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Veterinary Biologics Guideline 3.7E
Guideline for Preparation of Outlines of Production, Special Outlines and Summary of Changes for Veterinary Biologics
Table of Contents
- I. Introduction
- II. General Requirements
- III. Outlines of Production
- IV. Special Outlines
- V. Revisions to Outlines of Production and Special Outlines
- VI. Special Considerations for Manufacturers in the United States
- VII. References
- VIII. Templates of Required Formats
VIII.A. Required Format for Outline of Production - cover page - all products
VIII.B. Required Format for Outline of Production - Subsequent Pages
VIII.C. Required Format for Summary of Changes of Outline of Production
VIII.D. Required Format for Special Outline
- VIII.E. Required Format for Summary of Changes of Special Outline
I. Introduction
The purpose of this document is to inform veterinary biologics manufacturers of the requirements for Outlines of Production (OPs) and Special Outlines (SOs). This guideline is directed primarily at Canadian manufacturers and foreign manufacturers in countries other than the United States (US). The OP and SO requirements of US manufacturers may differ in some aspects, and these differences are described in Section VI.
The OP written by the manufacturer for a veterinary biologic is a legally binding document describing the methods of veterinary biologic production and analysis, which is followed by the manufacturer and has been accepted by the Canadian Centre for Veterinary Biologics (CCVB) of the Canadian Food Inspection Agency (CFIA). In addition to the OP, most firms also prepare a set of SOs to describe culture media, reagents and standardized procedures used for more than one product, or the tests used to analyse one product specifically. Changes (revisions) made to an OP or SO are described in a Summary of Changes document that must accompany an OP or SO revision submission. All revisions to OPs and SOs related to products serial released in Canada must be approved by CFIA-CCVB before their implementation at the manufacturer's level.
Manufacturers of veterinary biologics are required to adopt a standard format when preparing the documents described above. Templates with the recommended format for OPs, SOs and Summaries of Changes are provided in Section VIII.
A. Legal Authority
The Health of Animals Regulations requires that the production, packaging, labelling and testing of all veterinary biologics conform with the specifications written in the product outline [OP] of the product, which has been approved by CFIA-CCVB.
II. General Requirements
A. Required Format
For all OPs, SOs and Summaries of Changes a 2.5 cm margin is required at the top, left and right sides, and a margin of at least 5 cm at the bottom of all pages for the CCVB approval stamp.
B. Drafts of Outlines of Production and Special Outlines
The versions of OPs and SOs that are submitted to CCVB for the Canadian licensing of any new veterinary biologic are considered drafts until these documents are finally approved (dated CCVB stamp on each page). Modifications and corrections done to these draft OPs and SOs during the evaluation of the new product file are not treated as revisions and do not require the submission of a Summary of Changes. However, each new complete version of the OP or SO must show a new date in order to distinguish it from the previous version.
C. Number of Copies to be Submitted for Review
For new product submissions, manufacturers are required to submit three original copies of the final drafts of the OP and the SOs signed on the last page by the authorized person at the manufacturer's level. After approval (CCVB stamp), one stamped approved copy will be returned to the manufacturer, one stamped copy will be forwarded to the Biologics Evaluation Laboratory (BEL), and one stamped copy is retained in the files at CCVB.
D. Outlines of Production and Special Outlines of Canadian Manufacturers Exporting to the United States
Veterinary biologics manufactured in Canada can be licensed in the US through a “Permittee” located in the US. In this situation, the Canadian manufacturer is then required by CCVB to have only one version of the content of the OPs and SOs for these products. The assigned name of the product must be the same on the two OPs (Canadian and US versions) and the numbers given to the Canadian versions of the SOs. must remain the same for the SOs of the “Permittee”. The only differences are the identification of the Canadian manufacturer compared to the “Permittee” in the US, and the respective requirements for serial release.
III. Outlines of Production
A. Required Format
The content and standard format of OPs are distinct for the three main categories of veterinary biologics: 1- vaccines, bacterins, antigens and toxoids; 2- veterinary diagnostic kits; and 3- antibody products. Section VIII contains templates outlining the section headings and information requirements for each of these three product types. All of the section and subsection titles shown on the template must be written in the OP prepared by the manufacturer. If a certain section or subsection does not apply to the product involved, it is then necessary to write “N/A” for “Not applicable”.
1. Cover Page - The cover page for the OP must contain the manufacturer's name and address, the assigned product name, the CCVB product file number, the establishment licence number (Canadian manufacturer) or its equivalent (foreign manufacturer), and the date. Refer to the template provided in Section VIII.A. The cover page does not count when numbering pages in the OP (i.e. page 1 is assigned to the first subsequent page).
2. Subsequent Pages - All subsequent pages of the OP must contain a header with the same information as the cover page, with the exception of the manufacturer's address (optional). The six main sections of the OP are indicated by capitalized roman numerals (I., II., III., IV., V., and VI.), and the subsections by capitalized letters (A., B., C., D., etc.). Subdivisions first use arabic numbers (1., 2., 3., 4., etc.), then lower case letters (a., b., c., d., etc.) and lastly roman numbers in lower case letters (i., ii., iii., iv., etc.) [example: IV.B.3.d.vi.]. If multiple listings are needed within one such subdivision [example: IV.B.3.d.vi.], it is then recommended to use double lower case letters (aa., bb., cc., etc.). It is also recommended to identify the section and subsection at the upper left corner of a new page when the content of that section and subsection is continued from the previous page.
For further information regarding OP content and layout, refer to the templates provided in Section VIII.B.1. (Vaccines, Bacterins, Antigens and Toxoids), VIII.B.2. (Veterinary Diagnostic Kits), or VIII.B.3. (Antibody Products).
IV. Special Outlines
A. Special Outlines and Standard Operating Procedures
SOs are cited in an OP or in other SOs to reduce the duplication of text, and to simplify the format of these parent documents. SOs must have a descriptive title and must be numbered consecutively. They are formatted similar to the text pages of the OP (see below).
Foreign manufacturers, other than those in the US, generally prepare Standard Operating Procedures (SOPs) to describe the composition of media and numerous methods or techniques used to manufacture a veterinary biologic product. These SOPs are usually found acceptable as substitutes for SOs when they are signed and dated, even if the format of these SOPs differs from the format of SOs. In this situation, certified photocopies of all the SOPs associated with a product file for licensing (i.e. all SOPs referenced in the OP and in the main SOPs) must be submitted by the foreign manufacturer to CCVB for review. For the purpose of this guideline, manufacturers approved to use SOPs instead of SOs should follow the procedures indicated for SOs where applicable.
Note 1: CCVB can request the preparation of SOs according to the format described in this guideline if the SOPs submitted by the manufacturer are deemed unsatisfactory.
B. Required Format
Templates outlining the format and content of the cover page and subsequent pages of an SO are provided in Section VIII.D.1 and VIII.D.2, respectively.
C. Documentation on Materials of Animal Origin
For each product intended for manufacture or importation into Canada, a list must be supplied of all materials of animal origin (MAO) that have been either used directly in its production or have been in contact with any of its constituents during development and/or production. For each listed material, the manufacturer must indicate the country of origin, animal species, tissue of origin, supplier's name and address, and provide a signed and dated supplier's certificate (or European Directorate for the Quality of Medicines (EDQM) Certificate of Suitability) indicating actions taken to minimize the risk for contamination of their product by animal TSE agents (i.e. country of origin, animal species, health status of source animals). Vaccines and antibody products must not contain any material defined as Specified Risk Material. More information on the required MAO documentation can be found on the CFIA-CCVB website.
Documentation on MAO should be compiled into an SO. As with other SOs, three original copies of the MAO SO are required. However, only one copy is required of the certificates of origin or of analysis and of the supplier's certificates. These documents are placed in the Appendices to the MAO SO, and are not stamped but kept on file at CCVB as mandatory information.
V. Revisions to Outlines of Production and Special Outlines
All revisions to OPs and SOs related to products serial released in Canada must be approved by CCVB prior to their implementation at the manufacturer's level, regardless of whether they involve major or minor revisions.
A. Frequency
It is recommended that manufacturers perform an annual document review to identify any required changes to their OPs or SOs. If the changes sought by the manufacturer significantly modify the production method or testing for serial release (i.e. for an OP includes a Major Revision - see V.E.1.), the manufacturer is required to submit this revision for approval as soon as possible. If the changes are minor, the manufacturer can accumulate these and submit them to CCVB for approval as part of an annual revision.
Note 2: If the current stamped-approved version of an OP or SO includes pen-and-ink corrections made by CCVB at the time of its approval, the manufacturer is required to incorporate these pen-and-ink corrections during the next revision.
Note 3: When a proposed partial revision results in 50% or more of the pages of an OP (or SO) having been modified since the previously accepted complete revision, the manufacturer must instead submit the desired change(s) as part of a new complete revision to the OP (or SO).
B. Number of Copies
Manufacturers are required to submit three original copies of the revised pages of the OP or of the SO signed by the authorized person at the manufacturer's level, together with three signed original copies of the Summary of Changes.
C. Summary of Changes
The Summary of Changes is a separate document prepared by the manufacturer summarizing all of the changes (additions, removals, corrections) made to the OP or SO as part of the current revision. The location of the changes must be accurately described, referencing sections and subsections, as page numbers may change from revision to revision. The Summary of Changes pages must have a header that includes the identification of the manufacturer and the name of the product (or title of SO). Only the date of the revision submitted for approval is required in the heading. If the Summary of Changes includes more than one page, pages are numbered starting with page 1. The Summary of Changes must be signed by the authorized person at the manufacturer's level. Templates for Summary of Changes documents that must accompany an OP or SO revision are provided in Section VIII.
D. Submission for Approval
The submission of revisions to OPs and SOs must include 1) a covering letter, 2) the revised page(s), 3) the signed Summary of Changes, and 4) form CFIA/ACIA 4720 with the appropriate fee payment. For partial revisions of previously approved OPs and SOs, each revised page must be signed by the authorized person at the manufacturer's level. For complete revisions, only the last page of the OP needs to be signed.
The subsequent pages (i.e. all pages except the cover page) of an OP and SO contain a field in the heading to write the date of the superseded version. When only individual pages are being revised, the date of the previous CCVB-approved version of that page is written at “Supersedes”. For a complete revision of an OP or SO, the date of the previous complete version approved by CCVB is written at “Supersedes”. Additionally in the case of a compete revision, the cover page of the OP or SO must be resubmitted with the words “Complete Revision” placed below the revision date on the cover page.
When the changes to a single revised page exceed the space available, the surplus text is transferred to a new page bearing the same number followed by the letter “a”. If more than one page is required for the change, additional pages retain the same number with consecutive letters “a”, “b”, “c”, etc.
Note 4: If more than one OP is applicable to the file of a product licensed in Canada (OPs of fractions used in the assembly of a final product when there are no separate product files for these fractions), one single fee is charged for the submission of revisions to multiple OPs related to a single product file, as long as the revisions to these OPs are submitted together.
E. Revisions to Outlines of Production
The cover letter accompanying the revision submission package must indicate whether the desired changes to an OP involves Major or Minor Revisions. Manufacturers concurrently submitting revisions to multiple OPs must prepare a separate cover letter specific to each product file.
1. Major Revisions - Major Revisions are those changes to an OP that can impact upon the purity, safety, potency and/or efficacy of the product. Again, Major Revisions must be submitted to CCVB for approval as soon as possible (and prior to their implementation), and require the co-submission of supporting data or research reports. Revisions to the items listed below (grouped according to product type; section of OP provided in brackets) are considered Major Revisions.
Note 5: Under certain circumstances, a change in the production of a veterinary biologic will require the submission of a new product file rather than the filing of an OP Major Revision for the existing licensed product. For example: 1- Replacement and/or substitution of Master Seed micro-organisms or Master Cell Stock, multiple changes in media and adjuvant used in the production of vaccine, bacterin or toxoid; 2- Replacement and/or substitution of monoclonal antibody(-ies)/antigen(s) used in the production of diagnostic test kits; 3- Change in the species of animal used to produce antibody products. All of the above changes would require comprehensive efficacy and field safety studies (not just bio-equivalence data for vaccines, bacterins, toxoids and antibody products) or field performance data (diagnostic kits), and hence would warrant designation as new veterinary biologic products to replace existing products.
a. Vaccines, bacterins, antigens and toxoids
- Master seeds (section I.A.)
- Master cell lots and materials of animal origin (MAO) (section II.C.)
- Method of inactivation, attenuation or detoxification (section IV.A.)
- Composition of preservative, adjuvant or stabilizing agent (section IV.B.)
- Quantity of antigenic material per dose in final container (section IV.I.)
- Tests (section V.)
- Expiry date (section VI.C.)
- Use, dose, route of administration and precautions (section VI.D.)
Note 6: Test procedures used to certify that live viral vaccines for ruminants do not contain bluetongue virus (BTV) and that those for swine do not contain pseudorabies virus (PRV) are not specified in OPs, unless the manufacturer obtained an exemption after the certification of the master seeds and master cell lots. Any change related to the procedure of these tests is considered a Major Revision and must be submitted to CCVB for approval before implementation.
b. Veterinary diagnostic kits
- Nature of polyclonal antibodies (section I.A.)
- Nature of monoclonal antibodies (section I.B.)
- Master seeds of micro-organisms used in the kit (section II.A.)
- Master cell lots and MAO (section II.B.)
- Extraction and characterization of the antigen (section II.C.)
- Standardization of antigen and acceptability criteria (sections II.D. and II.E.)
- Nature of positive and negative controls in the kit, including new lots (section III.A.)
- Nature of other reagents in the kit (sections III.B. and III.C.)
- Method of filling, spreading or binding of the antigen or antibody (section IV.2.)
- Tests to verify the performance of the kit and its serial release (section V.C.)
- Nature of the reference panel members (section V.C.)
- Modification to the reference panel members (section V.C.1.)
- Expiry date (section VI.C.)
- Use, test limitations and interpretation (section VI.D.)
c. Antibody products
- Serological tests or other tests for the selection of animals (section I.B.)
- Antigens and micro-organisms used in the immunization (sections II.A., II.B., II.C. and II.D.)
- Culture media and cell lines used for the propagation (section II.F.)
- Preparation of the antigen, toxin or toxoid (section II.G.)
- Method of inactivation or detoxification (section II.G.)
- Characteristics and dose of the inoculum for the animals (sections III.A.1. and III.A.2.)
- Characteristics of an acceptable harvest and required tests (section III.A.6.)
- Statement on MAO (section III.A.6.a.)
- Composition of preservative (section IV.B.)
- Quantity of immunoglobulins per dose(s) in the final container (section IV.C.)
- Method of lyophilization, drying, pulverizing, etc. (section IV.H.)
- Testing (section V.)
- Expiry date (section VI.C.)
- Use, dose, route of administration and precautions (section VI.D.)
Note 7: Any changes made to the sections identified above that involve simply correcting spelling, typographical or grammatical errors, rewording or reformatting the text, or modifying the nomenclature (technical or usual term); or that pertain to ingredients other than those listed above; or that represent minor adjustments to manufacturing procedures or equipment are considered to be Minor Revisions to the OP (see V.E.2. below).
2. Minor Revisions - Minor Revisions to an OP are those changes that are not likely to impact on the purity, safety, potency and efficacy of the product. Minor Revisions must be submitted to CCVB at least once annually for each OP or each product file.
The revisions done to sections of the OP other than those identified in V.E.1. above are considered Minor Revisions. For example, a change in the source of ingredients (with the exception of bulk antigen and MAO) is considered a Minor Revision, as long as the substitution is done with an ingredient of similar quality.
In order to allow the filing of OP Minor Revisions without in-depth review, it is necessary that the manufacturer, or its designated official representative, certifies that the submitted revisions do not include any Major Revision, as described in the present guideline, by signing the covering letter.
F. Revisions to Special Outlines
Revisions to SOs should be categorized based on whether or not the SO in question describes the methods of preparation and/or the testing of a bulk or final veterinary biologic. This distinction must be identified in the cover letter accompanying the SO revision submission. Similar to Major Revisions, revisions to SOs that affect production or testing must be submitted to CCVB for review as soon as possible, and must be accompanied by supporting documentation. Revisions to all other SOs may be submitted annually.
Note 8: There is no fee for the review or filing of SO changes.
VI. Special Considerations for Manufacturers in the United States
US manufacturers need to submit only one copy (photocopy) of an OP or SO for CCVB approval if the product is not tested in Canada (i.e. product licensed and tested in the US; OP or SO stamped by the Center for Veterinary Biologics (CVB) of the US Department of Agriculture (USDA) Animal and Plant Health Inspection Services (APHIS)).
Note 9: For an SO written to provide information on MAO, if this SO is not approved by the USDA-APHIS-CVB but instead by CFIA-CCVB, three original copies of the MAO SO are required. (In all cases only one copy is required of the certificates of origin or analysis and of the supplier's certificates contained in the appendices of the MAO SO).
For submission and evaluation of revisions to OPs and SOs related to veterinary biologics manufactured in the US and regulated by the USDA-APHIS-CVB, CCVB requires the following documents:
- Form CFIA/ACIA 5212 for the submission of revisions (no covering letter required)
- Form CFIA/ACIA 4720 [applicable fee per article 10.(2)] (no fees for SOs)
- One photocopy of revised pages or completely revised OP or SO
- One photocopy of all corresponding Summary of Changes
- One photocopy of all corresponding APHIS Form 2015 showing USDA-APHIS-CVB disposition
- One copy of applicable supporting data
Note 10: The use of the form CFIA/ACIA 5212 for OPs and SOs only applies in the following circumstances:
a. OPs and SOs have already been filed at USDA-APHIS-CVB
b. OPs and SOs correspond to products already licensed in Canada (listed on an annual import permit)
The use of the form CFIA/ACIA 5212 for OPs and SOs does not apply in the following circumstances:
a. Submission of documents for the file of a new product submission under evaluation and not yet licensed in Canada.
b. Products manufactured in US only for export to Canada and serials are released by CFIA-CCVB.
c. MAO SO written for and approved by CFIA-CCVB
Revisions to OPs or SOs that include only minor changes are filed at CCVB without in-depth review. Major changes are evaluated by CCVB, and must be submitted with supporting data (where applicable) as soon as possible after their approval by USDA-APHIS-CVB. After successful filing of the update, the submitted form CFIA/ACIA 5212 is signed by a designated person at CCVB and returned to the submitter. One photocopy of this form is kept in the product file.
VII. References
- Code of Federal Regulations - Title 9 - Animals and Animal Products - Part 114.9. US Government Printing Office, Washington.
VIII. Templates of Required Formats
Note 11: The explanations pertinent to the expected content of the sections (i.e. the text between [....]) are provided as information only and must not appear in the OP submitted to CCVB.
VIII.A. Required Format for Outline of Production - Cover Page - all products
Company Name (manufacturing site)
Street Address
City, Province
Postal Code
Country
Outline of Production
Product Name (Assigned Generic Name)
CCVB Product File Number:
Canadian Veterinary Biologics Establishment Licence No.
(or the Manufacturing Authorization or equivalent of the foreign country of origin)
Date: yyyy-mm-dd (year-month-day)
VIII.B. Required Format for Outline of Production - Subsequent Pages
1. Vaccines, bacterins, antigens, toxoids
-Page-
Can. Vet. Biol. Estab. Lic. No.
[or Foreign Estab. Lic. / city, country]
Supersedes: yyyy-mm-dd
Product Assigned Name
CCVB Product File Number
I. Composition of the Product
A. Micro-organisms used.
D. Proportions of each strain or subunit in product.
II. Cultures
A. Identification.
- Statement pertinent to materials of animal origin [in order to minimize contamination with agents of transmissible spongiform encephalopathies]
E. Storage conditions for seed cultures.
F. Methods for preparing suspensions for inoculation.
G. Technique for inoculating seed and production media.
I. Character and amount of growth.
III. Harvest
A. Handling and preparation of cultures prior to harvest.
B. Incubation
D. Specifications for acceptable harvest.
E. Handling of discarded material.
F. Additional pertinent information.
IV. Preparation of the Product
A. Inactivation, attenuation, or detoxification
E. Assembly of serials:
- Method
[Describe method used to make a serial from lots of production material]. - Volume of average serial.
- Volume of maximum serial.
- Additional pertinent information.
V. Testing
A. Purity.
E. Any other tests.
VI. Post Preparatory Steps
A. Form and size of final containers.
B. Sample collection and submission.
C. Expiration date.
D. Label recommendations.
Signature
Name, Title
2. Veterinary diagnostic test kits
-Page-
Can. Vet. Biol. Estab. Lic. No.
[or Foreign Estab. Lic. / city, country]
Supersedes: yyyy-mm-dd
Product Assigned Name
CCVB Product File Number
Introduction
[Brief description of the test: principle of the test (ELISA, immunoblot, etc.); detection of antibody or antigen; samples to be tested (whole blood, serum, faeces, lymph nodes, brain obex, etc.); list of enclosed reagents, reference controls, and equipment; identify components from elsewhere (for further manufacture); general description of the test and its limits, including additional tests].
I. Antibody Components
A. Production of polyclonal antibody.
[2. Components prepared by manufacturer: describe criteria (animals, age, weight, conditions, etc.)]
b. Immunization of animals
ii. Describe route (injection, per os, aerosol, immersion) and schedule of immunization
iii. Describe collection of samples to verify seroconversion, evaluation tests and acceptability criteria
iv. Indicate number and interval of collections, volume obtained and other pertinent information].
B. Production of monoclonal antibody.
b. If prepared by manufacturer, identify the antigen(s) used, immunization method, and animal species used.
c. Identify the tissue of origin, and the procedures to harvest, isolate and identify the immune cells.
d. Describe the source, the identity and the product secreted (light or heavy chain) by the master cell stock of the myeloma.
e. Summarize the cloning and recloning procedures, with its characterization and propagation as needed.
f. Describe as needed the procedure to establish and maintain lots of master cell stocks
g. Describe all other tests done on the myeloma cell line as required].
b. Indicate acceptability criteria of monoclonal antibody, including purity tests.
c. Describe all tests or methods used to ensure uniformity between lots of monoclonal antibody. Include reaction conditions, equipment used and reactivity of component.
d. Describe characterization procedures and include expected reactivity of all reference monoclonal antibodies].
II. Preparation of Antigen
A. Identity
III. Preparation of Standard Reagents
A. Positive and negative controls in the kit.
IV. Preparation of the Product
[Describe methods used to standardize the bound antigens or antibodies in the kit, the reference antigens or antibodies, the negative and positive control sera, and also the standardized reagents from their preparation/purchase until the assembly of the kit in their final container. Include the data thereafter].
- Composition and quantity of preservative(s).
- Method of filling, spreading, or binding of the antigen(s) or antibodies to the solid phase.
- Minimum and maximum volumes of filling
[container of each reagent in the kit]. - Discarding method of unsatisfactory material.
V. Testing
[Refer to all applicable standardized requirements].
A. Purity
- Reference panel
[Indicate the number of panel members (about 20), their identification and their respective level of reactivity [negative, strong positive, weak positive, dubious]. - Serial release
[Briefly describe the test for the verification of the performance of the kit before the release of the serial]. - Other tests
[Describe as appropriate].
VI. Post Preparatory Steps
A. Form and size of final containers
C. Expiration date.
D. Label recommendations.
Signature
Name, Title
3. Antibody products
-Page-
Can. Vet. Biol. Estab. Lic. No.
[or Foreign Estab. Lic. / city, country]
Supersedes: yyyy-mm-dd
Product Assigned Name
CCVB Product File Number
I. Donor Animals [Mammals, birds, fish]
A. Species, conditions, age, and health status.
B. Pre-immunization care
II. Antigen used for the Immunization
A. Antigens - Composition and characteristics of antigen(s)
- List of micro-organisms used and criteria of acceptance.
- List of suppliers and date of accession for each micro-organism.
- Strains.
- Proportions of each micro-organism and strain.
III. Immunization of Animals
A. Description
- Description and dose of antigen(s); description of adjuvant [source, assigned name, serial number, expiry]
- Route [injection, per os, aerosol, immersion] and schedule of immunization.
- Time required [for the immunization or hyperimmunization]
- Collection of samples and tests used [to verify seroconversion]
- Treatments [Describe any treatment of the animals between collection of samples]
- Verification tests [Indicate type of test(s) used to verify antibody level]
- Statement pertaining to material of animal origin [In order to minimize risk of contamination with agents of transmissible spongiform encephalopathies].
IV. Preparation of the Product
A. Description
V. Testing
[Indicate the steps during the preparation of the product when samples are taken. Make reference to standardized requirements. Make a detailed list of required additional tests and specify the minimum requirements for acceptable tests].
A. Purity.
C. Potency.
D. Determination of moisture level for lyophilized or dehydrated products.
E. Any other tests.
VI. Post Preparatory Steps
A. Form and size of final containers.
B. Methods and techniques of filling.
Signature
Name, Title
VIII.C. Required Format for Summary of Changes of Outline of Production
The following is an example of the format for documenting amendments to an OP already approved by CFIA-CCVB. When revisions are necessary, the amended production outline pages and a Summary of Changes are submitted to CCVB for approval. After approval, the amended pages are inserted into the OP, to replace the original pages. The Summary of Changes is attached to the approved OP, and serves as documentation for all changes which have been approved since the original OP was prepared.
-Page-
Can. Vet. Biol. Estab. Lic. No.
[or Foreign Estab. Lic. / city, country]
Product Assigned Name
Product identification [CCVB Product File Number or USDA-APHIS Product Code]
Summary of Changes
Section Description of Changes
II.B.3.c. - “Spelling of ... corrected as per pen-and-ink change by CFIA-CCVB”
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
VIII.D. Required Format for Special Outline
1. Cover Page
Company Name (manufacturing site)
Street Address
City, Province
Postal Code
Country
Special Outline Number:
Title of Special Outline
Canadian Veterinary Biologics Establishment Licence No.
(or the Manufacturing Authorization or equivalent of the foreign country of origin)
Date: yyyy-mm-dd (year-month-day)
2. Subsequent Pages
-Page-
Can. Vet. Biol. Estab. Lic. No.
[or Foreign Estab. Lic. / city, country]
Supersedes: yyyy-mm-dd
Special Outline Number:
Title [Example: Method of preparation of the culture medium for
Leptospira hardjo].
Introduction: [Specify which products (list of CCVB product file numbers or USDA product codes with the assigned names of the products) make reference to this special outline].
I.
II.
etc.
[description of materials and methods]
Statement of confidentiality of information in special outline.
Signature
Name, Title
VIII.E. Required Format for Summary of Changes of Special Outline
The following is an example of the format for documenting amendments to a SO already approved by CFIA-CCVB. When revisions are necessary, the amended pages and a Summary of Changes are submitted to CCVB for approval. After approval, the amended pages are inserted into the SO, to replace the original pages. The Summary of Changes is attached to the approved SO, and serves as documentation for all changes which have been approved since the original SO was prepared.
-Page-
Can. Vet. Biol. Estab. Lic. No.
[or Foreign Estab. Lic. / city, country]
Special Outline Number:
Title [Example: Method of preparation of the culture medium for
Leptospira hardjo].
Summary of Changes
Section Description of Changes
Introduction - “Spelling of ... corrected as per pen-and-ink change by CFIA-CCVB”
Introduction - “New product ... added to the list”
II. - “Concentration of ... changed from ... to ...”
III. - “Incubation time changed from ... to ...”
IV.B. - “Deleted ... “
IV.C. - “Added ...”
Signature
Name, Title
