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CVBSOP3001.09

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United States Department of Agriculture

Center for Veterinary Biologics

Standard Operating Policy/Procedure

Reference and Reagent Review and Release 

Date: June 5, 2015

Number: CVBSOP3001.09

Supersedes: CVBSOP3001.08, March 17, 2015

Contact: Teri L. Thiele, (515) 337-7329

Alethea M. Fry, (515) 337-7460

Approvals: /s/Steven A. Karli Date: 24Jun15

Steven A. Karli, Director

Inspection and Compliance

Center for Veterinary Biologics

/s/Byron E. Rippke Date: 26Jun15

Byron E. Rippke, Acting Director

Policy, Evaluation, and Licensing

Center for Veterinary Biologics

/s/Byron E. Rippke Date: 26Jun15

Byron E. Rippke, Director

Center for Veterinary Biologics

/s/Rebecca L.W. Hyde Date: 29Jun15

Rebecca L.W. Hyde, Section Leader

Quality Management

Center for Veterinary Biologics

United States Department of Agriculture

Animal and Plant Health Inspection Service

P. O. Box 844

Ames, IA 50010

INTERNAL USE ONLY

Mention of trademark or proprietary product does not constitute a guarantee or warranty of the product by USDA 

and does not imply its approval to the exclusion of other products that may be suitable.
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Table of Contents

1. Purpose 

2. Scope

3. Definitions

4. Policies and Objectives

5. Roles and Responsibilities

6. Processes

7. Records

8. Customer Feedback

9. Summary of Revisions
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1. Purpose

The purpose of this document is to describe the reference and reagent review and release 

procedure used by the Center for Veterinary Biologics (CVB). 

2. Scope

This document is intended to establish a process for reviewing and managing records for the 

release of CVB reagents and references (see Section 3) that are critical components in biological 

testing. This release procedure is for reagents and references qualified by the CVB, either 

manufactured by the CVB or other entities, for distribution to biologics firms or others outside of 

the CVB. Limited-Use Biologics are excluded from the scope of this document. Also, this 

process is not intended to apply to the references or reagents produced by biologics firms for 

their own master seed or release tests that do not require CVB references or reagents.

3. Definitions

3.1 Critical Component: A biologic reagent or reference that provides integral 

properties required by a test system to directly support a result or test validity.

3.2 CVB Reagent and Reference Catalog: A current list of reagents and references 

supplied by the CVB that are supported by a Reagent/Reference Folder, excluding 

Limited-Use Biologics.

3.3 Draft Production Protocol: A specific type of draft document that defines a 

production protocol for a reference/reagent that is in the developmental stage. When a 

reference/reagent is produced using a draft production protocol, the reference/reagent is 

considered to be nonstandard and a complete copy of the draft production protocol must 

be included in the reference/reagent folder. Additionally, this draft copy must be signed 

by the Section Leader (or their designee), both to provide accountability for how this 

particular reference/reagent was produced and also to document management 

acknowledgment of the production of a nonstandard reference/reagent (see

QMSOP0001, Center for Veterinary Biologics Quality Management System Documents). 

3.4 Point-of-Use Biologic: A biological agent prepared at the CVB intended for 

internal use (i.e., master seed virus). A point-of-use biologic is not required to undergo 

the review and release parameters described in this document. Manufacturing and test 

records are maintained by the CVB Laboratory Section responsible for producing this 

biological entity. Under special circumstances, CVB may supply a point-of-use biologic

to firms or other entities. The Section Leader or designee will communicate with the 

intended recipient via letter the intended use of the biological. This information is 

essential to ensure that the recipient understands this agent has not been through the 

reference and reagent review and release process. A CVBFRM3101, Point of Use
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Biologic Sign-off Form, is completed and kept in the reagent/agent file. Other relevant 

information such as a reagent data sheet may accompany the shipment. 

3.5 Production Protocol: The term used to designate a specialized SOP describing a 

specific way to carry out a production process used in the CVB Laboratory.

3.6 Reference/Reagent Folder: A single, well-organized file that includes all 

pertinent records associated with the reagent or reference. 

3.7 Standard Test Reagent (Reagent): This is a serum, antitoxin, fluorescent 

antibody conjugate, toxin, virus, bacterial culture, or antigen to be used in test systems

but not for direct comparison with serials of biological products under test. 

3.8 Standard Reference Preparation (Reference): This is a serum, virus, bacterial 

culture, cell, or antigen to be used in test systems for direct comparison with serials of 

biological products under test. 

3.9 Section: In this document, “Section” refers to the Section within the CVB 

preparing the reagent or reference.

4. Policies and Objectives

The reference and reagent review and release procedure shall meet any applicable standards 

within title 9, Code of Federal Regulations (9 CFR), part 113, and of the quality system of the 

Laboratory. This procedure is intended to provide a scientifically valid and consistent process for 

the release of reagents and references for use. In addition, this reference and reagent review and 

release procedure is designed to facilitate the continuous improvement of CVB reference 

materials and reagents supplied to the biologics industry and others. 

5. Roles and Responsibilities

5.1 Staff: Members of the CVB staff are responsible for following all procedures 

associated with reagent and reference preparation review and release. The staff is also 

responsible for following currently accepted good manufacturing and laboratory practices 

in the production and evaluation of reagents and reference preparations.

5.2 Management: CVB management is responsible for final review and approval of 

all information contained in the Reagent Folder and for providing resources and training 

required by staff to produce quality references and reagents. 
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6. Processes

6.1 In the case of a CVB-produced reference or reagent, all documentation regarding 

the production and testing of the reagent or reference is organized in a Reagent/Reference 

Folder. The cover is labeled with the product name, lot number, and responsible 

laboratory section. The Reference/Reagent Folder includes the following, in order: Table 

of Contents; CVBFRM0009, Reagent Production Sign-Off Form; CVBFRM0008, CVB 

Reference and Reagent Test Report; Reagent Data Sheet; Production or Draft Protocol;

certificate of source for ingredients of animal origin; production records; in-process 

testing; fill and label records; final product testing; and notes. An example of a

Reference/Reagent Folder template is CVBFRM3001, Documentation for Reference and 

Reagent Folder. 

6.2 In the case of third-party acquired references or reagents, the Section Leader or 

designee shall ensure copies of the production records, negotiated contract, or any other 

paperwork associated with the reagent or reference is included in the Reference/Reagent 

Folder.

6.3 Following completion of the reference or reagent, the manufacturing Section shall

review the contents of the Reference/Reagent Folder and sign CVBFRM0009. Their 

dated signature indicates that 1) the records were found to be legible and complete, and 

2) all of the required information and testing is contained in the Reference/Reagent 

Folder. 

Note: The manufacturing Section review shall not be completed by the primary

individual who produced the reagent. 

6.4 Following the manufacturing Section review, the Section Leader or their designee 

shall review the contents of the Reference/Reagent Folder and sign CVBFRM0009. 

Their dated signature indicates that 1) the records were found to be legible and complete,

and 2) all of the required information and testing is contained in the Reference/Reagent 

Folder. 

6.5 Following review by the manufacturing Section Leader or their designee, submit 

the Reference/Reagent Folder to the Lead Biologics Compliance Assistant (BCA) for 

review and release. The Lead BCA stamps the documents as received and forwards to the 

assigned Biologics Specialist. The Biologics Specialist reviews the information on 

CVBFRM0008 and compares it to the information on the Reagent Data Sheet and the 

Production Protocol. If the documentation is correct, the Biologics Specialist initials and 

dates the Reagent Data Sheet, signs and checks the APHIS disposition box on 

CVBFRM0008, signs CVBFRM0009, and returns the folder to the Lead BCA.

6.6 The Lead BCA stamps the signed documents and makes sure the appropriate 

disposition has been selected by the Biologics Specialist. 
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6.7 If the reference or reagent is signed off as Satisfactory for release by Inspection 

and Compliance (IC), the Lead BCA forwards the documents to the CVB Quality 

Management System (QMS) Program Assistant. The QMS Program Assistant scans the 

Reagent Data Sheet and CVBFRM0008 and uploads the documents to the CVB QMS 

SharePoint site, . 

6.8 The Reference/Reagent Folder is returned to the originating Section by the QMS 

Program Assistant. The product is added to the Section inventory and is available for use 

and distribution. 

6.9 If the reference or reagent does not satisfy the requirements set forth in the 

Production Protocol, the product will be considered Unsatisfactory for the intended use. 

6.10 Documentation of the disposition of unsatisfactory product, along with the 

CVBFRM0008, is to be filed in the Reference/Reagent Folder. 

7. Records 

7.1 Production and test records should be initialed (or signed) and dated by the person 

performing the work. 

7.2 Each page of all generated documentation relevant to the production, testing, 

review, and release of a reference or reagent shall be identified with the reference/reagent 

unique identification number. 

7.3 The Reference/Reagent Folder shall be filed in the CVB Laboratory Section and 

will be maintained indefinitely. 

 7.4 Fill out PIMSFRM1108, Document Publication Form, to have the reagent data 

sheet posted on the CVB Website. 

7.5 Reagent Catalog: For reagents that will be shipped to manufacturers, alert Nancy 

Clough of the Policy, Evaluation, and Licensing (PEL) Virology Section to enter the 

reagent into the Reagent Catalogue. Provide the reagent name, lot number, fill volume, 

and that the reagent is available for shipping. If the new reagent is replacing a current 

reagent, also notify her to take the old lot number off the reagent catalog. 

 7.6 If additional testing is completed on a released reagent (i.e., for reagents that have 

expiration dates that require testing to extend the expiration date, or when a reagent has 

been shared with firms for concurrent testing prior to completion of testing at the CVB) 

an updated Reagent Data Sheet needs to be approved and posted. 

7.7 All correspondence following release of the reagent, including customer 

feedback, will be saved to the CVB Lab drive under “Reagent Correspondence.”
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Documents will be saved in a corresponding file referencing agent name and specific lot 

number (i.e., Clostridium septicum toxin IRP 628).

8. Customer Feedback

8.1 The CVB Mail Box address, CVB@aphis.usda.gov, is provided on the Reagent 

Data Sheet for any feedback from the customer regarding the reagent. These emails are 

received by the IC Program Support Assistant and forwarded to individuals in the email 

group, APHIS-VS STAS CVB Reagent Requests, for appropriate action.

8.2 Any correspondence received by CVB personnel regarding a supplied reagent, 

including but not limited to emails, phone logs, mail logs, etc., should be sent directly to 

the email group, APHIS-VS STAS CVB Reagent Requests, for appropriate action. 

8.3. The laboratory section that produced the reagent is responsible for all appropriate 

follow-up to the feedback and for maintaining records documenting any correspondence 

or action taken. 

8.4 All emailed documents will be reviewed and saved by the manufacturing section 

to the CVB Lab drive under “Reagent Correspondence.” Documents will be saved in a 

corresponding file referencing agent name and specific lot number (i.e., Clostridium 

septicum toxin IRP 628).

9. Summary of Revisions

Version .09

 3.4: In definitions, changed Limited-Use Biologics to Point-of-Use Biologic and 

definition updated to reflect internal use terminology.

Version .08

 7.5: Added instructions for the Reagent Catalog.

 7.6: Added instructions for updating Reagent Data Sheets

 7.7, 8.3, and 8.4: Added information on Section Responsibility for managing 

customer concerns.

 8.1 and 8.2: Added information on routing of customer feedback received via the 

CVB Mail Box.
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 Other minor clarifications.

Version .07

 6.5: Clarified steps performed by Lead BCA and changed Quality Management 

Biologics Specialist to assigned Biologics Specialist due to pending reorganization. 

 6.6: Moved reference to returning folder to originating section from 6.6 to 6.8 -

folder will not be returned until processed. 

 6.7: Changed procedure – QMS will scan documents prior to returning to the 

originating section. Removed requirement to scan and upload CVBFRM0009 – the 

form is not required for tracking of approval. 

 6.8: The folder will be returned to the originating section after documents are scanned 

and up loaded. The originating section will not be responsible for scanning and 

emailing the documents. 

Version .06

 3: Definitions for Draft Production Protocol was updated

 Document was updated for consistency

Version .05

 The Contact information has been updated.

 This document has undergone a complete revision after extensive review by the entire 

Center.

Version .04

 3: Definitions for Draft Production Protocol and Production Protocol have been 

added. 

 3/6.5: Clarification has been added to the reference “all pertinent records of 

production”.

 6: Provision that a copy of the Production Protocol need not be provided to the QM 

Specialist if the protocol is available on the CVB Quality Management SharePoint 

site, and that any protocols or 3rd party contract provided to IC for review are CBI’d 

and not filed has been added. Provision for 2 copies of the CVBFRM0009 allowing

one copy to be retained by the ABRM Section and one to be sent to the originating 
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Section has been added. “IC-OAA” is replaced with “Lead BCA”, and the return of 

all copies to ABRM for further distribution has been added to reflect the current 

process.

 6.11: Disposition of the 3 CVBFRM0008s has been clarified.

Version .03

 3: The definition of Reagent Folder has been updated with further clarification of 

what is needed.

 5.2: The requirements for Management have been updated with further clarification 

of what is needed.

 6: The processes for reference and reagent review and release have been updated with 

further clarification of what is needed.

 The document number has been changed to CVBSOP3001 to reflect new Unit 

delineations.

 The section on “Standards and Normative References” has been removed.

 The section on “Forms and Worksheets” has been removed as these are referenced 

throughout the document.

 The section on “Monitoring Process for Effectiveness” has been removed as all CVB 

Quality Management System documents and their processes are open to audit.

 The “Appendix” has been removed and made into a self-standing form, 

CVBFRM3001.

Version .02

 PELSOP0001.02 is a revision superseding CVBPELSOP0001.01.

 CVBPELSOP0001 was changed to PELSOP0001 to reflect the new, streamlined Unit 

Abbreviations.

 Section and Reagent Folder definitions were added to the Definitions Section.

 ISO/IEC 17025 reference was removed from the Standards and Normative 

References Section as this SOP deals with reference and reagent production processes 

and not testing competency.

 CVBQASOP0001, CVB Quality Assurance Program Documents, was added to the 

Standards and Normative References Section.

 The retention date for Records (now Reagent Folders) was changed from 7 years to 

10 years to be in compliance with the APHIS Records Management Handbook.
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 Audits “as required by the CVB Quality Assurance Program” was added to the 

Monitoring Process for Effectiveness Section.

 Appendix 1, CVB Reference and Reagent Test Report, was removed as that 

information is now captured on CVBQAFRM0008, current version.

 CVBFRM0001.01 and CVBPELFRM0002.01 were removed from the end of this 

SOP, as they were not an official part of the document. Both of these forms have been 

retired.

 General clarification of duties and processes and adjustments to formatting have been 

made throughout this SOP. Refer to the “Track Changes” copy for specifics.