Inspection Techniques and Reporting Violations Related to 

9 CFR 102.5(c)(1) and 114.8(d)

ICWI0237.04 Page 1 of 5

Author: Daniel C. Coyle

Issue Date: 26Jul18

Source Document: Title 9, Code of Federal Regulations, parts 114.8(d) and 102.5(c)(1)

BACKGROUND

When auditing records or making observations during an on-site inspection, the Biologics 

Specialist (Specialist) utilizes the filed Outline of Production, Special Outlines, and 

regulations to determine compliance. It is critical that these foundational documents be 

accurate and sufficient in detail to allow a determination of compliance and consistency 

in preparation of quality product. It is also critical that the Outlines are adhered to in 

order to manufacture a consistent quality product.

The term Outline of Production will be the reference used for both Outlines of Production 

and Special Outlines for the remainder of the document. 

REGULATIONS 

1. 9 CFR 102.5(c)(1) “Licensed biological products shall be prepared as required by the 

regulations and in accordance with a filed Outline of Production as prescribed in §§114.8 

and 114.9. No change shall be made in the preparation of a biological product without 

prior approval of the Administrator.”

During the prelicensing phase of a product, critical and essential steps in the production 

and testing process should be documented; starting with the pivotal efficacy serial 

through the consistency serials. These steps must be included in the Outline of 

Production.

9 CFR 102.5(c)(1) also requires the product to be prepared according to the regulations. 

All products prepared must be according to the regulations unless specifically exempt in 

the Outline of Production.

2. 9 CFR 114.8(d) “Each licensee shall review each Outline of Production for accuracy 

and sufficiency not less frequently than once a year. Revisions necessary to bring an 

Outline of Production into compliance with the regulations shall be submitted to Animal 

and Plant Health Inspection Service.”

The review is expected to discover any inaccuracies or insufficiencies. An Outline of 

Production is inaccurate and insufficient if critical steps are not included.

DEFINITIONS

Critical Step: An important step, process, ingredient, piece of equipment, or a decision 

point, with respect to the final outcome.
Inspection Techniques and Reporting Violations Related to 

9 CFR 102.5(c)(1) and 114.8(d)

ICWI0237.04 Page 2 of 5

Author: Daniel C. Coyle

Issue Date: 26Jul18

Source Document: Title 9, Code of Federal Regulations, parts 114.8(d) and 102.5(c)(1)

Examples of Critical Steps:

 Critical decision point – may be those that are of a Yes/No nature

o Will the preparation of product proceed, or not proceed, if this operation is not 

performed?

 Critical step in a procedure, performed consistently in the preparation of the 

product and if deleted or altered, may affect the quality of the product or shelf 

life.

Outline of Production: [9 CFR 101.3(j)]: A detailed protocol of methods of manufacture 

to be followed in the preparation of a biological product. Title 9 CFR 114.8(a): The 

Outline of Production shall be prepared as prescribed in 114.9.

Detailed Outlines of Production are expected to list all critical steps in the preparation of 

the product. Outlines of Production are required to be reviewed for accuracy and 

sufficiency.

INSPECTION TECHNIQUES RELATED TO:

1. Possible Processes to Changes to the Outline of Production

As required in 9 CFR 102.5(c)(1), “No changes shall be made in preparation of a 

biological product without prior approval of the Administrator”. 

In the majority of cases, data is required to be submitted for Center for Veterinary 

Biologics (CVB) review when a change to the Outline of Production is requested. 

Therefore, products ineligible for marketing release can be prepared outside of the 

parameters listed in the currently filed Outline of Production with the intent to submit the 

data as part of the request to make changes to the Outline of Production. 

The preparation of the products outside the parameters listed in the currently filed Outline 

of Production cannot jeopardize or risk other processes, ingredients, or products.

Review serials prepared for these situations during inspection and ensure the following 

criteria was in place:

a. The product contains CVB approved organisms/vectors/cells.

b. The serial(s) are properly controlled (quarantined) until such time CVB-Policy, 

Evaluation, and Licensing (CVB-PEL) has approved the changes to the Outline of 

Production.

i. Samples may be requested as part of this review process and can be 

submitted.

ii. The APHIS Form 2008 marked as “Eligible for Release” for the product 

cannot be submitted prior to approval of the updated Outline of Production. 
Inspection Techniques and Reporting Violations Related to 

9 CFR 102.5(c)(1) and 114.8(d)

ICWI0237.04 Page 3 of 5

Author: Daniel C. Coyle

Issue Date: 26Jul18

Source Document: Title 9, Code of Federal Regulations, parts 114.8(d) and 102.5(c)(1)

If it has been, it should be a violation and may result in an Infraction

Notification.

2. 9 CFR 102.5(c)(1)

a. If there is evidence that the product was not prepared according to the Outline of 

Production, this is likely a violation of 9 CFR 102.5(c)(1). 

b. It is important to determine whether product was prepared outside the Outline of 

Production versus not documenting the preparation appropriately.

c. Documentation must be available to substantiate that the preparation of product 

has been performed according to the Outline of Production currently on file with 

CVB. If documentation is not sufficient, this is likely a record keeping violation.

3. 9 CFR 114.8(d)

Documentation must be available to substantiate the Outline of Production has been 

reviewed for accuracy and sufficiency on a yearly basis. This means that each filed 

Outline of Production must be reviewed within the last 12 months by individuals who are 

familiar with the procedures currently used in the processes. The process and review must 

be adequately documented.

If the Outline of Production review is documented, but during the inspection there are 

findings regarding the lack of detail for critical steps or critical steps are not in the 

Outline of Production, it may be determined the review process is insufficient and the 

Outline of Production is inaccurate and insufficient.

Many establishments use manufacturing directions that usually contain more detail of the 

production process than does the Outline of Production. The Specialist needs to 

determine if there are critical steps being done and recorded that should be listed in the 

Outline of Production. If it is determined that the Outline of Production is missing critical

details, the violation is usually of the minor to less serious nature unless the violation has 

been observed during previous inspections.

While the requirements in the manufacturing directives/standard operating procedures 

(SOPs) may be more precise, the requirements, ranges, parameters listed must be within 

the requirements, ranges, or parameters detailed in the Outline of Production.

Examples of Outlines of Production that are not accurate or sufficient:

a. Manufacturing directives or SOPs that contain critical processes that are not listed 

in the Outline of Production. 

b. If the process described in the Outline of Production is ambiguous or is

interpreted differently than intended.
Inspection Techniques and Reporting Violations Related to 

9 CFR 102.5(c)(1) and 114.8(d)

ICWI0237.04 Page 4 of 5

Author: Daniel C. Coyle

Issue Date: 26Jul18

Source Document: Title 9, Code of Federal Regulations, parts 114.8(d) and 102.5(c)(1)

c. If the PEL Reviewer has changed the Outline through Pen and Ink corrections, or 

requested changes on the APHIS Form 2015, and the Establishment has not 

incorporated those changes to the Outline at the yearly review or deadline 

stipulated by the Reviewer (see PEL Manual, Work Instruction 4.1 or current 

instruction).

VIOLATION AND INSPECTION REPORT CITATION

1. Title 9 CFR 102.5(c)(1)

If the establishment is not adhering to the Outline. The risk to the product must be 

evaluated by the inspector to determine categorization of the violation (see ICSOP0105, 

Compliance Policy for Issuing Regulatory Actions) and below.

If the establishment cannot substantiate that the Outline is being complied with. This is a

violation of 9 CFR 116 if the inspector determines the step had a good probability of 

occurring. The risk to the product must be evaluated by the inspector to determine 

categorization of the violation (see ICSOP0105).

If an establishment is not preparing product according to the regulations, this is a 

violation of 102.5(c)(1). The risk to the product must be evaluated by the inspector to 

determine categorization of the violation (see ICSOP0105). 

i. Assess if the product was prepared to substantiate a change to the Outline of 

Production.

ii. If an APHIS Form 2008 has been submitted to CVB for marketing release 

purposes and the product was not prepared according to the Outline of 

Production, this is a serious violation (see ICSOP0105).

iii. If the product has been released to the market, the finding is usually a 

serious violation and if the establishment does not initiate a voluntary stop 

distribution and sale, contact the office to initiate a mandatory stop 

distribution and sale.

Violation – Name, Code, Serial, was not prepared in accordance with Outline of 

Production and (submitted APHIS Form 2008 for marketing release to CVB) or (the 

product was released to the market).

[Reference: 9 CFR 102.5(c)(1)]

Observation/Audit

Cite product and serial as well as any subsequent distribution actions.
Inspection Techniques and Reporting Violations Related to 

9 CFR 102.5(c)(1) and 114.8(d)

ICWI0237.04 Page 5 of 5

Author: Daniel C. Coyle

Issue Date: 26Jul18

Source Document: Title 9, Code of Federal Regulations, parts 114.8(d) and 102.5(c)(1)

ACTION ITEM: (Liaison) agreed to prepare product intended for marketing release 

in accordance with the approved Outline of Production immediately.

2. Title 9 CFR 114.8 (d)

If the Outline is not sufficient or accurate based on audits, documentation, or 

observations made during the inspection. The risk to the product must be evaluated by the 

inspector to determine categorization of the violation (see ICSOP0105).

Violation – The Outline of Production for Name, Code was determined to be 

inaccurate and insufficient.

[Reference: 9 CFR 114.8(d)]

Observation/Audit

Cite product and the facts pertaining to the discovery of the violation.

ACTION ITEM: (Liaison) agreed that (name of establishment) will review the 

Outline of Production for accuracy and sufficiency. The inaccuracies and/or

insufficiencies will be corrected within (timeline – dependent on the severity of the 

issue).