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Animals > Veterinary Biologics > Guidelines / Forms

Veterinary Biologics Guideline 3.7E

Guidelines for Preparation of Production Outlines, Special Outlines and Summary of Changes for Veterinary Biologics

INTRODUCTION

The approved PRODUCTION OUTLINE serves as an agreement between the manufacturer and the licensing agency on acceptable production and testing methods for each product. In addition to preparing a PRODUCTION OUTLINE for each licensed product, most firms also prepare a set of SPECIAL OUTLINES which describe standard procedures which are used for more than one product. Changes in production methods are documented by submitting amended PRODUCTION OUTLINE pages and a SUMMARY OF CHANGES. Each of these documents must be signed by the manufacturer's authorized representative and submitted for approval.

We recommend that Canadian biologics manufacturers adopt a standard format when preparing a PRODUCTION OUTLINE, SPECIAL OUTLINE, or SUMMARY OF CHANGES. Examples of recommended formats for the PRODUCTION OUTLINE and SPECIAL OUTLINE are shown on the attached pages. This standard format was adapted from the USDA-APHIS format, which is widely used in the veterinary biologics industry.

The standard format and headings are applicable to all veterinary biologics; however, modifications may be required for some products such as veterinary diagnostic test kits. Guideline 3.19, Guidelines for Licensing Veterinary Diagnostic Test Kits in Canada, provides further information and recommendations for preparing production outlines for these products.

The cover page for the PRODUCTION OUTLINE should contain the manufacturer's name and address, assigned product name, establishment license number, and date. Subsequent pages should contain a header with the same information, except the manufacturer's address.

The SPECIAL OUTLINES can be cited in the PRODUCTION OUTLINE to reduce duplication of text and simplify the format for the PRODUCTION OUTLINE. SPECIAL OUTLINES should have a descriptive title and be numbered consecutively. They are formatted similar to the text pages of the PRODUCTION OUTLINE.

All changes in production and testing procedures must be documented and submitted for approval. Minor changes can be documented by submitting the amended PRODUCTION OUTLINE pages with an attached SUMMARY OF CHANGES (see example). Major changes may necessitate a complete revision of the production outline, or designation as a new product. Proposals for major revisions should be submitted in advance so that our office can review and comment on the changes.

Canadian manufacturers should submit three copies of the production outline. One stamped approved copy will be returned to the manufacturer, one stamped copy will be forwarded to Biologics Evaluation Laboratory (BEL), and one stamped copy retained in Veterinary Biologics Section (VBS) files. American manufacturers should submit two copies of the production outline if the serials will not be tested in Canada, and three copies if serials will be tested in Canada.

Manufacturers should review all production outlines annually, and submit the revisions for approval. Test references on serial release test result forms should cite the current production outline and special outlines.

RECOMMENDED FORMAT FOR PRODUCTION OUTLINE - COVER PAGE

Company Name
Street Address
City, Province
Postal Code

Production Outline

Product Name (Assigned Generic Name)

Product Code (USDA-USDA-APHIS Product Code or VBS File Number)

Veterinary Biologics Establishment No. _____

Date (Month, day, Year)

RECOMMENDED FORMAT FOR PRODUCTION OUTLINE - SUBSEQUENT PAGES

The format described below was adapted from the format developed by the USDA-APHIS Veterinary Biologics Staff for preparing production outlines, and published in the United States Code of Federal Regulations (9-CFR 114.9). Canadian manufacturers are encouraged to adopt this format to facilitate licensure in Canada, as well as the United States and other countries.

For each page, leave at least a one inch margin on all sides

-Page-

Manufacturer:
Establishment Licence:

Date: Month / Day / Year
Supersedes: Month / Day / Year

Product Assigned Name

Product Code (USDA--APHIS Product Code or VBS File Number)

I.	COMPOSITION OF THE PRODUCT
A.	Micro-organisms used.
	List the micro-organisms used and indicate the isolation and passage history.
B.	Source and date of accession.
	Indicate for each micro-organism.
C.	Strains.
D.	Proportions of each strain or subunit in product.

II.	CULTURES
A.	Identification.
	Indicate the methods used to identify micro-organisms in master seed and production seed.
B.	Virulence and purity of cultures.
	Indicate the methods used to determine virulence and purity of cultures.
	Also indicate the range of subcultures to be used in production.
C.	Composition of media used for seed and production cultures.
	Indicate composition and source of media and other materials of animal origin (cell culture, serum, eggs, birds or animals). Also indicate methods used to determine that the above materials are free from contaminants.
D.	Character, size, and shape of containers used for growing cultures.
E.	Storage conditions for seed cultures.
F.	Methods for preparing suspensions for inoculation.
G.	Technique for inoculating seed and production media.
	Indicate the titer or concentration of inoculum, and the volume of media for each container.
H.	Incubation times, temperatures, conditions.
I.	Character and amount of growth.
	Indicate expected characteristics of cultures (physical appearance), and any observations of possible contaminants.
J.	Method for attenuation or inactivation, if applicable.

For each page, leave at least a one inch margin on all sides

-Page-

Manufacturer:
Establishment Licence:

Date: Month / Day / Year
Supersedes: Month / Day / Year

Product Assigned Name

Product Code (USDA--APHIS Product Code or VBS File Number)

III.	HARVEST
A.	Handling and preparation of cultures prior to harvest.
B.	Minimum and maximum elapsed incubation time for cultures.
C.	Harvest techniques.
D.	Specifications for acceptable harvest.
E.	Handling of discarded material.
F.	Additional pertinent information.

IV.	PREPARATION OF THE PRODUCT
A.	Method of Inactivation, attenuation, or detoxification.
B.	Composition of preservative, adjuvant, or stabilizer.
C.	Methods used to concentrate and purify product.
D.	Standardization of antigen(s) concentration in product.
E.	Assembly of serials:
	Describe method used to make a serial from lots of production material. Volume of average serial. Volume of maximum serial. Additional pertinent information.
F.	Volume of fill (min/max) for each vial size. Vial type.
G.	Method and technique of filling and sealing final containers.
H.	Lyophilization method, if applicable. Maximum moisture.
I.	Amount of antigenic material per dose.

For each page, leave at least a one inch margin on all sides

-Page-

Manufacturer:
Establishment Licence:

Date: Month / Day / Year
Supersedes: Month / Day / Year

Product Assigned Name

Product Code (USDA--APHIS Product Code or VBS File Number)

V.	TESTING
A.	Purity. Test for freedom from residual live bacteria and contaminants. Test for viable bacteria, fungi, and mycoplasma as described in the USDA--APHIS 9-CFR 113.26, 113.27, 113.28 or equivalent method.
B.	Safety. Method to be submitted for approval.
C.	Potency. Method to be submitted for approval.
D.	Moisture determination for lyophilized products.
E.	Any other tests.
Example: residual formaldehyde determination.

VI.	POST PREPARATORY STEPS
A.	Form and size of final containers.
B	Sample Collection and Submission.
C.	Expiration date.
D.	Label recommendations.
	Indicate intended use, dose, route of administration, and precautions.
E.	Statement of confidentiality of information in production outline.

Signature

Name, Title

RECOMMENDED FORMAT FOR PRODUCTION OUTLINE - SUMMARY OF CHANGES

The following is an example of the format for documenting amendments to an approved PRODUCTION OUTLINE. When revisions are necessary, the amended production outline pages and a SUMMARY OF CHANGES are submitted for approval. After approval, the amended pages are inserted into the PRODUCTION OUTLINE, to replace the original pages. The SUMMARY OF CHANGES is attached to the approved production outline, and serves as documentation for all changes which have been approved since the original PRODUCTION OUTLINE was prepared.

For each page, leave at least a one inch margin on all sides

Manufacturer:
Establishment Licence:

Date: Month / Day / Year
Supersedes: Month / Day / Year

Product Assigned Name

Product Code (USDA--APHIS Product Code or VBS File Number)

Summary of Changes

Section Description of Changes

III.	A.	Harvest method changed from .......... to ............
IV.	A.	Inactivating agent changed from ...... to ...........
IV.	E.1.	Sentence rewritten to clarify method for .......
V.	C.	Potency test changed from ............... to ............
V.	F.	Deleted .......
VI.	B.	Added ..........

Signature

Name, Title

RECOMMENDED FORMAT FOR SPECIAL OUTLINE - COVER PAGE

For each page, leave at least a one inch margin on all sides

-Page-

Manufacturer:
Establishment Licence:

Date: Month / Day / Year
Supersedes: Month / Day / Year

Special Outline No. ____

Title (e.g. Method for Preparation of Leptospira hardjo Culture Media)

(description of materials and methods)

Signature

Name, Title

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