Guidance Documents...
Primary documents from FDA’s Center for Veterinary Medicine: The following table includes a relatively complete list of guidance documents that CVM makes available to assist the aquaculture industry, the pharmaceutical industry, animal health practitioners, animal owners and caretakers, and other interested parties in making informed decisions on the use of drugs and the generation of information applicable to applications for new animal drug approvals (NADAs). The following table includes those documents referred to as “Guidance for Industry” and sections from CVM’s “Policy and Procedures Manual”.
Guidance
Documents or Policies & Procedures Manual Number |
Title |
| General Principles for Evaluating the Safety of Compounds Used in Food-Producing Animals | |
Guidance
#14 |
Guideline
and Format for Reporting the Details of Clinical
Trials Using An Investigational New Animal
Drug in Food Producing Animals (withdrawn
12/22/2004) |
Guidance
#15 |
Guideline
For Reporting The Details Of Clinical Trials
Using An Investigational New Animal Drug(s)
In Non-Food Producing Animals (withdrawn
12/22/2004) |
Guidance#16 |
Freedom
Of Information Summary Guidelines (withdrawn 02/24/2005) |
Guidance
#33 |
Target Animal Safety Guidelines for New Animal Drugs (replaced by Guidance #85 on 4/24/09) |
Guidance
#41 |
Draft
Guideline: Formatting, Assembling, and Submitting
New Animal Drug Applications (withdrawn 3/2002) |
Series
of four guidelines entitled "Animal
Drug Manufacturing Guidelines" |
|
Guideline
for the Evaluation of the Utility of Food
Additives in Diets Fed to Aquatic Animals |
|
Protocol
Development Guideline for Clinical Effectiveness
and Target Animal Safety Trials |
|
Master Files: Guidance for Industry for the Preparation and Submission of Veterinary Master Files |
|
FDA
Approval of New Animal Drugs for Minor Uses
and for Minor Species - Part 2E: Aquatic
Species |
|
| Validation of Analytical Procedures: Methodology: Final Guidance | |
Guidance
#71 |
Use
of Human Chorionic Gonadotropin (HCG) as
a Spawning Aid for Fish, (rescinded 2/23/2000) |
Guidance
#78 |
Consideration
of the Human Health Impact of the Microbial
Effects of Antimicrobial New Animal Drugs Intended
for Use
in Food-Producing Animals (replaced by Guidance
#152) |
Development
of Supplemental Applications for Approved New Animal Drugs |
|
Good
Clinical Practices: VICH GL9, Final Guidance |
|
| Environmental Impact Assessments (EIA's) for Veterinary Medicinal Products (VMP's) - Phase I - VICH GL6 - Final Guidance | |
The
Use of Published Literature in Support of New Animal Drug Approval |
|
| Safety Studies for Veterinary Drug Residues in Human Food: Reproduction Studies - VICH GL22 - Final Guidance | |
| Studies to Evaluate the Safety of Residues of Veterinary Drugs in Human Food: Genotoxicity Testing - VICH GL23 - Final Guidance | |
| Mass Spectrometry for Confirmation of the Identity of Animal Drug Residues - Final Guidance | |
Veterinary
Feed Directive Regulation |
|
The
Administrative New Animal Drug Application Process: Draft Guidance |
|
| Studies to Evaluate the Safety of Residues of Veterinary Drugs in Human Food: Carcinogenicity Testing, VICH GL28, Final Guidance | |
| Studies to Evaluate the Safety of Residues of Veterinary Drugs in Human Food: Repeat-Dose (90-Day) Toxicity Testing - VICH GL31 | |
| Studies to Evaluate the Safety of Residues of Veterinary Drugs in Human Food: Developmental Toxicity Testing - VICH GL32 Final Guidance | |
| Studies to Evaluate the Safety of Residues of Veterinary Drugs in Human Food: General Approach to Testing VICH GL33 | |
Status
of Clove Oil and Eugenol for Anesthesia of
Fish |
|
Evaluating
the Safety of Antimicrobial New Animal Drugs
with Regard to Their Microbiological Effects
on Bacteria of Human Health Concern |
|
Guidance #159 |
Studies to Evaluate the Safety of Residues of Veterinary Drugs in Human Food: General Approach to Establish a Microbiological ADI - VICH GL-36, Final Guidance (no longer available electronically) |
| Studies to Evaluate the Safety of Residues of Veterinary Drugs in Human Food: Repeat-Dose (Chronic) Toxicity Testing, VICH GL-37 | |
| Environmemtal Impact Assessments (EIA's) for Veterinary Medical Products (VMP's) - Phase II; VICH GL38 - Final Guidance (published 9 January 2006) | |
Drug
Substance Chemistry, Manufacturing, and
Controls Information; Draft Guidance |
|
Animal
Drug User Fees and Fee Waivers and Reductions |
|
| Animal Drug Sponsor Fees Under the Animal Drug User Fee Act (ADUFA) | |
Various |
|
Drug
Use in Aquaculture Enforcement Priorities |
|
Extra-label
Use of Approved Drugs in Aquaculture |
|
Drug-Pesticide
Issues |
|
Regulation
of Fish Identification Products |
|
PPM#12400.4240 |
Safe
Levels of Unapproved Drugs in Aquaculture (no longer available electronically) |
Classification
of Aquaculture Species/Population as Food
or Non- food |
|
Use
of Drugs in Outdoor Aquatic Research Facilities |
Compliance Policy Guide (CPG) documents from FDA’s Center for Veterinary Medicine: The CVM produces other publicly available document series intended for select audiences, an example of which is the “Compliance Policy Guide (CPG) Manual.” The following table includes sections of CVM’s “CPG Manual.” The expressed purpose of these CPG sections is “…to provide a convenient and organized system for statements of FDA compliance policy, including those statements which contain regulatory action guidance information. The statements made in the CPG are not intended to create or confer any rights, privileges, or benefits on or for any private person, but are intended for internal guidance.” Click on document number to view actual document.
Document
Number |
Title |
| Compounding of Drugs for Use in Animals | |
| Extra-label Use of Medicated Feeds for Minor Species | |
| Proper Drug Use and Residue Avoidance by Non-Veterinarians | |
| Responsibility for Illegal Drug Residues in Meat, Milk and Eggs | |
| Availability of Bulk Chemicals for Animal Drug Use | |
| Chloramphenicol as an Unapproved New Animal Drug - Direct Reference Seizure Authority | |
| Use of Type A Medicated Article Brand Names in Feed Labels | |
| Direct-Fed Microbial Products | |
| Complete listing of CVM CPG documents |
The Animal Drug User Fee Act of 2003 (ADUFA): The CVM states that “[ADUFA] amends the Federal Food, Drug, and Cosmetic Act (FFDCA) and authorizes FDA to collect fees for certain animal drug applications, and for the establishments, products and sponsors associated with these and previously approved animal drug applications, in support of the review of animal drugs. These additional resources will support FDA’s responsibilities under the FFDCA to ensure that new animal drug products are safe and effective for animals as well as for the public with respect to animals intended for food consumption.” Two key CVM documents, a webpage and a guidance document, provide extensive information about ADUFA and should be consulted for details. Of major importance to the aquaculture industry is the fact that essentially all fees pertaining to aquatic species (which are defined by FDA as minor species) can be waived. However, CVM will only provide a waiver if and when it is requested of them – Guidance Document #170 explains the procedures for obtaining such waiver. Click on document number to view actual document.
Document
Number |
Title |
| Webpage for the Animal Drug User Fee Act of 2003 | |
| Animal Drug User Fees and Fee Waivers and Reductions |
The Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA): The CVM states that “[AMDUCA] allows veterinarians to prescribe extralabel uses of certain approved animal drugs and approved human drugs for animals under certain conditions. Extralabel (or extra-label) use refers to the use of an approved drug in a manner that is not in accordance with the approved label directions. The key constraints of AMDUCA are that any extralabel use must be by or on the order of a veterinarian within the context of a veterinarian client patient relationship, must not result in violative residues in food-producing animals, and the use must be in conformance with the implementing regulations published at 21 CFR Part 530.” The table below summarizes several key sources of information, from CVM and the American Veterinary Medical Association (AVMA)documents, that provide extensive information about AMDUCA and should be consulted for details. In essence, AMDUCA converts (or codifies) what was once a case of regulatory discretion (i.e., it was illegal, but something that CVM would normally choose not to take regulatory action against) into a law, which now means that extra-labeling by veterinarians is legal if conducted per the conditions of the Act. Click on document number to view actual document.
Document
Number |
Title |
| Webpage for the Animal Medicinal Drug Use Clarification Act of 1994 | |
| Code of Federal Regulations covering Extralabel Drug Use in Animals | |
Extra-label
Use of Medicated Feeds for Minor Species |
|
| An Informational Outline of the Animal Medicinal Drug Use Clarification Act (AMDUCA) |
The Animal Drug Availability Act of 1996 (ADAA): The intended purpose of the ADAA is “to amend the Federal Food, Drug, and Cosmetic Act to provide for improvements in the process of approving, [marketing] and using animal drugs.” The ADAA comprises several sections addressing the general theme of facilitating new animal drug approvals, marketing and use. These sections include: 1) evidence requirements for demonstration of the new drug’s effectiveness, 2) limitation regarding residues, 3) the establishment of acceptable tolerance limits of drug residues in imported animal products, 4) the establishment of the “veterinary feed directives” category of drug approvals, and 5) new feed mill licensure requirements. To date, the generation of all accompanying regulations for ADAA has not been fully accomplished, and other related laws and regulations have yet to be passed by Congress, e.g., Minor Use and Minor Species (or MUMS) legislation (see http://www.fda.gov/cvm/index/mums/minortoc.htm for details on MUMS activities). The following table summarizes sources for information about the ADAA and many of the Federal Regulation changes resulting from passage of the ADAA. Click on document number to view actual document.
Document
Number |
Title |
| Webpage for the Animal Drug Availability Act of 1996 | |
| FDA Approval of New Animal Drugs for Minor Uses and for Minor Species - Part 2E: Aquatic Species | |
| “Veterinary Feed Directive” Regulation | |
| Code of Federal Regulations covering “Veterinary Feed Directive Drugs” | |
| Webpage for Medicated Feed Mill License | |
| Code of Federal Regulations for Medicated Feed Mill License | |
| Code of Federal Regulations covering “Substantial Evidence” | |
| Code of Federal Regulations covering “Adequate and Well-controlled Studies” |
Environmental Impact Considerations: The FDA, as it enforces the Federal Food, Drug and Cosmetic Act, must also comply with environmental laws defined within the National Environmental Policy Act. A required component of every new animal drug application (NADA) submitted to FDA, including those for aquaculture species, must demonstrate that the use of the subject drug will be safe to the environment. The regulations, which spell out what FDA must require to be in an NADA, are contained in the following Code of Federal Regulation (CFR) citations. The regulations are quite extensive, and are, hence, divided into several subparts. Click on document number to view actual document.
Document
Number |
Title |
| 21CFR25.1 – 25.10 | Subpart A – General Provisions |
| 21CFR25.15 – 25.22 | Subpart B – Agency Actions Requiring Environmental Consideration |
| 21CFR25.30 – 25.34 | Subpart C – Categorical Exclusions |
| 21CFR25.40 – 25.45 | Subpart D – Preparation of Environmental Documents |
| 21CFR25.50 – 25.52 | Subpart E – Public Participation and Notification of Environmental Documents |
| 21CFR25.60 | Subpart F – Other Requirements |
Judicious Use of Antibiotics: The use of antibiotics in animals has been an exceptionally controversial and debated issue over the past decade, and aquaculture has received more than its share of attention. Several organizations have developed public documents that discuss the issues surrounding antibiotic use in agriculture and/or provide guidance to animal care and health professionals on the judicious use of antibiotics in animals in general and aquatic animals specifically. The organizations of note are FDA's Center for Veterinary Medicine (CVM), the American Veterinary Medical Association (AVMA), the American Academy of Microbiology (AAM), the National Aquaculture Association (NAA), the United Nation's Food and Agriculture Organization (FAO) and the Institute of Food Technologists (IFT). Click on document number to view actual documents.
Organization/ Document Number |
Title |
| "Antimicrobial Resistance: Implications for the Food System." An Expert Report (July 2006) | |
| "Judicious Use of Antimicrobials of Aquatic Veterinarians" (Jan 2006) | |
| "Responsible Use of Antibiotics in Aquaculture" (2005) | |
| “Judicious Therapeutic Use of Antimicrobials” – an overview of AVMA’s approach to better understanding the issue of antimicrobial resistance | |
| “Judicious Therapeutic Use of Antimicrobials by Veterinarians” – AVMA’s slide presentation | |
| “Judicious and Prudent Antimicrobial Drug Use Principles for Food Fish Veterinarians” – contains AVMA’s principles as they apply to food fish | |
| “Judicious Antimicrobial
Use in US Aquaculture: Principles and Practices” |
|
"The role
of Antibiotics in Agriculture" |
Drugs used in aquaculture: The National Aquaculture Association has also published a document, “Drugs Used in the US Aquaculture Industry,” which is a relatively comprehensive review of drugs used by the domestic aquaculture industry. The stated purpose of the document is to (a) “…identify the drugs federally approved for use in the US aquaculture industry…” (b) “…examine their use limitations…” (c) “… provide estimates of the volume of antibiotics used in the domestic industry…” (d) “…discuss one of the more commonly used chemicals, copper sulfate…” and (e) discuss “…the use of drugs in aquaculture outside the US…” The NAA document can be found on their website at:
http://www.thenaa.net/downloads/Drugs_and_Chemicals_in_US_Aquaculture_11.10.pdf
Drug use in the context of animal care and research: The American Fisheries Society (AFS), in partnership with the American Institute of Fishery Research Biologists and the American Society of Ichthyologists and Herpetologists have published an extensive set of guidelines that are “…intended to provide general recommendations on field and laboratory activities, such as sampling, holding, and handling fishes; information on administrative matters, including regulations and permits; and advice concerning ethical questions, such as perceptions of pain or discomfort that may be experienced by experimental subjects.” The “Guidelines for the Use of Fishes in Research” discuss, among a variety of other topics, anesthetics, drugs, vaccines, hormones and other chemicals used in fish culture. These discussions are provided by the authors in the context of a “…respect for life processes, the forms of life that make up the various ecosystems, and the humane treatment of animals used in research investigation.” These guidelines can be found on the AFS website at:
http://www.fisheries.org/afs/docs/policy_guidelines2004.pdf
Guidance on drug and chemical residue avoidance: The Food Animal Residue Avoidance Database (FARAD) is a National Food Safety Project administered and funded, in the past, through the U.S. Department of Agriculture Cooperative State Research, Education, and Extension Service in cooperation with North Carolina State University, the University of California-Davis and the University of Florida.
FARAD is “…a computer based decision support system designed to provide livestock producers, extension specialists, and veterinarians with practical information on how to avoid drug, pesticide and environmental contaminant residue problems. The drugs and pesticides used in modern animal agriculture improve animal health and thereby promote more efficient and humane production.”
Beginning 15 May 2007 the FARAD database will no longer be publicly accessible online due to lack of Federal funding. It appears that databasei is still available as a CD-ROM. Further information on FARAD can be found at the following website.
Vaccines and other biologics: The Service’s AADAP program has to date not participated in activities relating to the approval of vaccines and other similar products referred to as biologics. This class of products includes vaccines, bacterins, toxoids, antiserums, antitoxins, allergenic extracts, diagnostics, bacterial extracts and combinations of several of the previously mentioned products. The approval and registration of this class of products falls under the jurisdiction of the USDA, Animal and Plant Health Inspection Service’s Center for Veterinary Biologics (CVB) in Ames, Iowa. More information can on Biologics can be found at CVB's website:
http://www.aphis.usda.gov/vs/cvb/
