a specification developer and they do 

onsite manufacturing of medical products which are 

not the subject of the specifications developed, 

select SPD with the Operation Type “Specification 

Developer Also” and select the appropriate profile 

class of the products they manufacture with 

Operation Type “Manufacturer.”

b. Veterinary Drugs Also versus Veterinary Drugs Only. 

When a firm manufactures both veterinary and 

human drugs, select the appropriate profile class 

code(s) that defines its operation then select the 

Operation Type Veterinary Drugs Also. When a firm 

manufactures veterinary drugs only, select the 

appropriate profile class code(s) that defines its

operation then select the Operation Type Veterinary 

Drugs Only.

5-14.3.3 Maintain Profiles Screen

When entering profile information, it is important to 

access the Maintain Profiles screen properly as 

accessing a profile screen incorrectly will result in data 

quality errors.

The correct way for Field Offices and Centers to access

the Profile screen is to use eNSpect, accessed from the

eNSpect App link found on the Inside. FDA’s ORA

Production Applications page. From the menu toolbar,

enter the FEI or eNSpect Operation and once the

inspection record is selected, click the left-hand side Firm 

tab then select the Firm Profiling tab. You are now ready

to enter/update the profile status.

5-14.3.4 Previous Inspection Profile

It is important that the profile for the previous inspection 

be complete with a final profile status for each PC before 

updating the profile for the current inspection. If this is not 

done, a banner will appear saying “Initial data already 

exists,” and it will not be possible to close the current 

inspection in eNSpect on the Firm Profiling screen.

5-14.3.5 Firm Information

The Firm Overview, Additional Details, and the Firm 

Profiling screens should agree in firm name, address, 

and FEI number. For questions, contact the GWQAP 

staff gwqap@fda.hhs.gov.

5-14.3.6 Inspection Coverage of Profile Class 

Codes

When a CGMP/QS systems-based inspection is 

performed, coverage should reflect the overall state of 

control for the firm’s operations. For this reason, the PCs 
EXHIBIT 5-14 INVESTIGATIONS OPERATIONS MANUAL 2023

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should reflect all product classes produced by the firm as 

well as those covered during the inspection.

When a firm manufactures more than one commodity, 

e.g., drugs and devices, and the inspection covers only 

the drug systems, then only update the PCs that 

represent the drug commodity. See 5-14.7 for more 

information about profile classes and codes.

5-14.3.7 Discontinue and Delete Buttons

Proper use of the Discontinue and the Delete buttons*:

Discontinue button – The PCs should be discontinued if 

a firm goes out-of-business or no longer manufactures a 

drug, device, or biologic product.

Delete button - PCs and data entered in error can and 

should be deleted prior to clicking the save button and 

exiting the screen.

NOTE: If you save incorrect data before realizing it and 

you cannot delete it, contact the GWQAP Team for 

assistance. See 5-14.4 for Contact Information.

5-14.3.8 CGMP Inspection and Other Toggle 

Buttons

The CGMP Inspection toggle button is automatically 

activated when the Profile Required field is checked on 

the Maintain Inspection Results screen. The Other radio 

button should not be used for profiling purposes.

5-14.3.9 Initial, In Review, and Final

As reflected in Table 5-14.1 above, profile status should 

be entered as follows:

Initial: Normally entered by the Investigator. Potentially 

OAI inspections should be immediately entered as FAI 

and NAI/VAI as AC.

In Review: Pending should be entered by the 

Compliance Officer as soon as the record is received for 

review.

Final: AC should be entered by the Supervisor for 

NAI/VAI inspections; UN should be entered by the 

Compliance Officer for OAI inspections when a 

regulatory action has been taken. 

NOTE: The Status Date automatically records the date 

that the information is entered or updated in Initial, In 

Review, and Final Profile Status. It is important to 

maintain the integrity of the profile information by not 

changing this date.

Foreign firms: The Divisions enter the initial status only 

and the appropriate Center enters the final profile class 

status.

For inspections covering CDER-regulated products the 

Office of Pharmaceutical Quality Operations (OPQO) 

will be the business unit entering the profile decision 

(Initial-Final) for domestic and foreign NAI and VAI 

inspections with the exception of for-cause assignments 

issued by CDER. . 

For inspection classifications of OAI and for NAI/VAI 

for-cause assignments issued by CDER, OPQO staff 

will be entering the Initial and in-Review status and 

CDER will enter the final profile decision. 

5-14.3.10 Final Profile Status 

It is important for the Field and Centers to understand 

that final profile status should be promptly entered when 

a final agency decision has been made. Profiles should 

not be held in Pending status if the Division or Center 

decides that the course of action is to not take 

enforcement action as defined by FMD-86, and, instead, 

re-inspect.

5-14.3.10.1 Other Status

Other should be entered as the final profile status for all 

profile class codes when a firm is operating under a 

consent decree (CD) or Application Integrity Policy (AIP). 

See Tables 5-14.1 & 5-14.2 above for more information.

5-14.3.10.2 Acceptable Status

AC should be entered as the final profile status when an 

inspection is classified as NAI or VAI and the firm is not 

operating under a CD or AIP. See Table 5-14.1 above 

for more information. If an OAI is not supported by an 

enforcement action, it is entered as AC as defined in 

Field Management Directive (FMD)-86.

5-14.3.10.3 Unacceptable Status

UN should be entered as the final profile status when 

there is an outstanding OAI inspection. 

5-14.3.10.3.1 Continuation of Unacceptable 

Status

A UN status along with the regulatory action taken may 

be carried forward from one inspection to the next when 

the follow-up inspection reveals the firm had not 

addressed the violations identified in the original OAI 

inspection or an enforcement action. In this case, it is 

important that the Remarks field note this condition. See 

5-14.3.11 Remarks field for more information.

5-14.3.10.3.2 Changing from Unacceptable 

to Acceptable Status

A UN status may be changed to AC when the agency’s 

review of the firm’s response to a warning letter reveals 
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the firm’s corrective actions adequately address the 

violations identified, a re-inspection for verification may 

or may not be warranted. The Remarks field must note 

the reason for the change.

5-14.3.11 Remark Status Field

The Remark Status field is used mainly to indicate the

compliance status of a current inspection while the firm

operates under a CD or AIP. See Tables 5-14.1 & 5-14.2 

for more information and examples.

It may also be used to indicate an exception to the general 

compliance status. The profile status when under a CD will 

be “Others.” The Remarks Status Field will show the current 

compliance inspection status (AC/UN). The Remarks Field 

will note that the firm is operating under a CD (include date 

and any information required concerning the current 

inspection.

5-14.3.12 Remarks Field

The Remarks field is a narrative field that is to be used 

as often as needed to:

1. Track the status of any potential or completed 

enforcement or alternative action with dates. This 

may include an explanation for a continuation of an 

UN final profile status from one inspection to the next 

when the follow up inspection reveals the firm’s 

corrective actions were found inadequate. See Table 

5-14.1 above or 5-14.4 below for more information 

and accessing the ORA/OISM/DSS/ESB intranet 

site, respectively.

2. Indicate when a firm is operating under a CD or AIP 

with date. Note when there are specific conditions 

such as product(s) subject to the CD or AIP. This 

information must remain in Remarks for each PC 

until the CD/AIP is vacated or revoked.

3. Indicate the regulatory action and date regulatory 

action was issued.

4. Identify product(s) covered when using the catch all 

PCs MIS for devices, BMI for biologics and NEC for 

drugs; and

5. Indicate where a sterilization process(es) takes place 

such as onsite at the manufacturer, or offsite by a 

contract sterilizer. If offsite, include the name, 

address, and FEI of the contract sterilizer.

NOTE: After entering the information once, a copy and 

paste method can be used to update the Remarks field 

for each profile class involved as follows:

a. Highlight the narrative text by clicking in the Remarks 

field.

b. Select CTRL C to copy.

c. Select CTRL V to paste. 

5-14.3.13 Out-of-Business Firm 

When a profiled firm goes out of business, changes 

operations, or discontinues production of FDA regulated 

products, record the appropriate information in the 

eNSpect Application. From the Offline Field Client select 

the Firm Information tab followed by the Firm Profiling tab 

to discontinue each profile class code then select Save.

Navigate to the Assignment Details Page and select the 

Convert to Investigation followed by selecting the OOB 

(Out of Business) Washout Reason and confirm the

selection. Synchronize to upload data to eNSpect Online.

From the Online Application select the assignment and 

Navigate to the Firm Overview tab. Select the Work 

Obligation as N No from the drop-down and select the 

Save Assignment button.

Once the Investigation is complete, the Out of Business 

data will get synched with the Firm Management 

Services and will update the firm’s operational status to 

Out of Business and Work Obligation to No. 

For assistance, contact the GWQAP Team. See 5-14.4

below for contact information.

5-14.3.14 Firm Merge 

Before attempting to merge two or more firm records, 

always check to ensure all profile class codes have been 

finalized. Do not attempt to merge if the profile status is 

left in Initial or In Review. Merging firms where the profile 

classes are not finalized will cause problems that can 

only be resolved by GWQAP staff. See 5-14.4 below for 

contact information.

5-14.3.15 Troubleshooting

Troubleshooting information may be found at the 

GWQAP intranet site. See 5-14.4 for intranet site 

location.

5-14.4 Contact Information

To reach the Government Wide Quality Assurance 

Program select 

http://inside.fda.gov:9003/ORA/Offices/OPOP/ISM/DSS

/ucm557080.htm. To contact the GWQAP Team 

email

gwqap@fda.hhs.gov. 

5-14.5 Data Quality Assurance Projects

Our GWQAP stakeholders, including the Department of 

Veterans Affairs (VA), the Defense Logistics Agency 

(DLA), as well as several Local, State, and Foreign 

Governments, use an external view of eNSpect profiles

through the COMSTAT application to help them make 

procurement decisions for medical products. Since 

these stakeholders can view only the latest acceptable 

or unacceptable final profile status, profile classes must

be finalized. 
EXHIBIT 5-14 INVESTIGATIONS OPERATIONS MANUAL 2023

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Each Division and Center is responsible for management 

of firm profiles specific to it by entering profile information 

and providing a profile status as soon as a final Agency 

decision is made. The GWQAP Team in the Division of 

Systems Solution/Enforcement Systems Branch 

(DSS/ESB) is responsible for monitoring the Divisions

and Centers profile entries and communicating with the 

same on profile issues when profile information is 

incomplete, incorrect, or missing. To accomplish this, on 

a quarterly basis, an Online Reporting Analysis Decision 

Support System (ORADSS) program is run. Duplicate 

entries and non-finalized profile entries are addressed 

and a follow up is made with the Divisions and Centers 

when incomplete entries and/or errors are found. This 

data is maintained in an Excel program. It is the 

responsibility of the GWQAP Team to assure that 

eNSpect and COMSTAT views are accurate, complete, 

and current.

Accessing and Running an ORADSS Report

1. From Inside. FDA select IT Applications located 

under Services.

2. Select ORA Applications and click the ORADSS 

link.

3. Select Folders in the lower left corner.

4. Select the + Public Folders.

5. Select + Domestic Reports.

6. Select Firms.

7. Select FIR034_Profiles by Division.

8. A dialog box will appear to enter information

a. From the top of the dialog box, select 

the appropriate Home District.

b. Select GMP Insp Date (Start) by 

entering xx/xx/xxxx into the window that 

appears.

c. Select GMP Insp Date (End) by 

entering xx/xx/xxxx.

d. Select Enter to Run Query.

9. Saving the Report in Excel

a. From the toolbar, select the down arrow 

of Export.

b. Click Export Document as and select 

Excel.

c. Excel will open with the imported data.

10. Removing Duplicate Entries in eNSpect

a. Contact the GWQAP Team.

Under this procedure:

1. Profile Monitors are responsible for 

running quarterly reports from January 

1- December 31.

2. The GWQAP Team is responsible for 

conducting quarterly work group 

meetings and to follow-up with each 

Division to ensure profiles are up-todate.

5-14.6 Establishment Profile Criteria

Table 5-14.6.1 Device, Biologic, Drug, and 

Veterinary Establishments TO Profile

Manufacturer Makes a new or a changed product 

from one or more ingredients. 

Remanufacturer

Processes, conditions, renovates, 

repackages, restores, or performs any 

other act to a finished device that 

significantly changes the device's 

performance or safety specifications or 

intended use.

Reprocessor Performs remanufacturing operations 

on a single use device.

Packer/ 

Repacker

Packs a product or products into 

different containers without making any 

changes in the form of the product.

Labeler/Relabeler

An establishment which affixes the 

original labeling to a product or 

changes in any way the labeling on a 

product without affecting the product or 

its container.

Contract 

Sterilizers 

Performs sterilization or irradiation of 

products or components of products 

regulated by FDA on a contract basis. 

Control Testing 

Laboratories

Performs production quality control 

work related to products regulated by 

FDA on a contract basis.

Assemblers of 

Medical Device 

Kits

Responsible for assembling finished 

devices into medical device kits.

Specification 

Developer

Initiates or develops specifications for 

a device that is distributed under the 

establishment's own name but is 

manufactured by a second person.

HCT/P 

Establishment

Manufactures licensed/approved 

HCT/Ps that are regulated under the 

FD&C Act, PHS 351, 21 CFR 1271 

and the drug (CGMP), medical device 

(QSR) or biological product 

regulations, i.e. “351 HCT/Ps”

Table 5-14.6.2 Establishment and Operations NOT 

to Profile

Blood Banks 

Methadone Clinics 

Manufacturers of "Research Use Only" Products 

Pharmacies (including pharmacy compounders) and 

Retail firms

Distributors 

Plasmapheresis Centers 

Custom Device Manufacturers 

Veterinary Medical Device Firms 

X-ray Assemblers 

Mammography Clinics 

Manufacturers of General Purpose Articles 

(Devices) 

Physicians Offices, Hospitals and Clinics 

Laser Light Shows/Television and Microwave Oven 

Manufacturers 

Sun tanning Establishments 

Device Component Manufacturers 

Clinical Investigators/Bioresearch Monitoring 

Any Non-GMP Inspection
INVESTIGATIONS OPERATIONS MANUAL 2023 EXHIBIT 5-14

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HCT/P establishments that manufacture products 

regulated solely under PHS 361 and 21 CFR 1271, i.e. 

“361 HCT/Ps”

HCT/P establishments that manufacture 

unlicensed/unapproved products that are regulated under 

the FD&C Act, PHS 351, 21 CFR 1271 and the drug 

(CGMP), medical device (QSR) or biological product 

regulations, i.e. “351 HCT/Ps”

5-14.6.3 Pre-Approval Inspections 

Pharma product specific Pre-Approval and Post 

Approval Inspections, should not be profiled unless the

inspection is the initial inspection of a new profile class 

and the inspection results in an approval 

recommendation (VAI or NAI). Withhold 

recommendations for initial profile classes (the EI is 

classified as OAI) are not profiled, this assures the 

product cannot be marketed in the U.S. until a follow-up 

inspection verifies implementation of appropriate 

corrective actions or until corrections are substantially 

verified through other appropriate means. 

Device Pre-Approval (PMA) inspections that cover the 

firm’s systems should be treated like any other QS 

inspection. In all cases the initial profile status should be 

entered by the Investigator. 

5-14.7 Profile Classes and Codes

The profile system is based upon product categories or 

classes and is not product specific. Select the most 

appropriate profile class(es) to describe the product(s) 

the firm manufactures or otherwise processes.

When describing devices, often more than one class is 

needed to describe the operations/assembly involved in 

the device. A rule of thumb is to think of the composition 

of the device and then select the profile classes that 

define the make-up of that device and its assembly. For 

example, a catheter and needle unit is profiled as MTL 

(metal fabrication and assembly) and PRF (plastic or 

rubber fabrication and assembly). A Cutter, orthopedic 

cast, 110 volt AC-DC, is profiled as MTL , PRF and ELE 

(electrical) For devices that have software and are 

operated by computer, codes COS (software) and COH 

(computer hardware) should be added.

SPD (specification developer) should be used if a firm 

only develops the design and specifications and has the 

device manufactured by someone else. Do not include 

other profile classes unless the firm also manufactures 

other medical products on-site. 

When describing combination product (see IOM 5.12.1) 

multiple profile codes may be needed. (e.g. for a 

combination product CGMP inspection of a facility 

manufacturing a sterile- filled prefill syringe, use profile 

codes SVS-Sterile-filled small valume parenteral drugs 

and IDD-injectable delivery device (syringes, auto 

injectors/pens)).

Catch-all codes: MIS for devices, NEC and CRU for 

drugs, and BMI for biologics can be used when product 

does not fit into any product class identified by the list of 

PCs. When using these codes, identify the type of 

product in the Remarks field for that code. If the product 

is a sterile product, don’t forget to include the appropriate 

sterilization.

5-14.7.1 Profile Class Codes

For more information, contact your Division Profile 

Monitor or the GWQAP team. See 5-14.4 for contact 

information.

Table 5-14.7.1.1 Biologics

BIOLOGICS

Profile 

Class 

Code

Definitions

AEV ANTITOXINS AND ANTIVENINS

AFP ANIMAL DERIVED FRACTIONATION 

PRODUCTS

ALP ALLERGENIC PRODUCTS

BBP BLOOD AND BLOOD PRODUCTS 

UNLICENSED

BGR BLOOD GROUPING REAGENTS

BMI

BIOLOGICAL PRODUCTS NOT OTHERWISE 

CLASSIFIED (Blood collection bags with anticoagulant, plasma volume expanders, Limulus 

Amebocyte Lysate (LAL) test kit, etc.; Note 

specific product(s) in Remarks field)

CBS COMPUTER BIOLOGICAL SOFTWARE

CGT CELL AND GENE THERAPY PRODUCTS

HFP HUMAN DERIVED FRACTIONATION 

PRODUCTS

LBI LABORATORY, BIOLOGICAL TESTING

RBD RECOMBINANT ANALOGUES OF BLOOD 

DERIVATIVE PRODUCTS

TIS HUMAN TISSUE REGULATED BY FDA

VBP VACCINE BULK PRODUCT

VFP VACCINE FINISHED PRODUCT

VIV IN VIVO DIAGNOSTICS

VTK VIRAL MARKER TEST KIT

Table 5-14.7.1.2 Devices

DEVICES

Profile 

Class 

Code

Definitions

AMP

ADDITIVE MANUFACTURING PROCESS 

(incl. 3D printing, additive manufacturing 

medical products)

CCR CLINICAL CHEMISTRY REAGENTS (including 

diagnostic tapes, sticks, etc.)

COH COMPUTER HARDWARE

COS COMPUTER SOFTWARE (Devices only)

CSP CHEMICAL STERILIZATION

CTD

CONTROL TESTING LABORATORIES "ALSO" 

(Device manufacturer that is also a contract 

testing 
EXHIBIT 5-14 INVESTIGATIONS OPERATIONS MANUAL 2023 

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lab.) 

DKA DEVICE KIT ASSEMBLER (Ex: lumbar puncture 

kit, anesthesiology kit, suture removal kit)

ELE ELECTRICAL ASSEMBLY

FSP FILTRATION STERILIZATION

GLA GLASS OR CERAMIC FABRICATION AND 

ASSEMBLY

GSP GAS (ETO, PROPYLENE OXIDE 

STERILIZATION )

HCP HEMATOLOGY AND COAGULATION 

PRODUCTS

HSP DRY HEAT STERILIZATION

HTD HUMAN TISSUE DEVICES

IDD INJECTABLE DELIVERY DEVICE (syringes, 

auto injectors/pens)

MED

MEDIA (including microbiological and tissue 

culture, growth media and accessories, and 

ingredients)

MIS NOT ELSEWHERE CLASSIFIED (Note specific 

product(s) in Remarks field)

MSO METERED SPRAY OTHER (incl. nasal 

sprays, sublingual sprays)

MTL METAL FABRICATION AND ASSEMBLY

OID ORALLY INHALED DELIVERY (incl.

MDIs, DPIs, sprays)

OPT

OPTIC FABRICATION AND ASSEMBLY (Optical 

products or parts, e.g., eye glass lenses, 

intraocular lenses, contact lenses, lens portion of 

a laser, etc.)

PAT PATCH (incl. conventional patches, micro 

needles)

PBM PROCESSED BIOLOGIC MATERIAL (Only 

animal or plant material used as a device)

PRF PLASTIC OR RUBBER FABRICATION AND 

ASSEMBLY

RIP RADIOIMMUNOASSAY PRODUCTS

RSP RADIATION STERILIZATION

SIP

SEROLOGICAL AND IMMUNOLOGICAL 

PRODUCTS (Including bacterial typing, 

rheumatoid factors, pregnancy kits, IVD other 

than VIRAL marker test kits, etc.)

SOL

DEVICE SOLUTIONS AND GELS (Including 

contact gels, dialysis solutions, dental pastes, 

adhesives, etc.)

SPD SPECIFICATION DEVELOPERS (Note in 

Remarks field where finished product

testing is conducted.)

SSP STEAM STERILIZATION

TSP FRACTIONAL TYNDALLIZATION 

STERILIZATION

TXT TEXTILE FABRICATION AND ASSEMBLY

WOD WOOD FABRICATION AND ASSEMBLY

WSP WATER STERILIZATION

Table 5-14.7.1.3 Drugs and Veterinary

DRUGS

Profile 

Class 

Code

Definitions

ADM AEROSOL DISPENSED MEDICATION

AMT

ADVANCED MANUFACTURING 

TECHNOLOGIES (including 3D printing, 

continuous drug manufacturing)

CBI RECOMBINANT/NON-RECOMBINANT 

PROTEIN DS OF BIOLOGIC ORIGIN

CEX STARTING/INTERMEDIATE DERIVED FROM 

PLANT/ANIMAL EXTRACTION

CFN NON-STERILE API BY FERMENTATION 

CFS STERILE API BY FERMENTATION 

CHG CAPSULES, PROMPT RELEASE

CRF DRUG SUBSTANCE INTERMEDIATE 

(FERMENTATION)

CRU DRUG SUBSTANCE INTERMEDIATE 

(CHEMICAL SYNTHESIS)

CRX STERILE STARTING/INTERMEDIATE/NEC (not 

Plant/Animal)

CSG CAPSULES, SOFT GELATIN

CSN NON-STERILE API BY CHEMICAL SYNTHESIS

CSS STERILE API BY CHEMICAL SYNTHESIS

CTR CAPSULES, MODIFIED RELEASE

CXA PURIFIED API DERIVED FROMPLANT/ANIMAL 

EXTRACTION

EXC EXCIPIENT (also referred to as inactive 

ingredient)

GAS MEDICAL GAS (includes liquid oxygen)

HMA HOMEOPATHIC API/drug substance/tinctures

HMF HOMEOPATHIC FINISHED DRUG PRODUCTS

LCP LABORATORY, CHEMICAL/physical testing

LIQ NON-STERILE LIQUID (other than suspensions & 

emulsions)

LMN LABORATORY, MICROBIOLOGICAL-non-sterility 

testing

LMS LABORATORY, MICROBIOLOGICAL-sterility 

testing

LVP LARGE VOLUME PARENTERALS

PTC PATCH (incl. conventional patches, no micro 

needles)

NEC NOT ELSEWHERE CLASSIFIED FINISHED 

DRUG 

OIN OINTMENT, NON-STERILE (includes cream, 

jelly, paste)

PET POSITRON EMISSION TOMOGRAPHY 

POW NON-STERILE POWDERS (Includes oral and 

topical)

SES SUSPENSIONS AND EMULSIONS (NONSTERILE)

SLQ STERILE LIQUID (other than suspensions & 

emulsions)

SON STERILE OINTMENT

SPW STERILE POWDER

SSE STERILE SUSPENSIONS AND EMULSIONS 

(NON PARENTERALS)

SUP SUPPOSITORIES

SVL SMALL VOLUME PARENTERALS (Lyophilized)

SVS STERILE-FILLED SMALL VOLUME 

PARENTERAL DRUGS

SVT TERMINALLY STERILIZED SMALL VOLUME 

PARENTERALS

TCM TABLETS, PROMPT RELEASE

TCT TABLETS, DELAYED RELEASE

TDP TRANSDERMAL PATCHES

TTR TABLETS, EXTENDED RELEASE

NOTE: API - Active Pharmaceutical Ingredient is 

sometimes referred to as Drug Substance.
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Table 5-14.7.1.4 Special Veterinary

Profile 

Class 

Code

Definitions

IMN IMPLANT NON-STERILE

IMS IMPLANT STERILE

TAM TYPE A MEDICATED ARTICLE
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5-15 COMPLIANCE ACHIEVEMENT REPORT
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5-16 FACTS REIMBURSABLE CHECK BOX 

Screenshot showing location of Reimbursable check box:
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5-17 FORM FDA 4056 - PRODUCE FARM INSPECTION OBSERVATIONS
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5-18 – FORM FDA 483a
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