RFP 01B68-13-0068 Appendix D Annex 1
Veterinary Drugs Human Safety – Residue Depletion Trials Application Form
PEST MANAGEMENT CENTRE – Veterinary Drugs Initiative
Human Safety - Residue Depletion Trial Application Form
The purpose of the residue depletion trials is to quantify residue concentrations of marker residue in rabbit tissues after administration of
proposed label doses of drugs. The tissue residue depletion data will be used by the Veterinary Drugs Directorate, Health Canada to calculate
an appropriate withdrawal period after label use of the drug in rabbits (Annex 1, Table 1).
The purpose of this template is to provide applicants with the “key elements” of a well-structured residue depletion trial protocol, such that
meaningful safety data are generated. It is recommended that applicants submit a description of the planned protocol for each element listed.
Alternate approaches to the principles described in this document may be acceptable provided they are supported by adequate scientific
justification.
The objective of the application form is to guide bidders in the preparation of their bid and to provide AAFC with a tool to better assess,
evaluate, and contrast the proposals submitted. It’s very important to fully complete every field. By having this template in MS Word allows
bidders to adjust the space in each field according to the size of information used to fulfill / address the template requirements.
COMPLETE ONE HUMAN SAFETY - RESIDUE DEPLETION TRIAL APPLICATION FORM FOR EACH TRIAL FOR
WHICH YOU ARE MAKING A BID. Submit hard copies of each form with your proposal as indicated in the Request for Proposals
01B68-0068. It is not necessary to submit reference letters and general company information with each application form (one set of each per
proposal copy is sufficient).
HUMAN SAFETY - RESIDUE DEPLETION TRIAL APPLICATION FORM
Trial number:
Test animal:
Authorized Medicated Premixes* (product name and DIN):
Target dosage and duration:
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RFP 01B68-13-0068 Appendix D Annex 1
Veterinary Drugs Human Safety – Residue Depletion Trials Application Form
Name of Organization:
Mailing Address:
Contact person
Name/Title:
Tel:
E-mail:
Fax:
Study Monitor details:
Name:
Tel:
Fax:
E-mail:
Principal Investigator details:
Name:
Tel:
Fax:
E-mail:
HUMAN DEPLETION - RESIDUE DEPLETION TRIAL APPLICATION FORM
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RFP 01B68-13-0068 Appendix D Annex 1
Veterinary Drugs Human Safety – Residue Depletion Trials Application Form
HUMAN DEPLETION - RESIDUE DEPLETION TRIAL APPLICATION FORM
Objective
The applicant should specify the primary objective of the residue depletion trial
i.e., drug product to be tested and dosage. For reference, some information is
provided in Annex 1 however, alternate dosage and/or other approved products
may be acceptable provided they are supported by adequate rationale.
Experience in the conduct of veterinary drugs residue depletion trials
Provide evidence (by way of a minimum of two letters of reference) of having
completed a minimum of three residue depletion trials in a satisfactory manner
Reference letters should demonstrate work experience that is clearly related to
the projects described. References must include the name of the organization
for whom the work was done, the name of the individual who was the project
authority or equivalent, their phone number, fax, mailing and email addresses.
Study Facility.
Provide evidence that a facility where the in-life phase of the study has been
identified, and secured.
GLP compliance.
The applicant must identify a GLP-compliant laboratory which is capable of
quantifying the drug residue concentrations in rabbit tissues. The assay used
by the contract laboratory must be validated, including matrix validation in
rabbit tissues. Copy of GLP certification must be provided.
Key participants
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RFP 01B68-13-0068 Appendix D Annex 1
Veterinary Drugs Human Safety – Residue Depletion Trials Application Form
HUMAN DEPLETION - RESIDUE DEPLETION TRIAL APPLICATION FORM
The applicant should provide a full list of key study participants, including
résumé, experience and publications for each study investigator.
In-life phase
Study facility: The facility where the in-life phase of the study
should be identified, and should be appropriate for such
studies.
Test Animals.
The breeds, ages, and sex of rabbits used in the residue
depletion studies should be consistent with those likely to be
treated on Canadian farms.
Inclusion/exclusion criteria for test animals should be
identified. Conditions (e.g., health conditions, adverse events
etc.) that may need to exclude an animal from the trial should
be considered.
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RFP 01B68-13-0068 Appendix D Annex 1
Veterinary Drugs Human Safety – Residue Depletion Trials Application Form
HUMAN DEPLETION - RESIDUE DEPLETION TRIAL APPLICATION FORM
Drug treatment: Rabbits in the residue depletion should
receive the test compound in a manner consistent with
Canadian rabbit husbandry conditions (i.e., oral
administration in feed, as opposed to gastric lavage). The dose
and duration of treatment are identified for each drug in Table
1 (under Human Safety). For a drug that will qualify for a 0day withdrawal period, the dose used should be 1.5x to 2x the
recommended dose for maximum duration of treatment. Rabbits
cannot receive concurrent administration of other veterinary
drugs which may interfere with the absorption, metabolism, or
excretion of the compound of interest, or may interfere with the
analytical method used to quantify the residues.
Animal husbandry: Animal management should be to the
extent possible consistent with commercial Canadian rabbitry
conditions with proper considerations for animal welfare.
Feeds should be appropriate for the age. Nominal and actual
concentration of the drug in medicated feed, and the date and
time medicated feed was introduced and withdrawn should be
recorded.
Daily feed offered and consumed should be recorded for each
animal to determine the nominal and actual dose administered
Any adverse health effects on animals during the treatment
period should be recorded, and assessed to determine if it may
have an impact on incurred residues
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RFP 01B68-13-0068 Appendix D Annex 1
Veterinary Drugs Human Safety – Residue Depletion Trials Application Form
HUMAN DEPLETION - RESIDUE DEPLETION TRIAL APPLICATION FORM
Animal numbers: A minimum of 20 rabbits should be utilized
in the residue depletion study. Groups of 4 – 5 rabbits should
be euthanized at various time points following the cessation of
treatment. The slaughter time interval should be equally
spaced, and encompass the expected withdrawal period for the
drug. Applicants should justify the proposed sampling periods
based on published pharmacokinetic data and assay sensitivity.
If the drug qualifies for a 0-day withdrawal, only 10 rabbits
need to be treated at 1.5x to 2x the recommended dose and
maximum duration of treatment, and all animals euthanized at
practical 0-day, which is considered to be 6 hours after the
withdrawal of medicated feed.
Animal management A description should be provided
regarding planned animal management, i.e., feeding,
husbandry, including consideration and all applicable
information to ensure animal welfare during the generation of
information from clinical studies.
Analytical phase
Tissues should be analyzed for the marker residue
concentration using a validated method Applicants will be
requested to provide evidence of assay validation. If the
proposed tissue assay methods have not been validated for use
in rabbit tissues, the applicant should include a summary of the
proposed matrix validation process (including timelines for
completion of validation studies).
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RFP 01B68-13-0068 Appendix D Annex 1
Veterinary Drugs Human Safety – Residue Depletion Trials Application Form
HUMAN DEPLETION - RESIDUE DEPLETION TRIAL APPLICATION FORM
The limits of detection (LOD) and quantification (LOQ) of the
proposed assay should be provided.
Data requirements for all residue depletion trials
Applicants must identify appropriate strategies to record
and assess all deviations from the study plan.
Applicants will provide a copy of the master schedule for
animal phase of the study.
Applicants will be required to submit a final report,
including properly summarized and statistically analyzed
data, including a copy of the raw data from the in-life or
analytical phases of the residue depletion trial (such as feed
consumption data, assay validation reports,
chromatograms, etc.)
Other safety variables
Site health observations, individual animal assessments, body
weights, feed intake
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RFP 01B68-13-0068 Appendix D Annex 1
Veterinary Drugs Human Safety – Residue Depletion Trials Application Form
HUMAN DEPLETION - RESIDUE DEPLETION TRIAL APPLICATION FORM
Final Human Safety - Residue Depletion Report
Data generated should be properly summarized and
statistically analyzed. A final study report signed by all study
participates must be submitted This report should include all
study conclusions and interpretations. The data should be
comprehensively summarized, including the use of tables, and
figures. Individual case reports (i.e., raw data) should be
collated and included at the end of the study report.
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