U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

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Inspection of U.S. Veterinary Biologics Licensed and Permitted Establishments 

1. Purpose and Background 

This memorandum provides guidance to licensee/permittees and other regulatory 

agencies (domestic or international) regarding the Center for Veterinary Biologics’ (CVB) 

onsite inspections and may be used as a guide for self-inspections to determine 

compliance with the Virus-Serum-Toxin Act (21 U.S.C. 151-159). The Virus-Serum-Toxin 

Act requires each manufacturer of a veterinary biological product to be issued a U.S. 

Veterinary Biologics Establishment License. The premises listed on the Establishment 

License, the methods of preparation of the veterinary biological product and equipment 

used, all activities within each establishment, and qualification of personnel are defined in 

documents filed with CVB. Regulations in title 9, Code of Federal Regulations (9 CFR), part 

115 give authority for any USDA inspector to enter any establishment where any biological 

product is being prepared, at any hour during the day or night, and inspect without 

previous notification. 

The Virus-Serum-Toxin Act authorizes the Secretary of Agriculture, through the Animal 

and Plant Health Inspection Service (APHIS), CVB to license and inspect all veterinary 

biologics. No worthless, dangerous, contaminated, or harmful product may be licensed, 

produced, or distributed. Facilities, equipment, processes, and personnel associated with 

the manufacturing, testing, packaging, and distribution of veterinary biological products 

are subject to regular, unannounced onsite inspections by representatives of CVBInspection and Compliance staff. The inspection process, with the CVB controlled testing 

of serials, rigorously assesses veterinary biological products manufactured, quality control 

tested, packaged, and distributed under the U.S. Veterinary Biologics Establishment 

License. The regulations promulgated by the Virus Serum Toxin Act describe the principles 

and practices of good manufacturing.

Pursuant to the Congressional Review Act (5 U.S.C. § 801 et seq.), the Office of 

Information and Regulatory Affairs designated this rule as a non-major rule, as defined by 

5 U.S.C. § 804(2). 

2. Document Status 

A. Issue Date: 12/08/2020 

B. This document replaces VSM 800.91 dated June 28, 2016. 
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

2 | Page

3. Reason for Reissuance 

A. This was updated for clarity and consistency with other regulatory documents by

adding definitions related to quality management and good manufacturing practices. 

Issuance of a Certificate of Inspection issued by CVB is also introduced in this 

guidance document. 

4. Authority and References 

A. Authorities 

• Virus-Serum-Toxin Act (37 Stat. 832-833, 21 U.S.C. 151-159)

• 7 CFR 371.4

• 9 CFR 101

• 9 CFR 102

• 9 CFR 103

• 9 CFR 104

• 9 CFR 105

• 9 CFR 108

• 9 CFR 109

• 9 CFR 112

• 9 CFR 113

• 9 CFR 114

• 9 CFR 115

• 9 CFR 116

• 9 CFR 117

 

B. References

• Animal Welfare Act

• Global Regulatory Framework Document. A guide created by Animal Health 

Institute (AHI) that compares the USDA methods/regulations to the Rules and 

Guidance for Pharmaceutical Manufacturers and Distributors (the Orange 

Book) compiled by the Inspection, Enforcement and Standards Division of 

Medicines & Health products Regulatory Agency and the Guide to Good 

Manufacturing Practice for Medicinal Products, prepared by the 

Pharmaceutical Inspection Convention, Pharmaceutical Inspection Cooperation Scheme (PICs). AHI is responsible for posting and maintaining this 

document.

• VSM 800.53, Release of Biological Products

• VSM 800.56, Disposal of Unsatisfactory and Undesirable Materials

• VSM800.57, Market Suspensions and Post Marketing Temperature Deviations

• VSM 800.59, Veterinary Biological Product Samples
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

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• VSM 800.60, Biological Products Returned to Licensed Establishments

• VSM 800.63, Personnel at Licensed Establishments

• VSM 800.64, Preparation of Experimental Products at Licensed Establishments

• VSM 800.74, Preparation and Distribution of Sterile Diluents

• VSM 800.78, Preparation and Submission of Facilities Documents

• VSM 800.115, Potency and Safety Testing by Unlicensed Facilities

• VSM 800.116, Target Animal Safety Testing Exemption

• VSM 800.210, Manufacturing Deviations Identified Prior to Marketing Release 

C. Definitions 

1) Quality Management is a wide-ranging concept covering all matters that 

individually or collectively influence the quality of a product. Manufacturers 

assume the responsibility for the quality of the veterinary biological product 

and that the product is fit for the intended use, as demonstrated during the 

licensing process, and comply with all applicable requirements throughout the 

product’s life cycle.

2) Quality Assurance is the totality of actions within the organization supporting 

quality management.

3) Good Manufacturing Practice is a system to ensure products are consistently 

produced and controlled. CVB oversight regarding periodic review of the 

licensee/permittee control is twofold. Sample submission and check testing by 

CVB provides one method of control. The second method is by routine onsite 

inspections.

4) Quality Control is the procedures used to ensure starting material, in-process 

material, and final use product conform to the established specifications 

required for consistent production.

5) Quality Risk Management is a systematic process to assess, control, 

communicate, and review the risks to the quality of the product across the 

product’s life cycle. It is used to develop the control strategy for each stage of 

manufacturing, from starting material to final distributed product.

6) Validation is the action of scientifically proving the procedures, processes, 

equipment, material, activities, and systems lead to the results of delivering a 

quality product. This includes continual assurance that a process remains in a 

state of control. Some examples are:

• Cleaning procedures

• Testing procedures 

• Production processes 
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

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• Equipment use 

• Computer systems 

7) Calibration is the demonstration that a particular instrument or device 

produces results within specified limits by comparison with those produced by 

a reference or traceable standard over an appropriate range of 

measurements.

8) Data Integrity is the overall accuracy, completeness, and consistency of data. 

5. Audience 

VS employees and members of the biologics industry. 

6. Guidance 

A. Process 

1) The inspection performed by CVB inspectors is in part to determine products 

were produced and tested by competent people using acceptable facilities, 

equipment, and validated processes. 

2) The inspection includes audits of related records, observations to substantiate 

information on file with CVB, and perambulation of ongoing operations. 

B. Findings 

1) Findings are listed under one of the 14 categories of inspection found in 

subsequent sections of this guidance.

a. Violations will be cited as per 9 CFR and may include the applicable section 

numbers. Additional 9 CFR citations may also apply. 

b. Violations will be classified as Serious, Less Serious, or Minor.

i. Serious – Violations of this degree may affect the quality of the product or 

products or may be willful.

ii. Less Serious – By repetition or situation, may affect quality of a product.

iii. Minor – Are not apt to affect quality of product but indicate laxity or error 

that could become more serious if not corrected. Numerous minor 

exceptions noted during the inspection indicate poor quality management 

and should be considered as having cumulative effect.
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

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c. The findings documented as a result of audits and observations for each 

inspection category should not be considered limiting or all-inclusive.

2) CVB Inspectors provide a summary of finding to the regulated entity after each indepth inspection. 

3) A written response from the licensee/permittee regarding corrective and 

preventive actions taken for the documented findings are required be submitted 

to CVB. This may require more than one response from the licensee/permittee.

4) Certificates of Inspection may be issued indicating the manufacturing sites were

inspected under the laws of the United States of America and comply with the 

principles and practices of USDA good manufacturing.

C. Following is the list of inspection categories, with audits and observations for each. 

The list also includes information that may be reviewed during the annual 

Administrative Inspection Reviews. APHIS inspectors may use this list for guidance 

when conducting inspections. These items may also be beneficial for establishing selfinspections. The overarching regulation regarding inspection of establishments is

9 CFR 115.1.

1) Licenses and Permits 

a. Audits

i. Review the ownership, parent company, and subsidiary and division 

relationships with the firm’s official in charge. If applicable, discuss any 

future changes or mergers and impacts to production and testing. 

[Reference: 9 CFR 114.1]

ii. Verify addresses, locations, and other information on the license. Confirm 

all stages of production are conducted within licensed premises. 

[Reference: 9 CFR 114.1]

iii. Review U.S. Veterinary Biological Product Permits for Research and 

Evaluation and any permits for the importation or transportation of 

organisms or vectors issued to the licensee and compare with information 

on file at CVB. 

1. Ask for any additional permits the firm may have.

2. Audit the firm’s records for compliance with special requirements listed 

on the permits and with the regulations covering importation for 

research and evaluation.
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

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3. Determine if any of the permits expired.

b. Observations

i. Note the location of buildings and equipment used to produce, test, and 

store products to be sure that all premises are properly identified on the 

establishment license. Note any change in ownership, location, or 

operation of the establishment. [Reference: 9 CFR 108.1]

ii. Verify every product observed in production or testing on the licensed 

premises has a license or permit. Ensure products prepared under the 

Food and Drug Export Reform and Enhancement Act do not adversely 

impact the preparation of licensed/permitted veterinary biological 

product. [Reference: 9 CFR 114.2(b)]

iii. If applicable, review non-biological products prepared in the facility and 

determine if there is any adverse impact to the preparation of 

licensed/permitted veterinary biological product. [Reference: 9 CFR 103.1]

iv. Review permit restrictions and determine if the permittee is in compliance 

with these restrictions for imported products for distribution and sale. 

v. Inspect facilities where research material imported under permit is 

handled, and the conditions for handling this material, to be sure they 

meet requirements. Check for any other imported biologics on the 

licensed premises. Biologics exported from the United States may only be 

returned under a permit for research and evaluation. [Reference: 9 CFR 

104.4]

c. Administrative Inspection Review

i. Licensees/permittees compare information on file regarding the firm's 

U.S. Veterinary Biologics Establishment License for the establishment, and 

if applicable, the sites. [Reference: 9 CFR 102.1 or 104.1]

ii. Activity of each licensed product, including conditional licenses

1. If a product is not being produced, determine the last date of 

production. The firm may wish to voluntarily return inactive product 

licenses for which they no longer have the equipment, facilities, 

and/or expertise to prepare to APHIS for termination. [Reference: 9 

CFR 105.4]
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

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2. Review for terminated conditional licenses [Reference: 9 CFR 

102.6(a)] 

2) Personnel 

a. Audit

i. Request a current copy of the firm’s organizational chart or obtain 

information on official lines of responsibility within the firm. 

1. Review the relationships between production, testing, marketing, and 

quality assurance. The responsible managers of production and quality 

control must be independent from each other.

2. Review spans of responsibility to ensure they are not so extensive as 

to present a risk to quality.

3. Review gaps or unexplained overlaps in personnel responsibility. 

Senior management has the ultimate responsibility to ensure 

compliance with the regulations. 

ii. Review the firm's process of determining who should have an APHIS Form 

2007 on file with CVB and the system used to maintain the listing. Identify 

the person responsible for periodically reviewing the APHIS Form 2007 

file. [Reference: 9 CFR 114.7(a)]

iii. Review training records for essential functions conducted regarding 

licensed/permitted products. [Reference: 9 CFR 114.7(b and c)]

1. All personnel (including those concerned with cleaning and 

maintenance) employed in the areas where products are 

manufactured should be given training in and information on 

microbiology, hygiene, and biosafety. They should receive additional 

training specific to the product with which they work. [Reference: 9 

CFR 114.7(c)]

2. Personnel working in areas where products are manufactured and 

tested should receive training and periodic retraining specific to their 

duties and the products manufactured. [Reference: 9 CFR 114.7(b 

and c)]

b. Observations

i. Determine if personnel designated as the official liaison and alternate 

liaisons, if applicable, are knowledgeable about the day-to-day activities at 
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

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the firm and in a position to make agreements with APHIS. [Reference: 9 

CFR 114.7(a)]

ii. Observe if employees in key positions have APHIS Form 2007s on file at 

CVB. Observe if employees follow lines of responsibility as shown on the 

organizational chart or as explained by management. See Veterinary 

Services (VS) Memorandum 800.63, Personnel at Licensed Establishments, 

for additional guidance. [Reference: 9 CFR 114.7(a)]

iii. Observe operations to determine if employees, in general, are adequately 

trained and supervised so as to be competent in good laboratory 

techniques and preparation of veterinary biological products. Be aware of 

personnel health conditions that might affect the product. [Reference: 9 

CFR 114.7(b)]

iv. Observe if there is an adequate number of personnel with necessary 

qualifications and practical experience available for the functions being 

performed. 

v. Determine if adequate measures are taken to prevent breaches in 

biocontainment or prevention of cross contamination. This may include,

but is not limited to, the use of personal protective equipment, change of 

clothes, and/or showering before leaving the production area. [Reference: 

9 CFR 114.7(c)(1)]

c. Administrative Inspection Review

i. Review list of personnel submitted on APHIS Forms 2007s on file with CVB. 

[Reference: 9 CFR 114.7(a)]

1. Review for any key changes in personnel and their responsibilities. 

2. Review for deletions, additions, or job changes. 

3. Confirm the names of the official liaison, alternates, and site contacts. 

ii. Personnel responsible for production and quality control should have an 

adequate background in relevant scientific discipline, together with 

sufficient practical experience to enable them to perform their duties. 

[Reference: 9 CFR 114.7(b)]

3) Facilities [Premises] 

a. Audit
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

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i. Inspect the premises and compare with the facility documents. See VS 

Memorandum 800.78, Preparation and Submission of Facilities 

Documents, for additional guidance. [Reference: 9 CFR 108.1]

1. Dedicated facilities may be required for manufacturing when risks 

cannot be adequately controlled by operational or technical measures.

2. Premises should be laid out in such a way as to allow production to 

take place in areas that are connected in a logical order, corresponding 

to the sequence of the operations and to the requisite cleanliness 

levels. [Reference: 9 CFR 108.8(b)]

ii. When comparing facilities with the filed facility documents, look for 

evidence of unreported remodeling, new stationary equipment, relocated 

key items, and other discrepancies. [Reference: 9 CFR 108.6(a)]

iii. Confirm that legends showing special-use facilities (such as a public 

diagnostic clinic, diagnostic facilities, separate and apart research areas, 

export-only products, pharmaceutics production, and FDA Export Reform 

and Enhancement Act production) are correct. Determine the location and 

adequacy of isolation facilities for incoming animals, if required. 

[Reference: 9 CFR 108.8(c), 117.3(a), 117.3(e)]

iv. Evaluate the site’s qualification processes for facilities, equipment, and 

utilities. Determine if the qualification and validation principles 

incorporate the critical process parameters and critical quality attributes 

needed for the production of veterinary biological products. [Reference: 9 

CFR 102.4(a)]

b. Observations

i. Verify the premises design, as listed in the blueprint documents, is actually 

being operated in compliance with the information on file. Processes must 

have adequate and appropriate isolation for each product to prevent 

cross-contamination from other products. Evaluate operations for any 

possible adverse effect on the product. [Reference: 9 CFR 108.8(b)]

1. Ensure other operations where live biological agents are handled, 

including organisms used in quality control, are appropriate, 

contained, and separated if production is operated in the same 

building. The measures used to prevent cross-contamination should be 

commensurate with the risks. [Reference: 9 CFR 108.8(c)]
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

10 | Page

a) Live biological agents should be handled in rooms or 

compartments to contain the agent. [Reference: 9 CFR 108.8(c)]

b) Ensure authorized diagnostic facilities at the licensed

establishment follow safeguards to mitigate the risks of 

contamination with pathogenic organisms. [Reference: 9 CFR 

117.3(e)]

2. Observe traffic patterns through the production area. Prevention of 

cross-contamination by personnel should be achieved by a set of 

measures and procedures to eliminate risk. This may include the use of 

air locks for personnel and equipment. Observe enforcement of 

movement restrictions. Restricted areas should be posted as such. 

[Reference: 9 CFR 108.8(b)]

3. Animal facilities should be well isolated from other areas, with 

separate entrances and air handling. [Reference: 9 CFR 117.1(b)]

ii. Observe that premises are carefully maintained; the material, 

construction, and finish of all areas related to the production of biological 

products or ingredients of biological products can be thoroughly cleaned. 

[Reference: 9 CFR 108.8(a)]

1. Walls, floors, and ceilings in areas where product is exposed must be 

smooth and free of cracks or open joints.

2. Pipework, light fittings, ventilation points, and other services should be 

designed to avoid recesses which are difficult to clean. 

iii. Observe the adequacy of the working and in-process storage space to 

permit the orderly and logical positioning of equipment and materials so 

as to minimize the risk of errors between different products, antigens, 

and/or components; to avoid cross contamination; and mitigate the risk of 

omission or wrong application of any manufacturing or control steps. 

[Reference: 9 CFR 108.8(b)]

iv. Ensure repairs, maintenance, or remodeling operations do not present a 

hazard to the quality of products. [Reference: 9 CFR 108.6]

v. Verify lighting is appropriate and such that it does not adversely affect, 

either directly or indirectly, the preparation, testing, storage of product, or 

accurate functioning of equipment. [Reference: 9 CFR 108.4(g)]
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

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vi. Verify an adequate supply of hot and cold water and ensure efficient 

drainage and plumbing systems for production and testing purposes.

Ensure drains are properly installed with approved traps and vents and are 

functioning as expected. Open channels should be avoided where 

possible, but if needed, they should be shallow to facilitate cleaning and 

disinfection. [Reference: 9 CFR 108.8(e) and (f)]

vii. Verify the heating, ventilation, and air conditioning systems are sufficient 

to adequately address issues of biocontainment and mitigate crosscontamination for the protection of products and personnel. [Reference: 9 

CFR 108.8(d)]

viii. Verify that dressing rooms, toilet facilities, and lavatory accommodations 

are appropriately placed, sufficient in number, and separated from 

production. Soap, towels, and hot water should be available. [Reference: 9 

CFR 108.9]

ix. Verify adequate biosafety measures are taken to prevent infection of 

personnel working with zoonotic agents. [Reference: 9 CFR 108.8(c) and 

(d)]

c. Administrative Inspection Reviews – not applicable to this category unless 

related to specialized questions during the annual review.

4) Equipment 

a. Audits

i. Identify equipment and environmental rooms used in production, 

testing, and storage of product. The equipment should be designed, 

located, and maintained to suit the intended purpose. [Reference: 9 CFR 

108.4(f)]

1. Verify that the location of equipment matches the code designated 

in the blueprint legends. 

2. Confirm the unique identity of equipment through production 

records, maintenance logs, and operation as intended by the 

manufacturer of the equipment. Repairs and maintenance 

operations should not present any hazard to the quality of the 

products.
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

12 | Page

3. Review the records of operation of specialized equipment, 

determine if the equipment is functioning properly, and ensure 

recordkeeping is in compliance.

ii. Verify equipment is cleaned and sterilized according to detailed, written 

procedures. Determine if sufficient records are maintained. [Reference: 

9 CFR 116.4]

iii. Review records regarding the calibration of equipment at defined 

intervals. 

1. Equipment/instrument/device calibrations should be performed 

using standards traceable to certified standards from organizations 

such as the National Institute of Standards and Technology if 

existing. 

2. The results of the calibration must be within the specified limits by 

comparison to the traceable standard. 

3. The calibrated measurement should be within the defined set of 

operating parameters, established under specific conditions for use 

during production and testing. 

iv. Determine what system is used and what records are kept by the firm to 

ensure that automatically controlled equipment is operating properly. If 

the firm has an exemption from having automatic recorders on 

sterilizers, determine if the records kept meet the provisions of 

regulations. [Reference: 9 CFR 109.2]

b. Observations

i. Look for equipment or compartments not shown on the blueprint 

and/or the blueprint legend. Determine if they are being used in 

production, testing, or storage of product and if the equipment or 

compartment is being used and maintained in compliance with the 

regulations and manufacturer’s recommendations. [Reference: 9 CFR 

108.5(b)(2)] 

ii. Observe the operation of equipment and compartments and determine 

if they are being operated properly. Production equipment should not 

present any hazards to products. If equipment is calibrated, the 

appropriate range and precision should be available for the operator.
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

13 | Page

iii. Determine if each piece of equipment is uniquely identified so the use of 

the equipment may be adequately documented and traceable in the 

manufacturing records when used in production. 

iv. Fixed pipework should be clearly labelled to indicate the contents and, 

where applicable, the direction of flow.

v. Assure that all equipment is being sterilized according to applicable 

requirements. [Reference: 9 CFR 109.1]

1. Exemptions to the regulations must be on file with CVB. Confirm 

equipment exempted from sterilization requirements listed in the 

regulations is being treated as allowed for in the exemption on file 

with CVB. See VS Memorandum 800.78, Preparation and Submission 

of Facilities Documents, for additional guidance on submitting an 

exemption.

2. Observe equipment design, it should be easily and thoroughly 

cleaned. 

c. Administrative Inspection Reviews – not applicable to this category unless 

related to specialized questions during the annual review.

5) Sanitation 

a. Audits

i. Audit the firm's records to ensure that sanitizing is done at the 

appropriate time and place, and with the appropriate chemicals, as 

specified in the facility’s blueprint legends. 

ii. Determine if the chemicals used for sanitation are appropriate for the 

microorganisms in each room.

iii. Ensure adequate biosecurity measures are in place to prevent biological 

agents being taken outside the manufacturing plant by personnel acting as 

a carrier. [Reference: 9 CFR 114.7(c)(1)]

b. Observations

i. The manufacturing environment is operated in such a way as to present 

minimal risk of causing contamination of materials or product. [Reference: 

9 CFR 108.8(b)] 
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

14 | Page

1. Notice if the outside premises are properly drained, clean, and free of 

accumulated trash or construction debris. [Reference: 9 CFR 

108.10(a)] 

2. Note whether an adequate effort is being made to control vermin, 

especially in animal quarters. [Reference: 9 CFR 108.10(c)]

3. Observe for clutter inside the premises. Determine if the clutter 

affects product quality. Check for accumulation of unnecessary 

materials, particularly in halls, production rooms, and coolers.

ii. Determine if waste disposal methods are in accordance with the 

applicable regulations. See VS Memorandum 800.56, Disposal of 

Unsatisfactory and Undesirable Materials, for additional guidance. 

[Reference: 9 CFR 114.15]

iii. Every person entering the manufacturing areas should wear protective 

garments as appropriate to the operations being carried out. Note if 

special clothing requirement areas are posted and requirements enforced. 

[Reference: 9 CFR 114.7(c)(1)]

iv. Watch for unsanitary practices by employees, such as eating, drinking, 

chewing, smoking, or storage of food, drink, smoking materials, or 

personal medication in the production areas. [Reference: 9 CFR 

114.7(c)(2)]

v. Good aseptic techniques should be used to prevent direct contact with 

the product. Appropriate personal protective equipment must be used to 

avoid direct contact with the operator’s hands and the exposed product, 

as well as with any part of the equipment that comes into contact with the 

products. 

c. Administrative Inspection Reviews – not applicable to this category unless 

related to specialized questions during the annual review.

6) Prelicensing - Products Pending Licensure 

a. Audits

i. Examine records to confirm that the firm has obtained permission from 

CVB-Program, Evaluation, and Licensing (PEL) for any research conducted 

in production facilities with organisms, antigens, or fraction not already 

approved for a licensed product. Determine impact to licensed/permitted 

product regarding the preparation of experimental product and review 
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

15 | Page

mitigating steps implemented by the firm or required by CVB. Confirm 

restrictions or conditions required by PEL were met. See VS Memorandum 

800.64, Preparation of Experimental Products at Licensed Establishments, 

for additional guidance. [Reference: 9 CFR 103.1]

ii. Verify that the Seed material is adequately identified and accounted for. 

iii. Review records for proper disposal of animals used in the preparation or 

testing of experimental products. [Reference: 9 CFR 117.6]

iv. Differentiate between research being conducted using microorganisms 

related to currently licensed products and work with new microorganisms 

not related to licensed products. Complete records are required for both, 

but fewer restrictions may be required for microorganisms related to 

currently licensed products. [Reference: 9 CFR 116.1(a)]

v. Review field trial records for compliance with special restrictions and 

requirements. Account for product prepared and distributed for field 

trials. Determine if the product was prepared in accordance with the 

Outline of Production on file. Determine if all responses were reported to 

PEL. Determine if the detailed records support the summaries sent to PEL. 

[Reference: 9 CFR 103.3]

vi. Review the minutes of Institutional Biosafety Committee meetings. 

Determine if appropriate members have been appointed. Determine if all 

biotechnology work and especially recombinant product work are being 

addressed and if appropriate policy and procedures have been 

established.

vii. Determine if prelicensing serials were prepared in production facilities and 

tested on licensed premises. [Reference: 9 CFR 102.5(c)(1)]

viii. Determine if the expiration dating on newly licensed products has been 

confirmed, submitted to PEL for review, and documented in the Outline of 

Production. [Reference: 9 CFR 114.14]

b. Observations

i. Determine if the separation of personnel, supplies, and equipment 

between research and production is adequate. 

ii. Observe the in-house controls on movement of personnel, supplies, and 

equipment and the airflow control between research, production, and 

testing areas.
U.S. DEPARTMENT OF AGRICULTURE 

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Veterinary Services 

VS Memorandum (VSM) 800.91 

 

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iii. Check for production-related testing in research areas.

iv. Check methods for disposing of research material. [Reference: 9 CFR 

114.15]

v. Observe specific research or prelicensing activities as requested by PEL. 

[Reference: 9 CFR 103.1]

vi. Observe if employees are following biosafety policies. 

vii. Determine if biosafety policies are adequate.

c. Administrative Inspection Review - Licensees/permittees compare 

information on file regarding the status of prelicensing projects related to U.S. 

Veterinary Biologics Product License applications. [Reference: 9 CFR 102.5 or 

104.5]

7) Seeds and Cells 

a. Audits

i. Confirm the Master Seeds and Master Cell Stocks being used in 

production are the same as those listed in the corresponding Outline of 

Production. [Reference: 9 CFR 114.5]

ii. Confirm the Master Seed and Master Cell Stock were prepared and tested 

according to the regulations and Outlines of Production. [Reference: 9 CFR 

116.1(a)(1)]

iii. The number of passages for seed and cell stocks must be consistent with 

the information listed in the Outlines of Production. [Reference: 9 CFR 

114.5]

1. Review each passage level of seed and cell stock used in the 

preparation of product.

a) Accountability of use (including amount discarded).

b) Exact identification of material used.

c) Traceability from production lot back to the master stock.

2. Records must be complete and reflect compliance with the regulations 

and corresponding Outline of Production. 
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Marketing and Regulatory Programs

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Veterinary Services 

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iv. Each storage container should be adequately sealed, clearly labeled, and 

kept at an appropriate temperature. Determine if the system of 

identification is adequate to ensure proper seed/cell stock has been used. 

[References: 9 CFR 114.4 and 114.11]

1. Verify the identity of all working and production seeds and cell stocks 

and trace their lineage back to the Master Seeds and Master Cell 

Stocks identified in the Outline of Production. [Reference: 9 CFR 114.5]

2. Verify that the passage levels of the Master Seeds, Working Seeds, 

Production Seeds, and Master Cell Stocks, including working and 

production cell stocks, used in producing the product serial are all 

acceptable based on the corresponding passage levels used in 

developing the prelicense data and specified in the Outline of 

Production.

v. Determine where Master Seeds and Master Cell Stocks are maintained, 

handled, and produced. These materials have very specific requirements, 

which should be consistent with information in the blueprint legends. 

[Reference: 9 CFR 114.5]

vi. Review records of Master Cell Stocks for batches of primary cells to 

determine their source, if the source animal was free of disease, and if 

acquisition was according to the regulations. Determine if batches of 

primary cells have been adequately tested. [Reference: 9 CFR 113.53]

vii. Review Master Seed production and testing records. Review 

immunogenicity test records. Determine if the bench records for each 

serial of product are complete and clearly trace to the Master Seed. 

[Reference: 9 CFR 116.1(a)]

viii. Review records for ingredients of animal origin to determine compliance 

with the regulations. [Reference: 9 CFR 113.53]

b. Observations

i. Observe any production or testing procedures in progress for compliance 

with the Outline of Production or regulations. Note if the seeds are 

monitored regularly for virulence, how they are maintained, how 

frequently they are passed, how they are stored, how much current 

inventory exists, etc.

ii. Determine where Master Seed, Working Seed, and Production Seed are 

prepared. Only Master Seed may be prepared in separate and apart 
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

18 | Page

research facilities; Working Seed and Production Seed must be prepared 

on licensed premises in acceptable facilities.

iii. Determine if the methods of maintenance, storage, and inventory of 

Master Seeds and Master Cell Stocks comply with the regulations and 

corresponding Outline of Production.

iv. Check if there are separate storage facilities for virulent or dangerous 

microorganisms and if there is a possible impact on licensed product 

quality.

c. Administrative Inspection Reviews

i. Confirm identity of the Master Cell Stock and/or Master Seed as listed. 

[Reference: 9 CFR 114.5]. 

ii. Confirm inventory status of each cell stock and seed. 

8) Production (inoculation through batching) 

a. Audits

i. Records must be detailed enough to provide a complete accountability of 

the production process. [Reference: 9 CFR 116.1(a)(1)]

1. Review records of production procedures for data integrity, including,

but not limited to, accountability and identification of each step. 

a) Tracing serials and production lots from raw ingredients to filling.

b) Checks on yields and reconciliation of quantities should be carried 

out as needed to ensure there are no discrepancies outside the 

acceptable limits. 

2. Verify that records are complete, and that each critical procedure is 

listed in the Outline of Production. 

3. Review records for data integrity. If recordkeeping deficiencies are 

found, determine if they apply only to that serial or lot, or if they are 

consistent deficiencies for that product, group of products, or all 

products. 

ii. Determine if the serial or production lot has been prepared according to 

the version of the Outline of Production in effect when the lot was 

presented to CVB for market release (this includes sample submission); 
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

19 | Page

compare the date of production with the date on the outline used for 

reference. [Reference: 9 CFR 114.2(a)]

1. Check to see that each step listed in the outline is documented in the 

records. 

2. Review the records to determine if all critical steps are described in 

the Outline of Production. 

3. If deviations from the outline are noted, determine if they apply only 

to that serial or lot, that product, a group of products, or all products.

iii. Determine if the manufacturer’s recordkeeping system provides for the 

unique identification, tracking, and recording of each ingredient and if 

safeguards are in place to prevent errors in the preparation of the 

product. [Reference: 9 CFR 114.4]

iv. Determine how serial numbers are assigned and what system is used.

v. Production operations must follow clearly defined steps as listed in the 

Outline of Production. The Outline of Production must contain all critical 

procedures in production to be considered accurate and sufficient. 

[Reference: 9 CFR 114.8(d)]

1. Determine how annual outline reviews are done and by whom. The 

process should be documented.

2. Determine frequency of reviews and if the reviews are sufficient. 

b. Observations

i. Evaluate any production procedure in progress for compliance with the 

most recent Outline of Production and facility documents. [Reference: 9 

CFR 102.5(c)(1)]

ii. Determine if the identity of in-process material is maintained. Ensure 

suitable tags or labels are used to adequately identify all ingredients used 

in the preparation of biological products. Note the manner of 

identification used and the consistency of its use (e.g., color coding, lot 

numbers, product name). [Reference: 9 CFR 114.4]

iii. Observe whether proper laboratory techniques and sterile practices are 

followed by laboratory personnel where required. [Reference: 9 CFR 

114.7(c)]
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

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1. Operations on different products should not be carried out 

simultaneously or consecutively in the same room unless there is no 

risk of mix-up or cross contamination. 

iv. Check that the equipment and workstations/rooms are cleared of previous 

products, documents, and materials prior to use for current production 

step. 

v. Observe the preparation of equipment, media, and other ancillary 

procedures in the service area for compliance with the regulations and 

applicable special outlines. [Reference: 9 CFR 113.50]

vi. Note any production procedures that differ from the Outline of 

Production and evaluate the effect on the product. Even though the 

procedures may be within limits of acceptable laboratory practice or are 

intended to improve the product, variations are not allowed unless the 

outline is changed to reflect the variations. Determine if approved outlines 

are available to be used, and are used by, line supervisors. [Reference: 9 

CFR 114.2(a)]

vii. Look for any procedures that may adversely affect the product. 

viii. Verify open circuit operations involving products or components not 

subsequently sterilized are carried out within a laminar air workstation 

within the production room or by another acceptable method, such as the 

use of quick-connect devices. [Reference: 108.8(d)]

c. Administrative Inspection Reviews – note that Special Outlines may be 

applicable to other categories of inspection, such as testing. 

i. Confirm the file date of the most current Outline of Production/Special 

Outline [Reference: 9 CFR 114.8(e)(1)]. 

ii. Review the date of the last annual review. [Reference: 114.8(d)]

9) Final Production (filling to labeling and packaging) 

a. Audits

i. Review filling records for recorded losses or gains, fill checks, and filling 

problems. Determine compliance with the fill ranges as filed in the 

Outline of Production. Determine how overfilled or underfilled vials are 

handled and if the firm has a written policy covering this. [Reference: 9 

CFR 116.1(a)(1)]
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

21 | Page

ii. Determine the lyophilization requirements for each product. Review 

lyophilization records of selected serials for compliance and 

recordkeeping practices. Determine if temperature probe readings are 

identified on the recording charts.

iii. Determine if all reprocessing was authorized. Changes to composition of 

completed liquid product, prior to filling and/or labeling, can only be 

done when provided for in the Outline of Production or when authorized 

by CVB. [Reference: 9 CFR 114.18]

iv. Review records of controlled freezing to determine if procedures follow 

the Outline of Production for products where this is critical, such as 

Marek's Disease Vaccine.

v. Determine if losses incurred through breakage, loss of vacuum, etc., are 

recorded in the serial records. [Reference: 9 CFR 116.1(a)(1)]

vi. Determine if the firm can substantiate the container label, the carton 

label, and the enclosure used were appropriate for the final use product. 

[Reference: 9 CFR 116.3(b)]

vii. Determine if subserials are being appropriately identified when further 

processed at different times or under different conditions, such as 

lyophilization in different dryers or at different times. [Reference: 9 CFR 

101.3(i)]

viii. Review the records to determine if all critical processes are described in 

the Outline of Production. [Reference: 9 CFR 114.8(d)]

ix. Review records for data integrity. [Reference: 9 CFR 116.1(a)]

b. Observations

i. Observe and evaluate actual filling procedures, including aseptic 

technique, fill checks, proper mixing during fill, appropriate temperature 

control, and maintenance of concurrent records. Determine if employees 

adhere to the specifications listed in the Outline of Production and how to 

handle unacceptably filled vials. 

ii. Confirm lyophilization procedures. Determine if placement of probes is 

adequate. Note stoppering devices. 

iii. Note in-house procedures for vial and label inspection, sampling, 

identification of unlabeled vials, and how product is controlled until 

released. Ensure suitable tags or labels are used to adequately identify all 
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

22 | Page

ingredients used in the preparation of biological products. [Reference: 9 

CFR 114.4] 

iv. Review handling of diluent, how and where it is stored, and how it is 

accounted for. See VS Memorandum 800.74, Preparation and Distribution 

of Sterile Diluents, for additional guidance. [Reference: 9 CFR 113.54]

v. Examine freezing procedures. Determine the time interval from filling to 

start of freezing and the rate at which product temperature is lowered is 

in accordance with the Outline of Production.

vi. Observe several selected serials for product uniformity, color, volume, 

texture, opacity, labeling, packaging, serial number readability, and 

expiration date. Check labels to ensure they have not rubbed off and are 

legible. [Reference: 9 CFR 112.1(d)]

vii. Determine if products other than biologics are filled, packaged, or labeled 

on the licensed premises. Determine if adequate separation of licensed 

serials of product and unlicensed product is maintained during filling, 

packaging, and labeling. 

viii. Review records for any process deviations, including detailed summary of 

deviation, root cause analysis, investigation report, corrective and 

preventative actions (CAPA), and the review process to determine CAPA 

effectiveness. See VS Memoranda 800.210, Manufacturing Deviations 

Identified prior to Marketing Release, and VS Memoranda 800.57, Market 

Suspensions and Post Marketing Temperature Deviations, for additional 

guidance. [Reference: 9 CFR 114.2(a)]

c. Administrative Inspection Reviews – not applicable to this category unless 

related to specialized questions during the annual review.

10) Labels and Packaging 

a. Audits

i. Review the files of the firm's label inventories for inactive, expired, 

superseded, or obsolete labels. Obsolete material should be destroyed,

and the disposal recorded. [Reference: 9 CFR 116.3(a)]

ii. Review the process regarding expiration date determinations. Ensure the 

process accounts for compliance with the regulations and the applicable 

Outline of Production. Include the process used for relabeling, for 
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

23 | Page

example, when an extension of dating is approved by CVB. [Reference: 9 

CFR 114.13]

iii. Review the label control process for new and revised labels. Determine if 

the process is in control and can ensure compliance with the regulations. 

[Reference: 9 CFR 112.1(a)]

iv. Compare the label stock against the CVB filed label for accuracy. 

[Reference: 9 CFR 112.1(b)]

1. Printed labeling materials are considered critical to the conformity of 

the product. Pay special attention to the safe and secured storage of 

these materials. 

2. Ensure that the firm maintains accountability for all labels printed for 

use on licensed products. Review inventory records and compare with 

actual inventories. Determine accountability of damaged and 

destroyed labels. [Reference: 9 CFR 116.3(b)] 

v. Review the method used to ensure the correct label, with the correct 

serial number and expiration date, were used for each labeling and 

packaging event. [Reference: 9 CFR 112.1(b)] 

vi. If product is moved from the required storage temperature and allowed to 

acclimate to room temperature prior to labeling, evaluate the process 

used and if the impact to the final product has been determined. 

[Reference: 9 CFR 114.11]

b. Observations

i. Review the process used to ensure all labels and labeling material printed 

is accounted for and the inventory is accurate. This should include the 

amount used, destroyed, and returned to stock to provide for adequate 

reconciliation. [Reference: 9 CFR 116.3(b)]

ii. Determine serial numbers and expiration dates printed on labeling 

material are legible and remain legible throughout the dating period. 

[Reference: 9 CFR 112.1(d)]

iii. Observe the process in which serial numbers and expiration dates are 

inspected and verified for accuracy. [Reference: 9 CFR 101.3(h) and 

101.4(f)]

iv. If multiple labeling or packaging events occur at the same time, pay 

attention to the controls in place to mitigate the risk of mix-ups or 
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

24 | Page

substitutions. Different products should not be labeled or packaged in 

close proximity unless there is a physical segregation of processes and 

materials. 

v. Observe steps taken prior to and during labeling or packaging events

1. Operations should ensure the work area, line, printing machine, and 

other equipment are clean and free of previously used material. A 

line-clearance should be performed in accordance with a written 

procedure (e.g. a check list). 

2. Labeling and/or packaging lines should be identified by product and 

lot numbers. 

3. Materials should be checked upon delivery to the labeling/packaging 

department for quantity and identity. 

vi. Observe how long serials are out of the cooler during finishing procedures.

Determine if the firm has established maximum time product can be out 

of the cooler and can substantiate effects to quality of the product. 

Determine if this time may be detrimental to the product, including the 

lifetime of the product. Establish how they record/monitor out of cooler 

time. [Reference: 9 CFR 114.11]

c. Administrative Inspection Reviews

i. Confirm listing of active filed labels is complete. [Reference: 9 CFR 

116.3(a)]. 

ii. Review use of temporary or extended use labels for compliance 

requirements applied. [Reference: 9 CFR 112.1(b)] 

11) Testing (Quality Control) 

a. Audits

i. Review laboratory records for all testing performed, especially testing 

required by the Outline of Production or regulations. This includes 

selected tests for ingredients/raw materials, bulk lots, serials, Seeds, Cell 

Stocks, and diluents. [Reference: 9 CFR 113.5(a)]

1. Determine if all critical steps of the test were documented. The 

records should include the following:

a) Test material and dosage (as applicable).
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

25 | Page

b) Testing dates; initiation, observations, conclusion.

c) Test results including calculations. Observations of results must be 

clearly described and documented.

d) Each step is authenticated by the individual performing that step.

e) Reference to the equipment used.

2. Results of quality parameters, including but not limited to references 

and controls, should be trended and checked for consistency with the 

expected results.

3. Review test records for data integrity. 

ii. Note if tests contain the proper controls and if critical components, 

reagents, and equipment are monitored for quality before and/or during 

the test. [Reference: 9 CFR 113.2(b)(c)(d)]

iii. Make sure all tests summarized on APHIS Form 2008 reports are 

supported by review of the testing bench records. See VS Memorandum 

800.53, Release of Biological Products, for additional guidance. 

[Reference: 9 CFR 116.7]

iv. Review any tests conducted by the firm that are not reported on the 

APHIS Form 2008. Determine if the results of such tests may indicate an 

issue with the purity, safety, or potency of the product and require special 

attention. Note: The firm may test product in accordance with 

requirements from an importing country. Test results that raise questions 

regarding the purity, safety, potency, or efficacy of a serial should be 

reported to CVB in accordance with VS Memorandum 800.57, Market 

Suspensions and Post Marketing Temperature Deviations. [Reference: 9 

CFR 116.5(b)]

v. Evaluate whether retests are conducted according to regulations and/or 

the Outline of Production. [Reference: 9 CFR 113.5(d)]

vi. Check to see that the blueprint legend lists those microorganisms that are 

not named in the Outline of Production but that are necessary for testing 

purposes, such as organisms used for growth promotion testing or 

controls. [Reference: 9 CFR 108.5(b)(1)]

vii. If the firm is authorized to use unlicensed facilities for potency testing in 

the Outline of Production, review testing records from the contract testing 
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

26 | Page

facility. Also review licensee’s audit plan of the contract testing facility to 

ensure ongoing quality control. See VS Memorandum 800.115, Potency 

and Safety Testing by Unlicensed Facilities, for additional guidance. 

viii. If the firm was given an animal safety exemption, review the product file 

for nonconformance to the Outline of Production and impacts to product. 

See VS Memorandum 800.116, Target Animal Safety Testing Exemption, 

for additional guidance. 

b. Observations

i. Observe testing procedures to determine if they are being performed in 

compliance with the Outline of Production and the regulations. 

[Reference: 9 CFR 113.5(a)]

ii. Observe testing procedures to determine if the firm is using proper 

laboratory technique along with proper recordkeeping. [Reference: 9 CFR 

113.5(c)]

iii. Observe if proper testing controls are used and recorded. [Reference: 9 

CFR 113.5(c)]

c. Administrative Inspection Reviews

i. Confirm identity of the listed references used for potency testing of final 

product. [Reference: 9 CFR 113.8(c)].

ii. Review expiration dating of each reference to confirm reference was 

within dating when used for release testing. [Reference: 9 CFR 113.8(d)]

iii. Review lists of incomplete APHIS Form 2008 submissions (2008 Forms 

submitted without samples or samples submitted without 2008 Forms). 

[Reference: 9 CFR 116.7]

12) Animals 

a. Audits

i. Determine if the firm is a registered research facility or a licensed animal 

dealer under the Animal Welfare Act. Record the registration or license 

numbers for reference. Review the last APHIS Animal Care inspection 

report to see if there were any deficiencies. Determine if they have been 

corrected.
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

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ii. For animals used in production and testing, review procurement and test 

records for completeness, accuracy, and compliance with requirements in 

the Outline of Production and Animal Welfare regulations. Where 

required, ensure that proper health certificates have been issued and filed 

(e.g., equine infectious anemia testing records for horses used in 

production or testing). [Reference: 9 CFR 116.6, 117.3, 117.4, and 117.6]

iii. Review records for data integrity. Determine the completeness of records 

for animals used in production or testing and examine these records when 

inspecting according to the production and testing categories listed in this 

memorandum. [Reference: 9 CFR 116.6]

iv. Determine if the firm keeps accurate records to identify animals and trace 

their final disposition. Certain animals must be quarantined before being 

removed from the premises and when moved must be accompanied by 

the appropriate forms. [Reference: 9 CFR 117.5 and 117.6]

b. Observations

i. Check for compliance with requirements of the Animal Welfare Act. 

Animals not subject to the Act should also be cared for in the spirit of the 

Act. Report items needing immediate attention to the Animal Care Sector 

Supervisor at once.

ii. Note whether animals are adequately identified. [Reference: 9 CFR 

117.3(c)]

iii. Determine if a firm has necropsy facilities for animals used for production 

and test purposes.

iv. Determine if the admitting veterinarian examines the animals before 

admittance or in a separate quarantine area on premises. Note if another 

employee examines the animals for the veterinarian. [Reference: 9 CFR 

117.3(a)]

v. Determine whether there is any preconditioning or treatment of animals 

that might adversely affect testing or production. [Reference: 9 CFR 

117.4(c)]

c. Administrative Inspection Reviews – not applicable to this category unless 

related to specialized questions during the annual review.

13) Distribution 
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

28 | Page

a. Audits

i. Evaluate the method used by the licensee/permittee to reconcile 

estimated and actual inventories prior to marketing release. [Reference: 9 

CFR 116.2]

ii. Determine whether distribution records are adequate for inventory 

control.

iii. Determine if the firm’s records are such that the firm could carry out a 

total stop sale or recall down to user level should it become necessary. 

[Reference: 9 CFR 116.5(a)]

iv. Review the written procedure for product recalls or stop sale events. 

Ensure it covers all levels and includes communication plan with CVB. 

[Reference: 9 CFR 105.3]

1. The process should be regularly reviewed and updated as needed. The 

effectiveness of the process should be evaluated periodically to 

confirm it is robust and fit for use. 

2. Review documentation of any recent product recall or stop sale. 

Determine if the actions taken were appropriate and in accord with 

the regulations. See VS Memo 800.57, Market Suspensions and Post 

Marketing Temperature Deviations, for additional guidance.

v. Determine control processes for distribution of restricted products.

[Reference: 9 CFR 102.5(d)]

vi. Review distribution records for data integrity. [Reference: 9 CFR 116.2]

b. Observations

i. Evaluate the system(s) of control and identification on pre- and postrelease serials used to prevent inadvertent distribution of unreleased 

serials. [Reference: 9 CFR 113.6]

1. Storage areas should be adequately designed and operated to allow 

orderly storage of pre- and post-release serials.

2. Segregated areas should be provided for material and products that 

are in a quarantine, rejected, returned, or recalled status. 
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

29 | Page

3. If quarantine status is ensured by storage in separate areas, these 

areas must be clearly marked, and access restricted to authorized 

personnel. 

ii. Determine if cooler space is adequate for licensed products at the normal 

level of production. The storage area should be clean and dry. Confirm the 

storage temperature is maintained within acceptable temperature limits. 

[Reference: 9 CFR 114.11] 

iii. Review the release system with the firm to ensure adequate 

documentation and control. Verify who is designated to receive marketing 

release authorizations from Inspection and Compliance. [Reference: 9 CFR 

113.6]

iv. Compare the marketable inventory as reported on APHIS Form 2008 with 

the actual inventory. Determine if the firm uses a standard inventory 

variance and if this variance is reasonable. Any changes in inventory 

beyond the firm’s variance standard or in the absence of a firm standard 

should be reviewed further. [Reference: 9 CFR 116.2]

v. Observe coolers and warehouses for expired product, product deemed 

unacceptable for marketing, or product returned from the marketplace. 

[Reference: 9 CFR 114.15]

1. Determine how these goods are handled and final disposition. 

2. Review recordkeeping for returned goods. Determine if the firm redistributes products and if the methods are acceptable. See VS 

Memorandum 800.60, Biological Products Returned to Licensed 

Establishments, for additional guidance. [Reference: 9 CFR 114.11]

vi. Evaluate shipping methods to determine if product is always protected

against improper storage and handling. [Reference: 9 CFR 114.11]

c. Administrative Inspection Reviews – not applicable to this category unless 

related to specialized questions during the annual review.

14) Miscellaneous 

a. Audits

i. Discuss the establishment’s pharmacovigilance program with the 

responsible official and/or Consumer Compliant Contact (CCC). Evaluate 

the pharmacovigilance system used to maintain detailed records for every 
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

30 | Page

adverse event report (AER) received for biological product it produces or 

distributes. [Reference: 9 CFR 116.9]

1. Review the establishment’s written procedures describing the actions 

to be taken upon receipt of an AER for any licensed or permitted 

biological product. Ensure it includes a records retention policy of 3 

years after the date the adverse event report is received.

2. Ensure appropriately trained and experienced personnel are 

responsible for managing adverse event issues, including investigating 

these complaints. A CCC should be identified for each licensee or 

permittee and have an APHIS Form 2007 on file. 

3. Following receipt of an AER, ensure timely and proper action was 

taken if the product was found to be worthless, contaminated, 

dangerous, or harmful. [Reference: 9 CFR 116.5(b)]

ii. Review the written procedure for process deviations and/or quality 

defects, including the procedure for the root cause analysis. See VS 

Memoranda 800.210, Manufacturing Deviations Identified prior to 

Marketing Release. [Reference: 9 CFR 114.2(a) and 116.5(a)]

1. Sufficiently trained personnel and resources should be available for 

handling, assessing, investigating, and reporting out the results. 

a) The processes in place should facilitate the investigation into the 

quality of the product/process in question. 

b) Documentation should include the description of the reported 

deviation. 

c) An appropriate level of root cause analysis work should be applied 

during the investigation. In cases where the true root cause cannot 

be determined, consider identifying the most likely root cause(s) 

and address those issues. 

d) Where human error is suspected or identified as the root cause, 

this should formally be justified. Consideration should be given to 

ensure the processes and procedural or system-based errors or 

problems are not overlooked.

2. The manufacturer should have the ability to determine and implement 

risk-reducing action to mitigate the severity and probability of harm to 

the end user. Implementation of risk reducing actions should be 
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

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monitored, as new risks could be inadvertently introduced through the 

corrective and/or preventative actions. 

3. When a process deviation or quality defect is discovered or suspected 

in a lot/batch, consider checking other batches or related products to 

determine if they are also affected. The scope of the issue must be 

determined. 

4. Previous process deviations should be reviewed to determine if this is 

a recurring problem that requires attention and possibly further 

regulatory action. 

5. Implement corrective and preventative actions. Monitor and assess 

the effectiveness of such actions. 

iii. Ensure that only authorized samplers sign the APHIS Form 2020. Arrange 

to train new and current samplers as necessary. Verify the list of 

authorized samplers. See VS Memorandum 800.59, Veterinary Biological 

Product Samples, for additional guidance. [Reference: 9 CFR 113.3(a)]

iv. Verify that products found unsatisfactory by the firm were destroyed and 

reported destroyed on an APHIS Form 2008. Ensure the reason for 

destruction listed on the APHIS Form 2008 matches the 

production/testing records reviewed. Determine if the licensee/permittee 

investigated why the product was found unsatisfactory for marketing.

v. Check the blueprint legends for notation of storage location of APHIS 

reserve samples.

b. Observations

i. Inspect storage areas to verify that products reported destroyed by the 

firm are not still being retained by the firm.

ii. Inspect the quarantine area for separation and security.

iii. Observe that only authorized samplers are selecting samples for APHIS 

testing. [Reference: 9 CFR 113.3(a)]

iv. Review sampling techniques. Be sure samples collected are representative 

of the entire serial. Review the methods of authentication and verify 

compliance with the regulations. Check the method of packing samples for 

shipment. [Reference: 9 CFR 113.3(a)(1)(iv)]

v. Review APHIS Form 2020 preparation with the sampler. 
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.91 

 

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vi. Observe reserve samples for proper authentication, ensure they are made 

tamper evident, and document the chain of custody. See VS 

Memorandum 800.59, Veterinary Biological Product Samples, for 

additional guidance. [Reference: 9 CFR 113.3(e)]

vii. Determine that products "to be destroyed under APHIS supervision" have 

been properly quarantined. Observe the destruction of these products 

and report it on APHIS Form 2045. Review the inventory and accounting of 

any samples retained from unsatisfactory serials.

c. Administrative Inspection Reviews – not applicable to this category unless 

related to specialized questions during the annual review. 

7. Implementation/Applicability 

Updated policy in this memorandum is effective immediately.