Veterinary Biologics Guideline 3.13E
Guideline for Autogenous Veterinary Biologics

Table of Contents

• I. Introduction
• II. Legal authority
• III. General guidance
  1. Basic Criteria
  2. Roles and Responsibilities of the Attending Veterinarian
  3. Roles and Responsibilities of the Manufacturer
• IV. Production of Autogenous Veterinary Biologics
  1. Facility and Personnel Requirements
  2. Data and Documentation Requirements
  3. Labelling of Autogenous Veterinary Biologics
  4. Requirements for Production and Use of Multivalent Autogenous Biologics
  5. Requirements for Production and Use of Autogenous Biologic in Adjacent and Non-Adjacent Premises
  6. Requirements for Production and Use of Autogenous Biologics in the Second Year
  7. Requirements for Production and Use of Autogenous Biologics Beyond the Second Year
  8. Specific Requirements and Restrictions for Production and Use of Autogenous Killed Viral Vaccines
  9. Serial Release Procedure for Autogenous Biologics, Including Autogenous Killed Viral Vaccines
  10. Requirements for Production of Autogenous Biologics for Export to Foreign Countries
  11. Requirements for Importation of Autogenous Biologics from the United States
  12. Requirements for Manufacturers in Countries other than the U.S.
  13. Record Keeping
  14. Restrictions on Advertisement of Autogenous Biologics
  15. Miscellaneous
• V. Further Information
• VI. References
• VII. Appendices
  • Appendix I - Fee schedule for autogenous biologics
  • Appendix II - Sample copy of Manufacturer's Serial Release Test Report (MSRTR)
  • Appendix III - Information Required for Autogenous Veterinary Biologics

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I. Introduction

This guideline provides information on requirements for manufacturing, importation and distribution (including exportation) of autogenous veterinary biologics for use in animals.

The information contained in this guideline is also applicable to autogenous fish biologics, and the Guidelines for Autogenous Veterinary Biologics for Use in Fish (Veterinary Biologics Guideline 3.8 dated June 4, 1997) has been consolidated with this guideline.

In accordance with the Health of Animals Act Section 64.(1)(s), veterinary biologics must be shown to be pure, potent, efficacious and safe. However, during an emergency, data to demonstrate potency and efficacy may be exempted under Section 131.1 (1) of the Health of Animals Regulations. Autogenous veterinary biologics may be approved to meet a specific and immediate need when a disease is associated with a new pathogenic organism, when approved veterinary biologics are not effective in controlling the current disease problem, or when approved veterinary biologics are not available to prevent or control the disease situation.

Use of infected tissue, blood, serum or faeces from sick or dead animals in healthy animals and use of bedding materials from contaminated premises at another premise is considered unacceptable from a veterinary biosecurity perspective. This practice is in violation of Health of Animals Regulations Part X Sections 112 and 113.1.

This guideline has been revised to explain the requirements for autogenous veterinary biologics in more detail and no major changes to these requirements have been made. The requirements outlined in this guideline must be implemented immediately.

Note: In the case of fish, a herd or a flock in this guideline means a population of fish sharing a common watershed and a premise means a hatchery or a body of water of a fish farm.

II. Legal Authority

The authority for regulating veterinary biologics, including autogenous veterinary biologics, is provided in the Health of Animals Act and Regulations^{1, 2}. The Canadian Centre for Veterinary Biologics of the Canadian Food Inspection Agency (CFIA-CCVB) is responsible for licensing and regulating veterinary biologics in Canada.

Health of Animals Act,

Section 64. (1) The Governor in Council may make regulations for the purpose of protecting human and animal health through the control or elimination of diseases and toxic substances and generally for carrying out the purposes and provisions of this Act, including regulations:

• Section 64. (1) (s) prohibiting or regulating the importation, preparation, manufacturing, preserving, packing, labelling, storing, testing, transportation, sale, conditions of sale, advertising for sale, use and disposal of veterinary biologics and regulating their purity, potency, efficacy and safety.

Health of Animals Regulations, Part XI,

Section 121. (1) No person shall import a veterinary biologic into Canada unless he does so under and in accordance with a permit issued by the Minister.

Section 123. No person shall prepare, manufacture, preserve, pack, label or test a veterinary biologic unless he does so under and in accordance with an establishment licence issued by the Minister.

Section 124. No person shall manufacture a veterinary biologic unless he does so under and in accordance with a product licence issued by the Minister.

Section 131.1 (1) Where an emergency exists with respect to the availability of and need for a veterinary biologic, the Minister may exempt that veterinary biologic from the application of any of the provisions of these Regulations during the period of the emergency.

Section 131.1 (2) An exemption referred to in subsection (1) shall be in writing and shall state the veterinary biologic that is exempted, the provision or provisions of these Regulations from which it is exempted and the reasons for that exemption.

Section 131.1 (3) The Minister may at any time cancel the exemption referred to in subsection 131.1.(1).

Section 135. (1) No person shall, in any advertisement for the sale of a veterinary biologic, make any claim with respect to the purity, safety, potency and efficacy of the veterinary biologic that is not supported by the product outline for such veterinary biologic.

Section 135. (2) No person shall, in any advertisement for the sale of a veterinary biologic, make any representation that is false, misleading or deceptive or that is likely to create an erroneous impression regarding the character, value, quality, composition, merit or safety of the advertised veterinary biologic.

Section 135.1 Every holder of a licence or permit issued under this Part shall report to the Minister, in writing, any information concerning or any evidence of, a significant deficiency in safety, potency or efficacy or a veterinary biologic within 15 days after the date on which that information or evidence is known to the holder or is generally known to the industry.

III. General Guidance

A. Basic Criteria

• Autogenous biologics are prepared by authorized manufacturers for emergency use by or under the direction of a licensed veterinarian.
• Manufacturers must obtain a written approval for the production of autogenous veterinary biologics from CFIA-CCVB.
• A valid veterinarian-client-patient relationship is a prerequisite for the use of autogenous biologics as each use of an autogenous biologic must be justified based on clinical and laboratory diagnosis and a veterinary prescription.
• Autogenous biologics shall be prepared from the culture(s) of microorganism(s) isolated from the infected animals and judged to be the cause of the current infectious disease affecting the herd, flock, or an individual animal on the premises.
• Autogenous biologics shall consist of cultures or extracts of microorganisms that are inactivated and nontoxic. The production and use of an autogenous biologic containing live microbial organisms or an autogenous biologic containing viral and bacterial combinations is not permitted.
• Autogenous biologics are to be used only in the herd or flock of origin unless justified by the attending licensed veterinarian as described under Section IV.E.
• Autogenous biologics must be considered safe for the target and non-target animals, humans, and the environment.
• Only the amount of autogenous biologic needed for primary and booster vaccinations of the herd or flock of origin within a year shall be produced. Any autogenous biologic left over after final vaccination must be destroyed.
• Potency and efficacy of autogenous biologics are not established.
• Due to lack of efficacy and potency data, the expiration date for the autogenous biologic shall not exceed twelve months from the date of harvest and the extension of expiration dating is not permitted.
• No autogenous biologics will be permitted against the diseases that are regulated by CFIA under its disease control or eradication program.
• Applications for production and use of autogenous biologics against certain diseases may be evaluated in consultation with other relevant authorities of CFIA and other departments and agencies.
• The materials of animal origin used in the isolation of seed materials, and preparation and testing of an autogenous biologic must comply with Veterinary Biologics Guideline 3.32 (Guideline for Minimising the Risk of Introducing Transmissible Spongiform Encephalopathy Agents Through Veterinary Biologics³).

B. Roles and Responsibilities of the Attending Veterinarian

The attending veterinarian will be responsible for:

• ensuring a proper veterinarian-client-patient relationship;
• coordinating disease diagnosis, isolation and identification of causative organism;
• issuance of a prescription for an autogenous biologic and completing and signing the required form describing the specific disease problem, including names, addresses and phone numbers of the owner, date of the disease outbreak, animal species and number of animals affected, tentative diagnosis, dates of specimen collection and/or isolation of the causative agent, and rationale for use of autogenous biologic (Refer to Appendix III);
• maintaining records of prescriptions and use of autogenous biologics;
• administration of the autogenous biologics under his/her directions;
• in the case of imported autogenous biologics, maintaining a copy of the import permit and complying with all conditions noted on the import permit;
• reporting suspected adverse reaction due to autogenous biologics to the manufacturer and/or CFIA-CCVB.

C. Roles and Responsibilities of the Manufacturer

The manufacturer will be responsible for:

• preparation of microbial seeds for the production of autogenous biologics;
• ensuring the purity and identity of seed materials;
• production, testing, packaging, labelling, storage and distribution of autogenous biologics in accordance with the Health of Animals Acts and Regulations, this guideline, Veterinary Biologics Establishment Licence, Veterinary Biologics Product Licence and approved Outline Production (OP) and associated Special Outlines (SO);
• ensuring that each serial of autogenous biologic has been evaluated for purity, sterility and safety prior to its use;
• maintaining appropriate records as described under section IV.M;
• retaining samples of each serial of autogenous biologics for confirmatory testing when requested by CFIA-CCVB;
• reporting any suspected adverse reaction due to autogenous biologics to CFIA-CCVB in accordance with the Health of Animals Regulations Part XI Section 135.1.

IV. Production of Autogenous Veterinary Biologics

A. Facility and Personnel Requirements

1. The facility, personnel and equipment must be suitable for manufacturing, preservation, packaging, labelling, testing, storage and distribution of veterinary biologics as per the Health of Animals Regulations (Section 128).
2. The facility must be inspected by a CFIA veterinary inspector and approved by CFIA-CCVB prior to production of autogenous biologics.
3. Microbial seeds used for the production of autogenous veterinary biologics cannot be introduced into non-autogenous veterinary biologics manufacturing facilities. The autogenous biologics manufacturing facility must be separated from the laboratories where diagnostic and research activities are carried out.
4. Each serial of the autogenous biologics must be prepared on a campaign basis.

B. Data and Documentation Requirements

The following is a general list of documents required for approval of an autogenous biologic. Refer to New Product Submission Checklist For Autogenous Vaccines available on CFIA-CCVB website. Each application is reviewed on a case-by-case basis and additional information may be requested at the time of review:

1. a cover letter introducing the submission and identifying the regulatory contact for CFIA-CCVB;
2. Application For Services (Form CFIA/ACIA 4720) with appropriate fee⁴ (See Appendix I);
3. Veterinary Biologics Information (Form CFIA/ACIA 1503);
4. two signed copies of generic OP for the autogenous biologics that require similar materials and methods for production and testing. A separate OP will be required for each autogenous biologic, if the production and testing methods differ significantly from the generic OP. See Section IV.H for specific requirements for autogenous killed virus vaccines;
5. two signed copies of each SO (i.e. test methods for sterility, safety, inactivation, residual formaldehyde etc.);
6. information on materials of animal origin used for isolation of seed materials, and production and testing of autogenous biologics (Refer to Veterinary Biologics Guideline 3.32: Guideline for Minimising the Risk of Introducing Transmissible Spongiform Encephalopathy Agents Through Veterinary Biologics³);
7. Declaration of Compliance for materials of animal origin;
8. a copy of sample Manufacturer's Serial Release Test Report (MSRTR) (Refer to Appendix II). A sample copy of MSRTR is not required from the manufacturers in the United States;
9. adjuvant safety data for autogenous biologics containing an adjuvant;
10. validation data to support materials and methods of inactivation indicated in OP or SO;
11. two sets of container labels and package insert as described under IV.C below;
12. additional information, as deemed necessary by the manufacturer and CFIA-CCVB.

C. Labelling of Autogenous Veterinary Biologics

The labelling for autogenous biologics must contain the information as listed below. A generic label containing the information listed under items 1, 4, 9 and 10 must be submitted with the initial application. Depending on the size of the final container, some of the information may be included in the package insert (Refer to Veterinary Biologics Guideline 3.3: Guideline for Labelling of Veterinary Biologics⁵):

1. assigned name of the product (for example, for bacterial product, Autogenous Bacterin followed by the name of the bacteria, or for viral product, Autogenous Vaccine followed by the name of the virus and the term “Killed Virus”). A trade name is not permitted for an autogenous biologic;
2. species of animal in which the autogenous biologic will be used;
3. name and address of the attending licensed veterinarian;
4. name, address and establishment licence number of the manufacturer;
5. preservatives and inactivating agents used in the autogenous biologic;
6. net quantity (volume or doses) in the container;
7. expiration date and serial number of the product;
8. dosage, recommended route of administration, frequency of vaccination and withdrawal period;
9. storage conditions;
10. the label and package insert must include the following standard cautionary statements:
    "For veterinary use only. For vaccination of healthy animals against disease(s) caused by ... [name(s) of the organism(s)]. Do not vaccinate within 21 days (or more depending on the type of the adjuvant used) before slaughter. An autogenous biologic is used in an emergency situation when a licensed product is not available to prevent the spread of a disease to healthy animals. Potency and efficacy of this biologic have not been established. This product has been prepared for use only by or under the direction of a licensed veterinarian.”
11. additional cautionary statements or warnings as required.

Upon review and approval of the materials described in Section IV.B and IV.C above, a Veterinary Biologics Product Licence for a generic autogenous bacterin or a specific autogenous viral vaccine will be issued to the Canadian manufacturer.

For approval process of autogenous veterinary biologics manufactured in the U.S., see Section IV.K.

D. Requirements for Production and Use of Multivalent Autogenous Biologics

Ordinarily, autogenous biologics shall be monovalent. However, an autogenous biologic containing multiple organisms may be prepared and used at the discretion of the attending licensed veterinarian. All production and use of autogenous biologics containing multiple organisms must be justified in writing. An autogenous biologic shall contain only the organisms which are isolated from the same herd or flock, and are considered to be the cause of the current disease situation. Since the data to support lack of antigenic interference is not available for autogenous biologics, the number of antigenic fractions contained in an autogenous biologic must be minimized as much as possible. The risk of adverse reactions due to a multivalent autogenous biologic must also be considered.

A separate approval is not required from CFIA-CCVB for the production of a multivalent autogenous biologic. However, a copy of the written justification from the attending veterinarian must be maintained in the batch file and made available to a CFIA veterinary inspector when requested. The approved OP must describe the materials and methods used in production and testing of all antigens of a multivalent autogenous biologic.

Autogenous biologics must not be mixed with licensed products because there are no supporting data to evaluate the impact of the autogenous product on the safety and efficacy of the licensed product.

E. Requirements for Production and Use of Autogenous Biologic in Adjacent and Non- adjacent Premises

Autogenous biologics are to be used only on the premises from which the microorganism was isolated. At the discretion of the attending licensed veterinarian, an autogenous biologic may be used in adjacent premises if the animals at the adjacent premises are considered to be at risk. Only the isolate from the recent outbreak of infectious disease shall be used.

An autogenous biologic may be used at non-adjacent premises only with a valid justification from the attending licensed veterinarian. The veterinarian must clearly identify the common links or sources that could potentially transmit the disease between the herd of origin and the non-adjacent premises.

A separate approval is not required from CFIA-CCVB for use of an autogenous biologic in adjacent and non-adjacent herds. However, a copy of the written justification from the attending veterinarian must be maintained in the batch file and made available to a CFIA veterinary inspector when requested.

F. Requirements for Production and Use of Autogenous Biologics in the Second Year

The production and use of autogenous biologics from the same isolate for the second year must be justified with supporting data (confirming the clinical and laboratory diagnosis and significant benefit from the previous use of the autogenous biologics) by the attending licensed veterinarian. A separate approval is not required from CFIA-CCVB for production and use of an autogenous biologic in the second year. However, a copy of the written justification from the attending veterinarian must be maintained in the batch file and made available to a CFIA veterinary inspector when requested.

G. Requirements for Production and Use of Autogenous Biologics beyond the Second Year

The long term use of the same isolate for production and use of an autogenous biologic is not considered an emergency under Section 131.1 (1) of the Health of Animals Regulations. Therefore, the use of the same isolate for production of autogenous biologics beyond the second year is not permitted without additional supporting data on purity, safety, potency and efficacy. All requests for the use of an isolate beyond the second year are reviewed by CFIA-CCVB on a case-by-case basis.

To approve the same isolate for production of autogenous biologics beyond the second year, the microbial seed (bacteria or virus ) must be tested for identity and extraneous agents, and an efficacy study must be performed to establish the appropriate potency of a particular autogenous biologic. The required number of representative samples from each seed and serial of autogenous biologics must be submitted to the Biologics Evaluation Laboratory (BEL) for confirmatory testing and two copies of MSRTR must be submitted to CFIA-CCVB⁶. Each serial of autogenous biologics prepared from the same isolate beyond the second year will be released by CFIA-CCVB after satisfactory review of MSRTR and BEL report.

Refer to Appendix I for the fees for confirmatory testing of microbial seed and serial release.

H. Specific Requirements and Restrictions for Production and Use of Autogenous Killed Viral Vaccines

Unlike autogenous bacterins, a separate submission is required for each autogenous killed virus vaccine. The OP must describe the specific materials and methods used in the production and testing of each autogenous killed virus vaccine. Each application for an autogenous killed virus vaccine is reviewed on a case-by-case basis.

In addition to the documents listed under Section IV.B (for Canadian manufacturers) and Section IV.K (for the US manufacturers), an application for autogenous killed virus vaccine shall include:

• two signed copies of OP describing the specific materials and methods used in the production and testing of each autogenous killed virus vaccine;
• data on cell lines and embryonated eggs:
  • Cells: The primary cells and the established cell lines used in the production of an autogenous vaccine must meet the same requirements as a fully licensed vaccine, including confirmatory testing by BEL⁶.
  • Embryonated eggs: The embryonated eggs used for autogenous biologics must be obtained from an acceptable supplier of specific pathogen free (SPF) eggs. The source of the SPF eggs must be identified in the OP.
• data on virus seed:
  • Virus seed for the first two years: The virus seed used for an autogenous killed virus vaccine must be tested for identity. Submission of virus seed sample to BEL is not required for the first two years.
  • Virus seed after two years: In addition to identity, the virus seed used for an autogenous killed virus vaccine beyond the second year must be tested for extraneous agents. The required number of samples of this virus seed must be submitted to BEL for confirmatory testing⁶.

I. Serial Release Procedure for Autogenous Biologics, Including Autogenous Killed Viral Vaccines

First two years:

The required quantity of representative samples from each serial must be collected for testing by the manufacturer and for retention by the manufacturer for BEL testing. Manufacturers are not required to submit the samples from serials prepared within the first two years to BEL, unless requested by CFIA-CCVB.

Each serial of autogenous biologics must be tested for sterility, safety, completion of inactivation, residual formaldehyde (if applicable), and any other tests as specified in the approved OP. All required tests must be completed satisfactorily and documented in MSRTR before releasing the serial for shipment. A satisfactory serial can be released by the quality control or quality assurance supervisor of the manufacturer.

Beyond the second year:

In addition to the tests specified for the first two years, all serials prepared after the second year must be tested for potency. The required number of samples from each serial must be submitted to BEL for confirmatory testing and two copies of MSRTR must be submitted to CFIA-CCVB⁶. All serials prepared from the same isolate after two years will be released by CFIA-CCVB after satisfactory review of the MSRTR and BEL report.

Refer to Appendix I for the fees for serial release.

J. Requirements for Production of Autogenous Biologics for Export to Foreign Countries

A new serial of autogenous bacterins may be prepared for export to a foreign country (including the US) under the manufacturer's existing product licence with the conditions listed below.

Requests for production of an autogenous killed virus vaccine for export to foreign countries will be reviewed on a case-by-case basis and the specific requirements will be identified during the review of the application:

1. A written authorization from the regulatory authority of the importing country and CFIA-CCVB must be obtained prior to initiating the production activity of a new serial of autogenous bacterin intended for export.
2. The seed material imported into Canada must be in the form of pure culture and not in the form of animal tissue or body fluid. The Canadian manufacturer importing the seed materials must contact the Office of the Biohazard Containment and Safety of CFIA for the specific requirements for import permit for animal pathogens.
3. The seed culture must be tested to confirm the identity of the organism and purity of the culture. The seed culture must be found to be pure prior to introduction into the autogenous biologics production facility.
4. Production of autogenous biologics against animal pathogens which are not prevalent in Canada or diseases exotic to Canada is not permitted.
5. The materials and methods used in the production and testing of the export serial must conform with the materials and methods described in the OP for autogenous bacterins on file with CFIA-CCVB. The manufacturer will be required to revise the current OP and/or submit new OP and SO, if the materials and methods used in the production and testing of the export serial vary from the generic OP or SO filed with CFIA-CCVB. The new or revised OPs and SOs must be approved by CFIA-CCVB before the production of the export serial.
6. All materials of animal origin used in the production and testing of the export serial must conform with the requirements described in Veterinary Biologics Guideline 3.32.
7. The total volume or doses of the serial must be as specified in the official document issued by the regulatory authority of the importing country.
8. Multiple serials or sub-serials from the same seed may be prepared to complete the volume or doses specified in the initial permit or official document issued by the regulatory authority of the importing country. Similarly, additional serials or sub-serials may also be prepared from the same seed to export additional shipments if authorized by the regulatory authority of the same country through an amended or new official document. The official document must be maintained by the manufacturer to justify the production and export of multiple serials or sub-serials.
9. A serial or sub-serial of an autogenous bacterin prepared for export to one country cannot be exported to a second country without written approval from the destination country as well as from CFIA-CCVB.
10. A new serial of an autogenous bacterin can be shipped only after all tests (including, completion of inactivation, sterility and animal safety test) are completed satisfactorily.
11. The label used for the autogenous bacterin may be prepared as per the requirements and in the language of the importing country. However, the label must clearly identify the product as an autogenous veterinary biologic showing the name of the organism, target animal species, net quantity in the container (volume or doses), storage conditions, dosage, serial number, expiration date, name and address of the manufacturer, and Canadian Veterinary Biologics Establishment number. In order to prevent any inadvertent use of the product in Canada, the label must include a statement “For use in [name of the country] only” or “Not for use in Canada” or another equivalent statement.
12. The manufacturer will be responsible for complying with the national, provincial and local regulations of the importing country, and any conditions or restrictions specified by the regulatory authority of the importing country.
13. Accurate, complete and current records of production, testing, shipping and receiving of all starting materials, bulk antigens and finished product must be maintained by the manufacturer and made available to a CFIA veterinary inspector when requested.

Procedure for Obtaining Written Approval from CFIA-CCVB for Production and Shipment of Autogenous Bacterins to Foreign Countries:

The manufacturer will require written approval from CFIA-CCVB prior to production of a new serial of autogenous biologics for export to a foreign country. To obtain an approval for the production of a new serial of an autogenous biologic for export, the Canadian manufacturer must submit the following documents to CFIA-CCVB for review:

1. a cover letter identifying the name of the organism and number of doses/volume to be produced, and a statement confirming that the production and shipment of the new serial of the autogenous bacterin will conform with the specific conditions listed under Item IV.J of this guideline;
2. a copy of the official document (i.e., permit, licence, certificate or equivalent) issued by the regulatory authority of the importing country showing the name of the organism and number of doses/volume to be exported;
3. a copy of the certified translation, if the official document is not in English or French;
4. a copy of the laboratory report confirming purity of the culture and identity of the organism.

After the receipt and satisfactory review of the above documents, CFIA-CCVB will authorize the introduction of the seed into autogenous biologics production facility for production of a new serial of autogenous bacterin through a letter. There is no cost recovery fee associated for this service at this time, therefore, an Application for Service (Form CFIA/ACIA 4720) is not required.

K. Requirements for Importation of Autogenous Biologics from the United States

The approval of the autogenous biologics manufactured in the U.S. is a two-step process.

First, the U.S. manufacturer must satisfy the data and documentation requirement concerning the manufacturing facility and materials and methods used in production and testing of the autogenous biologics. The U.S. manufacturing facility may be inspected by a CFIA veterinary inspector before the approval of the autogenous biologic.

In addition to the requirements listed under Section IV.B (for autogenous bacterin) and Section IV.H (for autogenous killed virus vaccine), manufacturers in the U.S. are required to submit the following materials:

• a copy of the US Veterinary Biologics Establishment License;
• a copy of the US Veterinary Biological Product License;
• a copy of the USDA-CVB approved Outline of Production and SOs;
• a copy of the USDA-CVB approved label and package insert;
• a set of facility and personnel documents;
• a copy of the latest inspection report of USDA-CVB.

The approval of the submitted materials allows the U.S. manufacturers to prepare autogenous biologics for the attending veterinarians in Canada in accordance with the specific conditions or restrictions identified at the time of the approval.

The second step of the approval process involves submission of the following documents to support the application for a permit to import a specific serial of autogenous biologic by the attending veterinarian:

1. a completed Application for Services (Form CFIA/ACIA 4720) with the appropriate fee (See Appendix I);
2. an Application for Permit to Import Veterinary Biologics (Form CFIA/ACIA 1493) signed by the attending veterinarian;
3. a completed and signed form describing the specific disease problem, including names, addresses and phone numbers of the owner and attending veterinarian, date of the disease outbreak, animal species and number of animals affected, tentative diagnosis, dates of specimen collection and/or isolation of the causative agent, rationale for use of the autogenous biologic and a copy of the laboratory report (Refer to Appendix III for the required form);
4. summary of test results (Form APHIS 2008) for the serial of autogenous biologic to be imported;
5. a copy of the label that will be used for the serial intended for use in Canada showing the name and address of the attending licensed veterinarian, serial number and expiration dating. The expiration date for the autogenous biologic manufactured for distribution in Canada shall not exceed twelve months from the date of harvest;
6. results of completion of inactivation test for autogenous killed virus vaccine;

Each request for production and importation of autogenous biologics from the U.S. is reviewed on a case-by-case basis and additional information may be requested at the time of review. Upon approval of the application, a single entry Permit to Import Veterinary Biologics will be issued to the Canadian veterinarian for a specific serial of the autogenous biologic. A copy of the permit must be kept on file by the attending veterinarian and a copy of the permit must accompany each shipment.

For a serial of an autogenous killed virus vaccine, the Canadian importers are required to submit Items 1, 2, and 3 to CFIA-CCVB prior to placing their order with the US manufacturer. Items 4, 5, and 6 can be submitted directly by the manufacturer when the tests are completed.

L. Requirements for Manufacturers in Countries other than the U.S.

The manufacturers in other countries must meet all the regulatory requirements as specified in this guideline. The facility must be inspected and approved by CFIA-CCVB prior to production of a serial of an autogenous biologic for use in Canada. Each application for licensing and importation of an autogenous biologic from other countries will be reviewed on a case-by-case basis.

M. Record Keeping

The following records for each serial of autogenous biologics must be maintained by the manufacturers and made available to a CFIA veterinary inspector when requested:

• Signed veterinary prescription for each serial of an autogenous biologic.
• Information about the specific disease problem as described under Sections III.B and IV.K.3. This information is normally provided by the attending licensed veterinarian.
• Microorganism isolation and laboratory test report.
• Isolate/seed inventory record with all isolates listed by their unique ID number.
• Accurate, complete and current production and testing records (including a completed and signed MSRTR or APHIS 2008 showing all in vitro and target animal or laboratory animal safety tests).
• Inventory and distribution record for each serial.
• Copy of the label used for each serial.
• Records of any suspected adverse reactions.
• Written justification from the attending veterinarian for the following circumstances:
  • using the same isolate in production of a new serial of autogenous biologics for the second year;
  • preparing multivalent autogenous biologics;
  • preparing the same autogenous biologic for adjacent and non-adjacent herds.

N. Restrictions on Advertisement of Autogenous Biologics

The authority for regulating the advertisement of veterinary biologics is provided in the Health of Animals Regulations, Part XI Section 135. (1) and 135. (2). Manufacturers of autogenous biologics may advertise their services for the purpose of informing Canadian veterinarians. However, any specific autogenous biologics or any claim against specific disease (including potency and efficacy) must not be advertised, due to the lack of data to support purity, potency, field safety and efficacy, otherwise it will contravene Sections 135.(1) and 135.(2) of the Health of Animals Regulations, which require all advertised claims to be supported by data on file with CFIA-CCVB.

O. Miscellaneous

Any other issues or situations that are not covered in this guideline may be reviewed by CFIA-CCVB on a case-by-case basis.

V. Further Information

Any further questions or clarification regarding regulations and requirements pertaining to autogenous biologics may be obtained from the Canadian Centre for Veterinary Biologics (see Contacts, Canadian Centre for Veterinary Biologics).

Guidelines and forms are available at the CFIA-CCVB website.

VI. References

1. Health of Animals Act, Section 64 (1) (s);
2. Health of Animals Regulations, Part XI, Sections 120 - 135;
3. Veterinary Biologics Guideline 3.32 (Guideline for Minimising the Risk of Introducing Transmissible Spongiform Encephalopathy Agents Through Veterinary Biologics);
4. National Animal Health Program Cost Recovery Fees Order - Part VI, Services Related To Veterinary Biologics;
5. Veterinary Biologics Guideline 3.3 - Guidelines for Labelling of Veterinary Biologics;
6. Veterinary Biologics Guideline 3.22 - Guidelines for submission, Testing and Reporting of Biological samples.

VII. Appendices

Appendix I

The fee schedule for autogenous biologics for Canadian manufacturers as listed under 'Summary of Fees and Services Related to Veterinary Biologics (Form CFIA/ACIA 5189) is as follows:

Project Code #	Description	Fee ($)	GST 5%	Total ($)
1362	Filing and preliminary review of application	200	10	210
1363	Evaluation of the application	450	22.50	475.50
1364	Issuance of a product licence	200	0	200
1371	Annual renewal of the product licence	120	6	126
1384	Testing of each master cell line	700	35	735
1385	Testing of each master seed culture*	550	27.50	577.50
1373	Application for serial release*	150	0	150
1376	Revision to production outline or labelling	60	3	63

* Applies to serials of autogenous biologics prepared beyond the second year (See Section IV.I of this guideline)

The fee schedule for autogenous biologics manufactured in the United States as listed under 'Summary of Fees and Services Related to Veterinary Biologicsis (Form CFIA/ACIA 5189) as follows (the fees are shown in Canadian dollars):

Project Code #	Description	Fee ($)	GST 5%	Total ($)
1343	Filing and preliminary review of application	200	10	210
1344	Evaluation of the application	450	22.50	475.50
1345	Issuance of a product licence	200	0	200
1346	Annual renewal of the product licence	60	0	60
1384	Testing of each master cell line	700	35	735
1385	Testing of each master seed culture*	550	27.50	577.50
1373	Application for serial release*	150	0	150
1376	Revision to production outline or labelling	60	3	63

* Applies to serials of autogenous biologics prepared beyond the second year (See Section IV.I of this guideline)

Please refer to 'Summary of Fees and Services Related to Veterinary Biologicsis⁴ (Form CFIA/ACIA 5189) for additional fees, such as fees for facility inspection and establishment licence.

Appendix II

Sample of Manufacturer's Serial Release Test Report (MSRTR) for Autogenous Biologic

Name of the Company:
Canadian Veterinary Biologic Establishment Licence N^o.
Telephone:
Fascimile:

Product name:

CCVB File N^o.:
Production Outline dated:
Animal Species:
Name and address of the farm:

Serial N^o.:
Unique ID of isolate:
Filling date:
Expiration date:
Container size:
Total number of containers:
Total number of doses:

Name and address of the veterinarian:

Test & Reference	Start date yyyy/mm/dd	End date yyyy/mm/dd	Test requirement	Test results	Codes*
Purity (pre-inactivation) OP/SO reference
Sterility - bulk product OP/SO reference
Sterility - finished product OP/SO reference
Animal safety OP/SO reference			Species and number of animals tested:
Residual formaldehyde OP/SO reference
Other tests (specify) OP/SO reference

* Codes: S=Satisfactory; U=Unsatisfactory; I=Inconclusive; NT=No test or invalid test

Disposition by manufacturer:

All tests completed satisfactory (Yes or No):
Eligible for release (Yes or No):
Destroyed (If yes, reasons for destruction):
Additional comments (if applicable):

(Note: The corresponding bench records for in-process and final product tests for each serial must be maintained on file, refer to Section IV.M of this guideline)

Appendix III

Information Required for Autogenous Veterinary Biologics

For additional information, see CFIA Veterinary Biologics Guideline 3.13: Autogenous Veterinary Biologics

1. Attending veterinarian information

2. Farm Information

Location of premises where autogenous veterinary biologic will be used (attach a list if multiple premises):

3. Animal Information

Vaccination plans and total doses of vaccine required:

4. Description of disease problem and rationale for using autogenous vaccine (Please attach extra sheets if necessary)

Briefly describe the disease problem, tentative diagnosis of causative agent(s), and rationale for use of autogenous biologic. To support rationale for use of autogenous biologic, provide information on commercial vaccine(s) used, or considered for use, to address the disease situation. Indicate if an autogenous biologic was previously used to address this situation (if yes, identify organism genus and species, source of isolate (owner, premises), and date of isolation):

5. Microorganism Information

Name of the diagnostic laboratory and diagnostician (include a copy of laboratory report confirming identity of vaccine seed organism):

The owner has been advised that autogenous veterinary biologics are intended for use as an interim measure in emergency situations when a suitable licensed product is not available to prevent the spread of a disease within the animals, birds, or fish on the infected premises, and other associated premises where the autogenous veterinary biologic will be used. The undersigned veterinarian and client are aware that the potency and efficacy of this veterinary biologic have not been established, and that this product has been prepared for use only by, or under the direction of, a licensed veterinarian.