1 

 

COMPLIANCE PROGRAM GUIDANCE MANUAL

 

Imported CBER-Regulated Products 

7342.007 

[See 7342.007 Addendum for Imported Human Cells, Tissues, and Cellular 

and Tissue-based Products]

 

Implementation 

Date:

 Major Update due to Automated Commercial 

Environment/International Trade Data System (ACE/ITDS) 

implementation 

October 1, 2018 

Completion 

Date:

 October 1, 2022 

Product Codes:

Product Codes with associated Agency Processing Codes and corresponding 

Commodity Subtypes and Examples 

Government Agency Program Code & Commodity: BIO - Biologics

Product Codes Agency Processing 

Codes & 

Corresponding 

Commodity Subtypes

Examples of CBER Regulated 

Products 

57A BDP

Blood Derivatives 

Antitoxins (e.g., Botulism 

Antitoxin) and Antivenins (e.g., 

snake, scorpion, spider)

57B VAC

Vaccines

Immunization Toxoids (e.g., 

Diphtheria Toxoid, Tetanus 

Toxoid)
2 

Product Codes with associated Agency Processing Codes and corresponding 

Commodity Subtypes and Examples 

Government Agency Program Code & Commodity: BIO - Biologics

Product Codes Agency Processing 

Codes & 

Corresponding 

Commodity Subtypes

Examples of CBER Regulated 

Products 

57C VAC

Vaccines

Viral Vaccines (e.g., Rabies, 

Yellow Fever, Small Pox, 

Influenza Vaccines)

57D BLO

Blood & Blood 

Products 

Blood & Blood Components, 

single donor & pheresis (e.g., 

Whole Blood (Human), Red 

Blood Cells (Human), Source 

Plasma (Human))

57E ALG

Allergenics

In-Vivo Diagnostic Products 

(e.g., Tuberculin PPD (skin test)) 

57G ALG

Allergenics

Allergenic Products (e.g., 

Allergenic Extracts, animal 

allergens, venoms (bee, wasp, 

hornet, yellow jacket))

57H VAC

Vaccines

Bacterial Vaccines/Antigens 

(e.g., Pneumococcal Vaccine, 

Meningococcal Polysaccharide 

Vaccine, Bacterial Antigen (No 

U.S. Standard Potency)

57I VAC

Vaccines

Multiple Vaccine/Multiple 

Antigen Preparations (e.g., 

Measles, Mumps, Rubella 

Vaccine; Diphtheria, Tetanus, 

and Pertussis Vaccine)

57M CGT

Cell & Gene Therapy

Umbilical cord blood stem cells, 

peripheral blood stem cells, 

Lymphocytes (Donor

Lymphocytes for Infusion, T 

Cells)

57N CGT

Cell & Gene Therapy

Cell Therapies, Gene Therapies 

(vectors, genetically modified 

cells)
3

Product Codes with associated Agency Processing Codes and corresponding 

Commodity Subtypes and Examples

Government Agency Program Code & Commodity: BIO - Biologics

Product Codes Agency Processing 

Codes & 

Corresponding 

Commodity Subtypes

Examples of CBER Regulated 

Products

57U BDP

Blood Derivatives

Blood Derivatives (e.g., 

Albumin, Immune Globulin, 

Factor XIII Concentrate, Fibrin 

Sealant))

57V BLD

Licensed Devices 

In-Vitro Diagnostic Products 

(e.g., Hepatitis B Surface 

Antigen and Human 

Immunodeficiency Virus types 1 

& 2, Reagent Red Blood Cells, 

Blood Grouping Reagents)

57W VAC

Vaccines

Immunomodulators (e.g., 

Whipworm, Hookworm)

57Y PVE

Plasma Volume 

Expanders

Plasma Volume Expanders (e.g., 

Dextran),

57Y BBA

Blood Bag with

Anti-coagulant

Biological In-Vivo and In-Vitro 

Diagnostic Products Not 

Elsewhere Classified (N.E.C.)

Program/Assignment Codes: 42007 (Imported CBER-Regulated Products)

FIELD REPORTING REQUIREMENTS

All CBER import resources are planned under 42007. Report accomplishments under 

appropriate PAC. Planned resources cover: PAC 42R833(OASIS ELECTRONIC 

ENTRY REVIEW – BIOLOGICS), 41R824/42R824/45R824 (Follow-Up to Refused 

Import Entries), 99R833 (Import Filer Evaluations) under PAC 42007.
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Table of Contents

PART I - BACKGROUND ................................................................................................ 5

PART II - IMPLEMENTATION........................................................................................ 5

A. Objectives............................................................................................................. 5

B. Program Management Instructions...................................................................... 6

PART III- INSPECTIONAL .............................................................................................. 8

A. Entry Review under Section 801 of the FD&C Act............................................. 8

B. Documents That May Be Requested.................................................................. 20

C. Special Circumstances........................................................................................ 21

PART IV - ANALYTICAL.............................................................................................. 22

PART V - REGULATORY/ADMINISTRATIVE STRATEGY..................................... 23

A. CHARGES ......................................................................................................... 23

B. ACTIONS........................................................................................................... 27

PART VI - REFERENCES/PROGRAM CONTACTS.................................................... 28

A. References.......................................................................................................... 29

B. Program Contacts............................................................................................... 29

PART VII - CENTER RESPONSIBILITY/PROGRAM EVALUATION...................... 29

Attachment A: Explanation of Terms Used in This Program........................................... 30
5

PART I - BACKGROUND

The Center for Biologics Evaluation and Research (CBER) regulates biological products, 

as well as certain drugs and devices. Current authority for this responsibility rests in the 

Public Health Service (PHS) Act and/or the Federal Food, Drug, and Cosmetic (FD&C)

Act.

CBER is responsible for ensuring:

• the safety of this nation's entire blood supply and the products derived from it; 

• the production and approval of safe and effective vaccines, including childhood 

vaccines; 

• an adequate and safe supply of allergenic products; 

• the safety and efficacy of cellular and gene therapy products; 

• the safety and efficacy of certain drugs and medical devices used in the testing and 

manufacture of biological products. 

• the safety and efficacy of certain of Human Cells, Tissues and Cellular and Tissuebased products. 

Table of Contents

PART II - IMPLEMENTATION

This program provides information to assist FDA import entry reviewers and compliance 

officers in making admissibility decisions regarding all imported biological products, 

drugs, and devices regulated by CBER under section 351 of the PHS Act and/or under the 

FD&C Act.

A. Objectives

This is a continuing program to:

1. Determine if imported biological products, drugs, and devices regulated by CBER 

comply with the requirements of the FD&C Act, the PHS Act, and the regulations 

promulgated under these statutes. Including, but not limited to:

a. Determine if finished biological products, drugs, and devices regulated by 

CBER, including blood or blood components intended for transfusion, are the 

subject of an approved BLA, NDA, ANDA, PMA, a cleared 510(k), or an 

active IND or IDE and are adequately labeled. Determine if unfinished 

biological products, drugs, and devices regulated by CBER and intended for 

further processing or manufacture and distribution in the U.S. are the subject 
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of an approved BLA, NDA, ANDA, PMA; a cleared 510(k); an active IND or 

IDE; or an FDA-approved short supply agreement, as appropriate, and are 

adequately labeled.

b. Determine if blood, blood components, Source Plasma, Source Leukocytes, or 

any component thereof that is declared as import-for-export has been 

approved by CBER for importation as required by Section 801(d)(4) of the 

FD&C Act and is adequately labeled.

c. Determine if biological products, drugs, and devices regulated by CBER that 

are declared as import-for-export comply with Section 801(d)(3) of the FD&C 

Act and are adequately labeled.

2. Detain and/or refuse entry of imported biological products, drugs, and devices 

regulated by CBER that do not appear to comply with the applicable laws.

Administratively destroy any refused drugs regulated by CBER that are valued at 

$2500 or less (or such higher amount that the Secretary of the Treasury may set 

by regulation) (21 CFR 1.94). 

B. Program Management Instructions

1. Articles/Products Covered By This Program

The Center for Biologics Evaluation and Research (CBER) is the lead center for 

regulating biological products along with certain drugs and devices. CBER has 

regulatory oversight over products belonging to the following classes:

• Antitoxins (e.g., botulism antitoxin) and Antivenins - products used in 

the treatment of venomous bites or stings (e.g., snake antivenins, 

spider antivenins) and antitoxins (e.g., botulism antitoxin); [BDP]

• Vaccines -- products intended to induce or increase an antigen specific 

immune response for prophylactic or therapeutic immunization, 

regardless of the composition or method of manufacture (e.g., 

Influenza Virus Vaccine, Polio Virus Vaccine, Diphtheria and Tetanus 

Toxoids and Acellular Pertussis Vaccine (DTaP)); [VAC]

• Blood and blood components, including Source Plasma and Source 

Leukocytes; [BLO]

• Plasma derived products (e.g., albumin, immunoglobulins, clotting 

factors, fibrin sealants, proteinase inhibitors), including recombinant 

and transgenic versions of plasma derivatives (e.g., clotting factors, 

blood substitutes); [BDP], [PVE]

• Blood bags with anti-coagulant (approved under NDA); [BBA]

• Certain devices involved in the collection, processing, testing, 

manufacture and administration of licensed blood, blood components, 
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and human cells, tissues, and cellular and tissue-based products 

(HCT/Ps) (e.g., blood bank reagents; viral marker test kits; red cell 

reagents; [BLD] 

• HIV Test Kits used to screen donors; [BLD]

• Allergenic products, including diagnostic patch tests applied to the 

surface of the skin and used by physicians to determine the specific 

causes of contact dermatitis; and allergenic extracts - injectable 

products manufactured from natural substances known to elicit allergic 

reactions in susceptible individuals and used for the diagnosis and 

treatment of allergic diseases (e.g., allergic rhinitis ("hay fever"), food 

allergy); [ALG] and 

• Human cell therapy are products that FDA has determined do not meet

all of the criteria in 21 CFR 1271.10(a) and are regulated as drugs 

and/or biological products. Cellular immunotherapies, cancer 

vaccines, and other types of both autologous and allogenic cells for 

certain therapeutic indications, including hematopoietic stem cells 

derived from peripheral and cord blood fall under this category. 

Products that introduce genetic material into a person’s DNA to 

replace faulty or missing genetic material, thus treating a disease or 

abnormal medical condition also fall in this category; [CGT]

Examples include: 

 Autologous cultured chondrocytes 

 Autologous cellular immunotherapy

 Gene therapy products

This program does NOT cover human cells, tissues, and cellular and tissue-based 

products (HCT/Ps) that are regulated solely under section 361 of the PHS Act. 

These "361 HCT/Ps" are covered under the Addendum to this Compliance 

Program [XEN, HCT]

(see

https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceR

egulatoryInformation/ComplianceActivities/Enforcement/CompliancePrograms/U

CM095253.pdf))

This program also does NOT cover the therapeutic biological products that were 

regulated by CBER but were transferred on June 30, 2003 to the Center for Drug 

Evaluation and Research (CDER). 

A complete list of the therapeutic biological products that were transferred to 

CDER can be found at 

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelope
8

dandApproved/ApprovalApplications/TherapeuticBiologicApplications/default.ht

m.

2. Import Sample Collections

If an import division decides that obtaining a sample is appropriate, that division 

should contact CBER, Office of Compliance and Biologics Quality (OCBQ), 

Division of Case Management (DCM) prior to initiating collection of the sample.

(See Part VI.B. for program contact information).

3. Field Exams

Field exams are performed, as appropriate, in accordance with established 

procedures. See IOM 6.4.6, "Field Examinations-Biologics."

Table of Contents

PART III- INSPECTIONAL

A. Entry Review under Section 801 of the FD&C Act

As of July 23, 2016, the Automated Commercial Environment/International Trade 

Data System (ACE/ITDS) became the electronic data interchange system authorized 

by U.S. Customs and Border Protection (CBP) for processing of FDA-regulated 

imports in the United States. FDA issued a final rule on November 29, 2016, which 

became effective on December 29, 2016 (81 FR 85854). This rule established 

requirements for certain key data to be submitted, at the time of entry, as part of the 

electronic import entry in ACE. 

When filing an entry in ACE, the filer must submit the following information (21 

CFR 1.72):

(a) Product identifying information for the article. This consists of:

a. FDA Country of Production

b. Complete FDA Product Code

c. Full Intended Use Code

(b) Importer of record contact information, which is the telephone and email 

address of the importer of record.

FDA Supplemental Guidance for ACE/ITDS, available on the CBP website or from this 

FDA website link, provides details on the submission of data for articles regulated by 

each Center (see 
9

https://www.fda.gov/forindustry/importprogram/entryprocess/importsystems/ucm4

56276.htm.

Intended Use Codes

Intended Use Codes (IUC) provide a consistent, systematic approach to collection of 

certain intended use information about articles being imported or offered for import 

into the United States. The regulations at 21 CFR 1.72(a)(3) require that a full IUC 

be submitted in ACE at the time of entry for each FDA-regulated article that is being 

imported or offered for import into the United States. 

1. Affirmation of Compliance

An entry reviewer should consider whether the product appears to be licensed,

approved, or cleared by CBER or otherwise subject to regulation by CBER as a 

biological product, a drug, and/or a device.

FDA uses Affirmation of Compliance (AofC) codes for filers to provide FDA 

employees with information concerning the article offered for import. The 

submission of AofC codes and/or associated data assists FDA in making 

admissibility determinations. For certain AofC codes, the filer affirms that the 

product identified in a FDA line meets FDA requirements for importation of that 

article. Other AofC codes require certain data (qualifiers) to be submitted with 

the code. Submission of the AofC code and/or data (qualifiers) was voluntary in

the CBP’s previous Automated Commercial System (ACS). However, with the 

implementation of ACE/ITDS and the final rule (21 CFR 1.72, and 21 CFR 1.78),

FDA requires submission of certain data elements (including AofC) for import of 

CBER-regulated products. When the AofC code is provided, the entry reviewer 

should verify that the code and the data (qualifiers) are accurate. for that article.

Center Views is available on FDA's Intranet through ORA's Production 

Applications page, which should enable entry reviewers to verify AofC codes. To 

access the appropriate fields (e.g., "application number," "firm license number"), 

the entry reviewers should select the "CBER" tab once in Center Views. Contact 

CBER, OCBQ, DCM (see Part VI.B. for program contact information) if Center 

Views is not operational, or if there are questions about verifying the AofC codes.

a. Licensed Biological Products

"Biological products" are defined in section 351(i) of PHS Act as “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.”

Pursuant to Section 351(a) of the PHS Act, a biologics license must be in 
10

effect for any biological product to be introduced or delivered for introduction 

into interstate commerce (including imports).

The Submission Tracking Number (STN) and/or the Biologics License 

Number (BLN) AofC codes are required for licensed biological products (21 

CFR 1.78 (c)). This information is transmitted to FDA using the following 

AofC Codes:))

• "STN" Submission Tracking Number

The Affirmation Code is "STN"; the qualifier should be the submission 

tracking number issued by FDA for the licensed biological product 

identified in the FDA line. The submission tracking number is the six digit 

biologics license application (BLA) number.

• "BLN" Biologics License Number

The Affirmation Code is "BLN"; the qualifier should be the four digit U.S. 

Biologics License Number issued by FDA to the manufacturer of the 

biological product identified in the FDA line. The biologics license 

number is the U.S. license number (not the STN number).

b. Drug Products

The FD&C Act section 201(g) defines "drug" to mean "(A) articles 

recognized in the official United States Pharmacopeia, official Homeopathic 

Pharmacopeia of the United States, or official National Formulary, or any 

supplement to any of them; and (B) articles intended for use in the diagnosis, 

cure, mitigation, treatment, or prevention of disease in man or other animals; 

and (C) articles (other than food) intended to affect the structure or any 

function of the body of man or other animals; and (D) articles intended for use 

as a component of any articles specified in clause (A), (B), or (C)." Drug 

products, with the exception of biological products that have a BLA in effect, 

must have an approved application under section 505 of the FD&C Act.

Depending on the type of application (i.e., investigational new drug, new 

drug, abbreviated new drug, the following AofC codes may be applicable:

• IND Investigational New Drug Application Number (21CFR 1.78 (f))

This affirmation and qualifier should be the Investigational New Drug 

Application Number issued by FDA (CDER, CBER) for the product 

identified in the FDA line. Investigational drugs are new drugs intended 

solely for investigational use by experts qualified by scientific training and 

experience to investigate the safety and effectiveness of drugs.

• DA is the new AofC that applies to both the New Drug Application and 

Abbreviated New Drug Application Number (NDA and ANDA) (21CFR 

1.78 (e)). 

 For NDAs regulated by CBER, DA AofC followed by the 

prefix BN and qualifier refers to the New Drug Application 

Number issued by FDA (CDER/CBER) for the product 
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identified in the FDA line. A drug may be "new" if (1) it 

contains a newly developed chemical; (2) it contains a 

chemical or substance not previously used in medicine; (3) the 

drug has previously been used in medicine but not in the 

dosages or conditions for which the sponsor now recommends 

its use; or (4) the drug has become recognized by qualified 

experts as safe and effective for its intended uses as a result of 

investigational studies but has not otherwise been used to a 

material extent or for a material time. A new drug cannot be 

commercially marketed in the U.S. unless it has been approved 

as safe and effective by the FDA based on a New Drug 

Application. The qualifier required is the NDA number 

assigned to the product by FDA (21 CFR 1.74).

 For ANDAs regulated by CBER, DA followed by the prefix

BA and qualifier refers to the Abbreviated New Drug 

Application Number (ANDA) issued by FDA (CDER/CBER) 

for the human drug product identified in the FDA line. This 

number is the approval number in response to an abbreviated 

new drug application (21 CFR 1.74).

o REG AofC followed by the Drug Registration Number is required for 

importation of NDAs and ANDAs (21CFR 1.78 (d)).

A list of currently approved new drug applications for drug products regulated 

by CBER can be located at 

http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts

/ApprovedProducts/NewDrugApplicationsNDAs/UCM149972.pdf .

c. Device Products

The FD&C Act section 201(h) defines "device" as "an instrument, apparatus, 

implement, machine, contrivance, implant, in vitro reagent, or other similar or 

related article, including any component, part, or accessory, which is (1) 

recognized in the official National Formulary, or the United States 

Pharmacopeia, or any supplement to them, (2) intended for use in the 

diagnosis of disease or other conditions, or in the cure, mitigation, treatment, 

or prevention of disease, in man or other animals, or (3) intended to affect the 

structure or any function of the body of man or other animals, and which does 

not achieve its primary intended purposes through chemical action within or 

on the body of man or other animals and which is not dependent upon being 

metabolized for the achievement of its primary intended purposes." CBER 

regulates the medical devices involved in the collection, processing, testing, 

manufacture and administration of licensed blood, blood components and 

cellular products. CBER also regulates all HIV test kits used both to screen 

donor blood, blood components and cellular products, and to diagnose, treat 

and monitor persons with HIV and AIDS.
12

In the ACE/ITDS environment there has been a major change in the 

processing of CBER regulated device imports. Licensed devices will 

continue to come under the Biologics Industry Code, but the Investigational 

Devices (IDEs) and devices regulated under PMA and 510k have been 

removed from the Biologics Commodity data section, and will now come 

under the Medical Device Industry Codes and processed under the Center 

for Devices and Radiological Health (CDRH) import processes. PM# is the 

new Affirmation of Compliance Code for the unlicensed devices (PMAs 

and PMNs). 

The processing of the CBER regulated devices is outlined below. 

Licensed Devices: 

Licensed devices should be transmitted to FDA under the Biologics 

Industry Code (BIO) and therefore should be reviewed in accordance with 

the CBER Regulated Biological and Drug Products Job Aid. Licensed 

devices have an approved BLA, and therefore the Affirmations AofC codes 

STN and BLN will apply (21CFR 1.78 (c)). 

Clinical investigations of these products are conducted under an 

Investigational New Drug Application, and therefore the AofC code IND will 

apply to these devices at the time of import. 

Investigational Devices: 

Devices that qualified experts use on human subjects, to conduct 

investigations of their safety and effectiveness, are considered investigational 

devices. The affirmation and qualifier should be the Investigational Device 

Exemption (IDE) Number issued by FDA (CDRH/CBER) for the product 

identified in the FDA line (21CFR 1.78 (h)). 

In the ACE/ITDS environment, all investigational devices will be submitted 

using the Device Industry codes. IDEs from the two Centers can be 

differentiated by the prefix G in the qualifier, which is specific for CDRH 

regulated devices. The investigational devices submitted using the Device 

Industry code without the G prefix in the qualifier would be routed through 

the CBER validation process. 

IDE Affirmation of Compliance should be followed by the Investigational 

Device Exemption Number, or the NSR qualifier to indicate that the device is 

destined for non-significant risk study.

If the NSR qualifier is used with the IDE, an Institutional Review Board 

(IRB) affirming NSR must be provided to FDA. 

Devices:
13

Device products, must have an approved premarket application (PMA), a

cleared 510(k) or a humanitarian device exemption (HDE) (21 CFR 1.78 (i)) 

and should be reviewed in accordance with the CDRH Medical Device Initial 

Admissibility Job Aid.

See Section VI.A, references 9 and 10, for links to lists of approved and 

cleared device products regulated by CBER.

PM# is the Affirmation AofC Code for both PMA-approved and 510(k) 

cleared devices. This affirmation and the qualifier for this code should be 

the Device Premarket Approval Number or the Device Premarket 

Notification (510(k))/De-Novo Number issued by FDA/CBER for the 

product identified in the FDA line. Humanitarian Device Exemption (HDE) 

will also come under the PM# affirmation of compliance. Premarket 

number should always be the number that is on the listing record along with

a valid prefix denoting the application type (BD, BP, BK, BH, BM, BR, K, 

or P)

• PM# Affirmation of Compliance followed by the PMA Device Premarket

Approval Number

The affirmation and qualifier should be the Device Pre-Market 

Approval Number issued by FDA (CDRH/CBER) for the product 

identified in the FDA line. Premarket approval can be required of

devices if general controls are not sufficient to ensure safety and 

effectiveness and there is not enough information to establish a

performance standard. The prefix BP or BM is required for conducting 

a search in Center Views. 

• PM# Affirmation of Compliance followed by the PMN Device Pre-Market 

Notification Number (510(k))

The affirmation and qualifier should be the Device Pre-Market

Notification Number or 510(k) number issued by FDA (CDRH/CBER)

for the product identified in the FDA Line. The prefix BK or DK is 

needed for conducting a search in Center Views application. 

A prefix of BR is used for Direct De Novo devices, and a prefix of BH is 

used for Humanitarian Device Exemptions. 

Other Affirmations of Compliance applicable to Devices include:

For a medical device subject to registration and listing (21 CFR 1.78 

(g)):

DFE: Affirmation of compliance code applies to the Device 

Foreign Manufacturer Registration Number
14

DEV: Affirmation of compliance code applies to the Device 

Domestic Manufacturer Registration number. 

DLS: Affirmation of compliance code applies to the Device 

Listing Number. 

DDM: Affirmation of compliance code applies to the Device 

Domestic Manufacturer Registration Number.

Medical Device Component (21CFR 1.78 (j)): 

CPT: The Affirmation of compliance CPT without any qualifier 

applies when the article being imported is a device component that 

requires further processing or inclusion into a finished medical 

device. 

For additional clarification on devices, see the CDRH Device Initial 

Admissibility Job Aid. 

2. Import Alerts

The entry reviewer should determine if the foreign manufacturer or the biological 

product, drug, or device offered for import is listed on an active Import Alert and, 

if so, refer to that import alert for instructions. Import Alerts can be found the 

Center Views application. When a U.S. license is revoked or suspended, CBER 

will contact the Division of Import Operations Management (DIOM) and request 

this information be shared through an ORA issued import alert.

3. Review of Admissibility Requirements

a. Approved or Cleared Products

The entry reviewer should check to ensure that the foreign establishment 

holds an approved BLA, NDA, ANDA, PMA, or cleared 510(k) for the 

product. If the establishment does not hold the approved application or 510(k) 

clearance, the entry reviewer should refer the line with a request for detention 

(DTR). (For approval status of imported intermediates, active pharmaceutical 

ingredients, bulk substances, or other biologics for further manufacturing use, 

see section 3.c. below.) 

b. Investigational Products

The entry reviewer should check to ensure that the foreign establishment 

holds an IND or IDE in effect for the product. Center Views (CBER tab --

"application number" field) should be used to verify CBER INDs and IDEs. If 

Center Views is not operational for any reason, or if there are any questions, 

reviewers should contact CBER, OCBQ, DCM (see Part VI.B. for program 

contact information). If the establishment does not have an IND or IDE in 

effect for its investigational products, the entry reviewer should refer the line 
15

with a request for detention (DTR)1

. (For approval status of imported 

intermediates, active pharmaceutical ingredients, bulk substances, or other 

biologics for further manufacturing use, see section 3.c. below.) 

c. Imported intermediates, active pharmaceutical ingredients, bulk substances, or 

other biologics for further manufacturing use

Unless the manufacturer is subject to the import-for-export provisions, as 

discussed in section d. below, intermediates, active pharmaceutical 

ingredients, bulk substances, or other biologics for further manufacturing may 

also use an AofC Code as described in sections 3a and 3b above. This is true 

even if the foreign manufacturer does not hold the approval, clearance, or 

investigational application for the final biological or drug product, as is the 

case with contract manufacturers. If there is any question about the link 

between the foreign manufacturer and the AofC Code provided, contact the 

importer to request clarification.

d. Import-for-Export Products

1. The AofC code for import-for-export products is: "IFE." This 

affirmation allows for importation of violative articles (including drug 

and device components) under the import-for-export provisions of the 

FD&C Act. The article must be incorporated, by the initial owner or 

consignee, into a product for export; and the product must be exported 

from the United States by the initial owner or consignee, in accordance 

with the provisions of Sections 801(e) and 802 of the FD&C Act, or 

Section 351 of the PHS Act. Drugs and Devices

The Import-for-Export provisions of Section 801(d)(3) of the FD&C 

Act permit a person to import unapproved or otherwise non-compliant 

drug components and device components as long as the imported item 

is further processed or incorporated into products that are exported 

from the U.S. The entry reviewer should refer to the RPM, Chapter 9 ,

"Import for Export Subchapter" 

(http://www.fda.gov/downloads/ICECI/ComplianceManuals/Regulator

yProceduresManual/UCM074300.pdf) and IOM Sections 6.2.3.4.1-

6.2.3.4.3 for handling these entries." 

(http://www.fda.gov/downloads/ICECI/ComplianceManuals/Regulator

yProceduresManual/UCM074300.pdf) for handling these entries.

2. Blood, Blood Components, Source Plasma or Source Leukocytes or 

components, etc. thereof,

Section 801(d)(4) of the FD&C Act places additional limitations on 

the import-for-export of blood, blood components, Source Plasma, 

Source Leukocytes, or a component, accessory, or part thereof. These 

products are permitted importation under Section 801(d)(3) of the 

 

1 An IND is not considered to be "in effect" for any investigational products that are subject to an 

investigation which has been placed on clinical hold. See 21 CFR 312.40(b)(1) and 312.42.
16

FD&C Act if the importation complies with licensing requirements of 

the PHS Act or if FDA permits the importation under appropriate 

circumstances and conditions through an FDA-approved import-forexport request.

If shipments of blood, blood components, Source Plasma, or Source 

Leukocytes, etc., are identified as import-for-export, the entry reviewer 

should request a copy of the CBER approval letter from the importer 

or contact CBER, OCBQ, DCM (see Part VI.B. for program contact 

information) to determine if approval has been granted pursuant to 

Section 801(d)(4). If CBER has not approved the importation, the 

entry reviewer should refer the line with a request for detention (DTR). 

See Part Vfor charges and actions. 

e. Samples Offered for Import

1. Product Samples For Lot Release

Under 21 CFR 610.2, manufacturers may be required to submit to 

CBER samples from all lots of a licensed biological product, together 

with the protocols showing results of applicable tests when deemed 

necessary by the Director, CBER. For most biological products, CBER 

has required the submission of this information both in support of a 

license application and for continued lot release following product 

license application approval.

Samples of imported biological products that are offered for entry 

and consigned to the Sample Custodian at CBER pursuant to 

21 CFR 610.2 (official release of requested samples) for lot release 

action should not be referred with a request for detention (DTR).

2. Other Samples Consigned to the CBER Sample Custodian

If samples of products are offered for entry and provided to the CBER 

Sample Custodian for reasons other than CBER's lot release program 

under 21 CFR 610.2 (e.g., premarket testing, pursuant to FDA request, 

etc.), the samples should not be referred with a request for 

detention (DTR) as long as the consignee is the Sample Custodian 

at CBER.

3. Drug and Biologics Provisions Relating to Samples

Drugs (including biologics) intended solely for testing in vitro or 

laboratory research in animals may be shipped in accordance with 21 

CFR 312.160. These drug products should be labeled:

"CAUTION: Contains a new drug for investigational use only in 

laboratory research animals, or for tests in vitro. Not for use in 

humans."

In addition, 21 CFR 312.2(b)(2)(i) and 21 CFR 312.160 exempt blood 

grouping reagents, reagent red blood cells, and anti-human globulin 

intended for use in clinical investigations when the product is intended 
17

to be used in a diagnostic procedure that confirms the diagnosis made 

by another, medically established, diagnostic product or procedure and 

the product is shipped in compliance with 21 CFR 312.160. If these 

products are shipped for investigational in-vitro diagnostic use, they 

must be labeled:

"CAUTION: Contains a biological product for investigational in vitro 

diagnostic tests only." If the product appears to be inappropriately 

labeled, the entry reviewer should refer the line with a request for 

detention (DTR). See Part V for charges and actions.

4. Device Provisions Relating to Samples

Devices (including biologics regulated as devices) intended for testing 

in vitro or on laboratory animals must be labeled in accordance with 

21 CFR 812.5(c). The label must read:

"CAUTION-Device for investigational use in laboratory animals or 

other tests that do not involve human subjects."

Shipments of IVDs for other research or testing purposes are also 

permitted under 21 CFR 809.10(c)(2):

• For a product in the laboratory research phase of development, and 

not represented as an effective IVD, all labeling bears the 

statement, prominently placed:

"For Research Use Only. Not for use in diagnostic procedures."

• For a product being shipped or delivered for product testing prior 

to full commercial marketing (for example, for use on specimens 

derived from humans to compare the usefulness of the product 

with other products or procedures which are in current use or 

recognized as useful), all labeling bears the statement, prominently 

placed:

"For Investigational Use Only. The performance characteristics of 

this product have not been established."

If the product appears to be inappropriately labeled, the entry reviewer 

should refer the line with a request for detention (DTR). See Part V for 

charges and actions.

f. Biological Specimens for Clinical Testing or for Basic Scientific Research

Biological specimens that are used only for testing in a clinical laboratory or 

for basic scientific research and that are not articles intended for the 

prevention, treatment, diagnosis, or cure of diseases, injuries, or conditions in 

human beings, are not considered to be biological products subject to 

licensure with FDA in accordance with Section 351(a) of the PHS Act, nor 

would they appear to be a drug or device as defined in Sections 201(g) and 

(h), respectively, of the FD&C Act (see "Importing CBER-Regulated Products 

into the United States: Clinical Laboratories and Basic Scientific Research" at 
18

https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulator

yInformation/ComplianceActivities/BiologicsImportingExporting/ucm390716

.htm Thus, these specimens are not subject to FDA jurisdiction; and the filer 

should specify the entry is not subject to FDA regulation by "disclaiming" the 

entry (see section 6.2.3.6.1 of the Investigations Operations Manual).

If a shipment of one of these specimens is encountered, you may wish to 

consider whether the size and quantity appear to qualify as specimens for 

clinical testing or for basic scientific research. For example, a shipment of 1 to 

30 tubes containing 10 ml of plasma, serum, or blood would be considered 

samples for clinical testing. Import Divisions also may want to verify that the 

consignees are clinical testing laboratories or research facilities actually 

engaged in clinical laboratory testing or laboratory research. (Some U.S. firms 

do have their own in-house testing and research laboratories, so the fact that it 

is being shipped to a biologics firm does not necessarily mean it is not going 

to a research facility.) If the Import Division or entry reviewer suspects 

diversion, they should contact CBER, OCBQ, DCM (see Part VI.B. for 

program contact information).

g. Blood and Blood Components for Autologous Use Only

Entries of unlicensed human blood or blood components (e.g., whole blood, 

red blood cells, plasma) for autologous use only, should not be referred to 

compliance with a request for detention, provided the manufacturer of the 

product does not ship autologous blood products in interstate commerce on a 

routine or regular basis2 and provided that the autologous blood products are 

for transfusion purposes only, have not been further processed or manipulated, 

and are labeled in accordance with the labeling regulations applicable to 

autologous blood, which are located at 21 CFR 606.121(i).

h. "Short Supply" Products

The short supply provisions of 21 CFR 601.22 allow an unlicensed 

establishment to conduct the initial and partial manufacturing of a biological 

product at places other than the establishment approved in the BLA, provided 

all requirements of 21 CFR 601.22 are fulfilled.

Currently, products that may be supplied under 21 CFR 601.22 are:

• recovered plasma, 

• red blood cells, 

• snake venoms, and 

• hymenopteran (bee) venoms. 

To qualify as short supply products, these products must be for further 

manufacture only and not for final distribution.

 

2 See Ref. 11 for further discussion of routine or regular basis.
19

The entry reviewer should verify that a short supply agreement between the 

collection facility and the manufacturer of the final, licensed product is in 

effect prior to or at the time of shipment (see 21 CFR 601.22). This may be 

obtained by contacting the importer of record or the consignee. A short supply

agreement is generally between the unlicensed initial or partial manufacturer 

and the manufacturer of the final, licensed product; short supply agreements 

are not valid if they are entered between a plasma broker or broker(s) and the 

manufacturer of a final, licensed product.

If there is no valid short supply agreement between the appropriate parties or 

the product is not correctly labeled, the entry reviewer should refer the line 

with a request for detention (DTR). See Part V for charges and actions.

i. Recovered Plasma, Plasma, and Serum Not The Subject of a Short Supply 

Agreement and Intended for Further Manufacture into a Device

Recovered plasma, plasma, and serum that are not the subject of a short 

supply agreement and are intended for further manufacture into a device, are

considered device components, and are processed under the Medical Device 

Industry Codes and the Center for Devices and Radiological Health (CDRH) 

import processes. Examples include serum or plasma intended for further 

manufacture into in-vitro diagnostic reagents such as clinical chemistry 

controls. The immediate container should be properly labeled as described in 

the labeling regulations (see 21 CFR 606.121 and 610.40).

If there is a question concerning the device components in the entry, labeling

may be examined for: 

• The name of the product (21 CFR 1.78 (a)); 

• Name(s), address(es), and registration number(s) of establishment(s)

[21CFR 1.72(b)] collecting, preparing, labeling, or pooling the source 

material [21 CFR 606.121(c)(2)]; 

• Intended use and appropriate caution statements (21 CFR 1.72 (a)(3)):

 Statement "Caution: For Further Manufacturing Use as a Component 

of, or to Prepare, a Medical Device." [21 CFR 610.40(c)(3)]. If the 

product is recovered plasma and there is a reactive screening test for 

evidence of infection due to communicable disease agent(s) or is 

collected from a donor with a previous record of a reactive screening 

test, the recovered plasma must be labeled as appropriate: "Caution: 

For Further Manufacturing Use as a Component of a Medical Device 

for Which There are No Alternative Sources" or "Caution: For Further 

Manufacturing Into In Vitro Diagnostic Reagents for Which There are 

No Alternative Sources." [21 CFR 606.121(e)(4)(ii); 21 CFR 

610.40(h)(2)(ii)(E)] 

 For recovered plasma not meeting the requirements for manufacture 

into licensable products, the statement: "Not for Use in Products 
20

Subject to License Under Section 351 of the Public Health Service 

Act." [21 CFR 606.121(e)(4)(iii)] 

If the product is inappropriately labeled, the entry reviewer should refer the 

line with a request for detention (DTR). See Part V for charges and actions.

Other U.S. Government Agencies' Requirements

On occasion, a product offered for import may be held or detained due to another 

agency's requirements. For example, a product may be held or detained because it 

needs an Etiological Agent Import Permit from the Centers for Disease Control 

and Prevention (see http://www.cdc.gov/od/eaipp/) or an Animal Health or 

Veterinary Biologics Permit from the Animal and Plant Health Inspection Service 

in the United States Department of Agriculture (see 

http://www.aphis.usda.gov/permits/). If the Import Division discovers that a 

product is being held because it needs such a permit, the entry reviewer should 

advise that these are not FDA's requirements but are those of another U.S. 

government agency and that is the company's responsibility (not FDA's) to obtain 

such a permit.

B. Documents That May Be Requested

If no Affirmation of Compliance is provided, or if questions relating to the entry arise, 

the entry reviewer may request relevant documents that provide sufficient information to 

make an admissibility decision. Documents that may be requested include, for example:

• The FDA approval (approved BLA, NDA, ANDA, PMA), clearance (cleared 

510(k)), or active investigational approval or exemption (active IND or IDE) for 

an approved, cleared, or investigational product. 

• Labeling for the product 

• Short supply agreement 

• Import-For-Export approval letter under Section 801(d)(4) (where applicable) 

If you request labeling, standards for labeling of products are found in several places, 

including:

• 21 CFR 610 subpart G provides general labeling standards for biological 

products. Additional labeling requirements can be found in 21 CFR 610.40. 

• 21 CFR 606.121 and 21 CFR 606.122 specify labeling requirements for blood and 

blood components, except that: 

o 21 CFR 640.74(b)(4), and 640.76 specify labeling requirements for Source 

Plasma. 

• 21 CFR 640.84 specifies labeling requirements for albumin. 

• 21 CFR 640.94 specifies labeling requirements for plasma protein fraction 

(human). 
21

• 21 CFR 660.28 specifies labeling requirements for blood grouping reagents. 

• 21 CFR 660.35 specifies labeling requirements for reagent red blood cells. 

• 21 CFR 660.2(c) specifies labeling requirements for antibody to Hepatitis B 

Surface Antigen. 

• 21 CFR 660.45 specifies labeling requirements for Hepatitis B Surface Antigen. 

• 21 CFR 660.55 specifies labeling requirements for anti-human globulin. 

• 21 CFR 201 specifies the labeling requirements for drug products, including 

biological drug products. Labeling requirements for investigational new drugs are 

set out at 21 CFR 312.6.

• 21 CFR Sections 801 and 809 specify the labeling requirements for medical 

devices.

Contact CBER, OCBQ, DCM (see Part VI.B. for program contact information) if you 

have further questions concerning the labeling of the entry.

C. Special Circumstances

1. Counterfeit Products

If you suspect that a product offered for import is counterfeit, contact CBER, 

OCBQ, DCM (see program contacts at Part VI.B.) to establish an appropriate plan 

of action.

2. American Goods Returned (also referred to as U.S. Goods Returned)

American Goods Returned (AGR), also referred to as U.S. Goods Returned 

(USGR), is a term used for the formal declaration of goods manufactured in the 

United States that have been previously exported and are now being returned. If a 

product offered for import has been returned, rejected, or has a complaint file, the 

Import Division should carefully review that entry to determine the reason for the 

return, rejection, or complaint. In addition, products that are identified as ARG 

should travel with documentation demonstrating that the product was kept under 

the appropriate storage conditions while in foreign storage and during shipment 

back to the United States. Note that if the product is a drug, section 801(d)(1) of 

the FD&C Act applies, and the product may be imported by the U.S. 

manufacturer. In accordance with the Supplemental Guide, Intended Use Code

920.000 for return to the United States (US Goods Returned) should be submitted, 

and there is no requirement for an AofC. 

If there is reason to believe that an appearance of violation may exist, then consult 

with CBER for assistance, if needed. Goods should be detained with the 

appropriate charge when they appear violative. If there are any questions, contact 

CBER, OCBQ, DCM (see Part VI.B. for program contact information).
22

3. Medical Emergency

Section 801(d)(2) of the FD&C Act permits the Secretary to authorize the 

importation of a drug, which would otherwise be prohibited, if the drug is 

required for emergency medical care. Import Divisions should use discretion in 

detaining a product offered for import if its use is required for a medical 

emergency.

Import entries coming under this provision may be submitted using IUC 940.000

(Compassionate Use/Emergency Device) or 140.000 ((for Improving living 

conditions during a natural disaster).

4. Influenza Virus Vaccine Entries for the Annual Strain Changes

For Influenza Virus Vaccine imported in advance of approval of BLA 

supplements for the annual strain changes, the vaccine manufacturer should

submit a request to CBER identifying the product, quantities, storage conditions, 

and other relevant information. CBER will advise the Division of Import 

Operations Management (DIOM), and the manufacturer, once the import request

has been deemed acceptable and the submitted reconditioning plan (Form FDA 

766) for the entry has been accepted. This allows a firm to import and recondition 

the bulk influenza strains while held under bond. 

The applicable Import Division will notify the importer of the acceptance of the 

reconditioning plan. Once the BLA supplement is approved, the entries may be 

released.

Questions on the process for importing Influenza Virus Vaccine shipments should 

be directed to: ORADIOVaccineTeam@fda.hhs.gov

Table of Contents

PART IV - ANALYTICAL

If sample collection is necessary, specific instructions will be provided, including the 

laboratory or laboratories to which the sample should be sent. Consult with CBER 

program contacts identified in Part VI, before collecting samples for agency analysis,

When sample collection is necessary, CBER will notify the Office of Regulatory 

Science, Office of Medical Products, Tobacco, and Specialty Laboratory 

Operations/ORA. 
23

If samples are to be evaluated by CBER, contact the CBER Sample Custodian (240-402-

9156) before shipping any samples. No one is available to receive samples over the 

weekend. Samples evaluated by CBER should generally be shipped to:

CBER Sample Custodian/FDA (FEI: 1000385447)

10903 New Hampshire Ave

Silver Spring, MD 20993-0002

Collect any samples of a potentially bio-hazardous nature in accordance with IOM 1.5.5, 

“Microbiological Hazards”.

Table of Contents

PART V - REGULATORY/ADMINISTRATIVE STRATEGY

A. CHARGES3

1. Approved/Licensed/Cleared and Investigational Products regulated by CBER

A product offered for import should be detained if the foreign establishment does 

not hold an approved BLA, NDA, ANDA, PMA, a cleared 510(k), or does not 

hold an IND or IDE in effect for the product that is described in the entry (see 

limited exception in Part III.A.3.c. for imported intermediates, active 

pharmaceutical ingredients, bulk substances, or biologics for further processing), 

or the product does not otherwise appear to be in compliance with the laws

enforced by FDA. Consider the type and the intended use of the biological 

product.

If the product appears to be a biological product, include the following statement 

on the Notice of FDA Action:

• The article is subject to refusal of admission under section 801(a)(3) of the 

Federal Food, Drug, and Cosmetic Act (FD&C Act) because it appears to 

be a biological product for which a biologics license is not in effect under 

the Public Health Service Act, Part F, Subpart 1-Biological Products,

Section 351(a), and it is not the subject of an Investigational New Drug 

application that is in effect. Therefore, it appears to be a new drug under 

201(p) of the FD&C Act that it is in violation of section 505(a) of the 

FD&C Act because it lacks a new drug approval and because it is 

 

3 These charges are not all-inclusive. For example, should an entry reviewer encounter an appearance of 

adulteration, e.g., for failure to comply with current good manufacturing practice, see Section 501(a)(2)(B) 

charge under detention in Part V.B.
24

misbranded under section 502(f)(1) of the FD&C Act because it fails to 

bear adequate directions for use [IMPORT DETENTION VIOLATION 

CODE = NO LICENSE]

If the product appears to be a drug, include the following statement on the Notice 

of FDA Action:

• The article appears to be a new drug without an approved new drug 

application. [IMPORT DETENTION VIOLATION CODE = 

UNAPPROVED].

If the product appears to be a device, include the following statement on the 

Notice of FDA Action:

• The article is subject to refusal of admission pursuant to Section 801(a)(3) 

in that the device appears to be a Class III device and does not appear to 

have in effect an approved application for premarket approval pursuant to 

Section 515 of the Act, or an exemption pursuant to Section 520(g)(1) 

[Adulteration, Section 501(f)(1)(B)]. [IMPORT DETENTION 

VIOLATION CODE = NO PMA]

• The article appears to be a class III device without an approved application

for premarket approval, and/or a notice of completion of product 

development protocol filed per section 515(b) or exempt per section

520(g)(1).).) of the Act.). [Adulteration, Section 501(f)(1)(A)], [IMPORT 

DETENTION VIOLATION CODE=NO PMA/PDP]

In addition, if these products appear to be misbranded, include one of the 

following statements on the Notice of FDA Action:

• The labeling for this article appears to be false or misleading. 

[IMPORT DETETION VIOLATION CODE = FALSE]

• The article appears to lack adequate directions for use. [IMPORT 

DETENTION VIOLATION CODE = DIRECTIONS]

2. Import-for-Export Products

Detain all products identified as import-for-export if they do not comply with 

sections 801(d)(4) of the FD&C Act. Consider the type and the intended use of 

the product.

If the product appears to be a biological product, include the following statement 

on the Notice of FDA Action:
25

• The article is subject to refusal of admission under section 801(a)(3) of 

the Federal Food, Drug, and Cosmetic Act (FD&C Act) because it 

appears to be a biological product for which a biologics license is not 

in effect under the Public Health Service Act, Part F, Subpart 1-

Biological Products, Section 351(a), and it is not the subject of an 

Investigational New Drug application that is in effect. Therefore, it 

appears to be a new drug under 201(p) of the FD&C Act that it is in 

violation of section 505(a) of the FD&C Act because it lacks a new 

drug approval and it is misbranded under section 502(f)(1) of the 

FD&C Act because it fails to bear adequate directions for use 

[IMPORT DETENTION VIOLATION CODE = NO LICENSE]. 

If the product appears to be a drug, include the following statement on the Notice 

of FDA Action:

• The article appears to be a new drug without an approved new drug 

application. [IMPORT DETENTION VIOLATION CODE = 

UNAPPROVED]. 

If the product appears to be a device, include the following statement on the 

Notice of FDA Action:

• The article is subject to refusal of admission pursuant to Section 

801(a)(3) in that the device appears to be a Class III device and does 

not appear to have in effect an approved application for premarket 

approval pursuant to Section 515 of the Act, or an exemption pursuant 

to Section 520(g)(1) [Adulteration, Section 501(f)(1)(A)]. [IMPORT 

DETENTION VIOLATION CODE = NO PMA]

• The article appears to be a class III device without an approved 

application for premarket approval, and/or a notice of completion of 

product development protocol filed per section 515(b) or exempt per 

section 520(g)(1).).) of the Act.). [Adulteration, Section 501(f)(1)(A)], 

[IMPORT DETENTION VIOLATION CODE=NO PMA/PDP]

In addition, if these products appear to be misbranded, include one of the 

following statements on the Notice of FDA Action:

• The labeling for this article appears to be false or misleading. 

[IMPORT DETETION VIOLATION CODE = FALSE]

• The article appears to lack adequate directions for use. [IMPORT 

DETENTION VIOLATION CODE = DIRECTIONS]

3. Samples of Drugs, Devices and Biological Products
26

This section does not apply to Import of Product Samples for Lot Release, Other 

Samples Consigned to the CBER Sample Custodian, or to Biological Specimens 

for Clinical Testing or for Basic Scientific Research. 

Only detain entries misidentified as samples that appear to be Drugs, Devices or 

Biological products. 

If the product appears to be a biological product, include the following statement 

on the Notice of FDA Action:

• "The article is subject to refusal of admission under section 801(a)(3) 

of the Federal Food, Drug, and Cosmetic Act (FD&C Act) because it 

appears to be a biological product for which a biologics license is not 

in effect under the Public Health Service Act, Part F, Subpart 1-

Biological Products, Section 351(a), and it is not the subject of an 

Investigational New Drug application that is in effect. Therefore, it 

appears to be a new drug under 201(p) of the FD&C Act that it is in 

violation of section 505(a) of the FD&C Act because it lacks a new 

drug approval and it is misbranded under section 502(f)(1) of the 

FD&C Act because it fails to bear adequate directions for use 

[IMPORT DETENTION VIOLATION CODE = NO LICENSE]. 

If the product appears to be a drug, include the following statement on the Notice of 

FDA Action:

• The article appears to be a new drug without an approved new drug 

application. [IMPORT DETENTION VIOLATION CODE = 

UNAPPROVED]

In addition, if these products appear to be misbranded, include one of the 

following statements on the Notice of FDA Action:

• The labeling for this article appears to be false or misleading. 

[IMPORT DETETION VIOLATION CODE = FALSE]

• The article appears to lack adequate directions for use. [IMPORT 

DETENTION VIOLATION CODE = DIRECTIONS]

4. Short Supply Products

Detain products purporting to be "short supply" products if there does not appear 

to be a short supply agreement in effect, or if the products do not appear to be 

properly labeled.
27

If there does not appear to be a short supply agreement and the product is subject 

to licensure, the product is an unapproved new drug and should be charged in 

accordance with Part V.A.1. If the product is intended for further manufacture 

into a finished product that is not subject to licensure, see Part V.A.5. below.

Products, including blood and blood components, intended for further 

manufacture into licensed biological products must be labeled "Caution: For 

Manufacturing Use Only." Recovered Plasma for further manufacture must be 

labeled, as applicable, "Caution: For Manufacturing Use Only” or “Caution: For 

Use in Manufacturing Noninjectable Products Only, " or “Not for Use in Products 

Subject to Licensure Under Section 351 of the Public Health Service Act.” (see 21 

CFR 606.121(c)(10) and 606.121(e)(4)(ii))

In addition, if these products appear to be misbranded, include one of the 

following statements on the Notice of FDA Action:

• The labeling for this article appears to be false or misleading. [IMPORT 

DETETION VIOLATION CODE = FALSE].

• The article appears to lack adequate directions for use [IMPORT 

DETENTION VIOLATION CODE = DIRECTIONS].

5. Recovered Plasma, Plasma and Serum Not The Subject of a Short Supply 

Agreement and Intended for Further Manufacture into unlicensed device products

Recovered plasma, plasma and serum, that are not subject to a short supply 

agreement, and are intended for further manufacture into device, are considered 

device components and are processed under the Medical Device Industry Codes 

and the Center for Device and Radiological Health (CDRH) import processes.

The immediate container should be labeled in accordance with the applicable 

labeling requirements in 21 CFR 606.121 and 21 CFR 610.40.

In addition, if these products appear to be misbranded, include one of the 

following statements on the Notice of FDA Action:

• The labeling for this article appears to be false or misleading. 

[IMPORT DETETION VIOLATION CODE = FALSE]

• The article appears to lack adequate directions for use. [IMPORT 

DETENTION VIOLATION CODE = DIRECTIONS]

B. ACTIONS

For violative imported CBER regulated products that are still in import status, the 

enforcement options available include:
28

Detention Detention of biological products, drugs, and devices based on the 

appearance of violations as described in section 801(a) of the 

FD&C Act. 

Refusal Refusal of biological products, drugs, and devices based on the 

appearance of violations as described in section 801(a) of the 

FD&C Act. Product can be re-exported or destroyed.

Administrative 

Destruction

Refused drugs valued at $2500 or less where FDA makes a 

determination of a violation, may be destroyed by FDA without 

opportunity for re-export. 

DWPE –Import 

Alert

Any FDA unit may recommend DWPE (or recommend additions 

to existing import alerts) whenever there is information that would 

cause future shipments of biological products, drugs, or devices 

offered for entry to appear violative under laws administered by 

FDA. See RPM Chapter 9, “Detention Without Physical 

Examination” Subchapter, regarding procedures for DWPE.

Recommendations for DWPE should be submitted in writing with 

supporting information to the Division of Import Operations

Management.

Warning Letters Please consult with CBER (see program contacts, part VI.C.)

Bond Actions Bond actions may be initiated by U.S. Customs and Border 

Protection (CBP) when an entry is distributed prior to FDA 

release and cannot be redelivered, or when an article has been 

detained and refused and the article is not destroyed or exported in 

accordance with the requirements of the law. Import Divisions

should work closely with the responsible CBP office. See IOM 

6.2.7.11, “Bond Action” and RPM Chapter 9 “Bond Actions”

Subchapter.

Custom Seizures CBP has seizure authority over merchandise whose importation or 

entry is subject to any restriction or prohibition which is imposed 

by law relating to health or safety and may be seized in 

accordance with 19 USC 1595a(c)(2)(A). Provide CBP with 

charge code, pertaining to health or safety.

Table of Contents

PART VI - REFERENCES/PROGRAM CONTACTS
29 

A. References

1. Investigations Operations Manual (IOM), Chapter 6 - Imports 

2. Import Alerts Listing 

3. Regulatory Procedures Manual, Chapter 9 - Import Operations/Actions 

4. Compliance Policy Guidance Manual, Chapter 2 – Biologics 

5. Lists of Licensed Products and Establishments, and approved in vitro diagnostic 

test kits

6. Alphabetical List of Licensed Establishments including Product Approval Dates 

7. Alphabetical List of Licensed Products 

8. Complete List of Donor Screening Assays for Infectious Agents and HIV 

Diagnostic Assays 

9. Complete List of Currently Approved Premarket Approvals (PMAs) 

10. Complete List of substantially equivalent 510(k) Device Applications

11. Memo to All Registered Blood Establishments, Dated February 12, 1990, Subject: 

Autologous Blood Collection and Processing Procedures 

B. Program Contacts

CBER/OCBQ/DCM ORA/ OEIO

at Phone: (301) 796-5270 

CBERImportInquiry@fda.hhs.gov Fax: (301) 827-3670 

Maria Anderson: (240) 402-8883 Division of Import Operations 

Robert Sausville: (240) 402-9076 Management

Samuel Chan (301) 796-2283 

Jeffrey Hilgendorf (313) 393-2019 

Division of Systems Solutions, Import 

Systems Branch (DSS, ISB)

ORAOISMDSSIMPCOMPLSYSBR@fda.hhs.gov

Table of Contents 

PART VII - CENTER RESPONSIBILITY/PROGRAM EVALUATION

CBER, OCBQ, will work cooperatively with ORA, and the Biologics Program

Committee, concerning imported biological products, drugs, and devices covered under 

this compliance program.

The ORA Imports annual workplan, developed by CBER and ORA, provides overall 

resource allocations. However, in some circumstances, FDA may examine and/or sample 
30 

the product offered for import, which may result in unplanned import activities taking 

more or less time than estimated in the workplan. In such a circumstance, the CBER 

should be contacted for further instructions. 

As is customary, ORA continues to have the primary responsibility for ensuring: 

1. That the program strategies, priorities, and procedures articulated in this 

compliance program are followed by the ORA staff, and 

2. Potential problems or needs for policy/program clarification are brought to the 

attention of CBER, OCBQ. 

CBER and ORA jointly coordinate activities to achieve industry compliance with 

applicable laws, and regulations. 

CBER, OCBQ, will continue to use accomplishment data from the ORA Operational and 

Administrative System for Import Support (OASIS), On-Line Reporting Analysis and

Decision Support System (ORADSS) Import Systems, and Field Accomplishment and 

Compliance Tracking System (FACTS), requests for policy decisions/clarification 

received from the public or the industry, and input from CBER scientific and product 

experts to aid industry and the field in the development of a consistent import compliance 

program that meets all applicable regulations.

Table of Contents 

Attachment A: Explanation of Terms Used in This Program 

Autologous Blood – Autologous blood is blood collected from an individual and intended 

for reinfusion to the same individual. 

Biologics License Application (BLA) - To obtain a biologics license under section 351 of 

the Public Health Service Act for any biological product, a manufacturer submits a 

biologics license application under 21 CFR 601.2, which requires a demonstration that 

the manufactured product meets the prescribed requirements of safety, purity, and 

potency. 

Investigational Device Exemption (IDE) - Once in effect, an IDE allows the shipment of 

an unapproved device for use in a clinical investigation. 21 CFR 812 are the IDE 

regulations. 

Investigational New Drug Application (IND) - 21 CFR 312.40(a) An investigational new 

drug may be used in a clinical investigation if the following conditions are met: 

(1) The sponsor of the investigation submits an IND for the drug to FDA; the IND 

is in effect under paragraph (b) of this section; and the sponsor complies with all 

applicable requirements in this part and parts 50 and 56 with respect to the 

conduct of the clinical investigations; and 
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(2) Each participating investigator conducts his or her investigation in compliance 

with the requirements of this part and parts 50 and 56. 

In Vitro Diagnostic products (IVDs)(21 CFR 809.3(a)) - In vitro diagnostic products are 

those reagents, instruments, and systems intended for use in the diagnosis of disease or 

other conditions, including a determination of the state of health, in order to cure, 

mitigate, treat, or prevent disease or its sequelae. Such products are intended for use in 

the collection, preparation, and examination of specimens taken from the human body. 

These products are devices as defined in section 201(h) of the Federal Food, Drug, and 

Cosmetic Act (the act), and may also be biological products subject to section 351 of the 

Public Health Service Act.

Manufacture (21 CFR 600.3(u)) - All steps in the propagation or manufacture and 

preparation of products and includes, but is not limited to, filling, testing, labeling,

packaging, and storage by the manufacturer.

Manufacturer (21 CFR 600.3(t)) - Manufacturer means any legal person or entity 

engaged in the manufacture of a product subject to license under the act; "Manufacturer" 

also includes any legal person or entity who is an applicant for a license where the 

applicant assumes responsibility for compliance with the applicable product and 

establishment standards.

New Drug Application (NDA) - New drug application, or NDA is the application 

described under 314.50, including all amendments and supplements to the application. 

An NDA refers to "stand-alone" applications submitted under section 505(b)(1) of the 

Federal Food, Drug, and Cosmetic Act and to 505(b)(2) applications.

Premarket Approval Application (PMA) - An application for FDA approval to distribute 

a class III medical device submitted pursuant to section 515 of the FD&C Act and 21 

CFR 814, including all information submitted with or referenced therein.

Premarket Notification (510(k)) - A premarket notification application that is submitted 

to the FDA pursuant to section 510(k) of the FD&C Act and 21 CFR 807 to demonstrate 

that the medical device is substantially equivalent to a legally marketed Class I or Class II 

device.

Recovered Plasma - Recovered Plasma is derived from single units of Whole Blood, or 

Plasma, or as a by-product in the preparation of blood components from whole blood 

collection. It is an unlicensed raw material intended for use in the manufacture of both 

licensed and unlicensed products, such as licensed fractionation products for injection, 

licensed diagnostic products; and diagnostic products not subject to license, including 

clinical chemistry controls. A license is not required to manufacture, distribute, relabel, 

pool, or repack Recovered Plasma.

Short Supply - Under 21 CFR 601.22, a licensed biologic manufacturer may obtain 

certain materials that are manufactured at unlicensed facilities when the following 

conditions are met: (1) manufacturing at the unlicensed facility will be limited to the 

initial and partial manufacturing of a product for shipment solely to the licensee; (2) the 

unlicensed manufacturer is registered with FDA in accordance with registration and 
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listing provisions in 21 CFR parts 207 and 607; (3) the licensed product is in short supply 

due either to peculiar growth requirements or scarcity of the source organism required for 

manufacturing; and (4) the licensed manufacturer can assure that, through inspections, 

testing, or other arrangements, the product made at the unlicensed facility will be made in 

full compliance with applicable regulations.

Source Leukocytes - Source Leukocytes is defined as human leukocytes (white blood 

cells) prepared manually from Whole Blood or collected by apheresis and intended as 

source material for further manufacturing use.

Source Plasma (21 CFR 640.60) - Source Plasma is defined as the fluid portion of 

human blood collected by plasmapheresis and intended as source material for further 

manufacturing use. The definition excludes single donor plasma products intended for 

intravenous use.