The Use of Drugs in Food Animals Benefits and Risks (1999) / Chapter Skim
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4 Drug Development, Government Approval, and the Regulatory Process
4 Drug Development, Government Approval, and the Regulatory Process
Pages 88-109
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From page 88... ...
, the Center for Veterinary Medicine (CVM, within FDA) , the Food Safety and Inspection Service (within USDA)
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From page 89... ...
CVM has the important tasks of protecting society from harmful animal drugs and maintaining public confidence in the drugs that are in use. These objectives are achieved by ensuring that new drugs pass a rigorous approval process.
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From page 90... ...
The INAD is critical because it permits unapproved drugs to be transported to sites where they can be used legally in animal evaluation studies and contains the information needed to obtain an investigation withdrawal time and permission to slaughter test animals. FDA is notified when the animals are slaughtered, and the animals must be slaughtered at a federally inspected facility.
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From page 91... ...
CVM is developing new strategies to be more responsive to sponsors' schedules within the approval process by allowing sponsors to establish the nature of the communications and review process through which approval is sought. For example, initial discussions between CVM and the sponsor will establish early in the development and approval process the expectations for data submission (phased review of data and studies at critical development points versus review of the total data package)
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From page 92... ...
The most recent contributions to streamlining are in the areas of drug availability and "extra-label usage," which allows veterinarians to exercise their judgment to recommend uses for drugs beyond those specified on labels or package insert. A comparison of the old and new approval processes, including schedules, is presented in Figure 4–2.
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From page 93... ...
The adoption of the revised policies was phased in beginning 1993 and 50 360 40 270 30 Months Days 180 20 90 10 0 0 '91 '92 '93 '94 '95 Re-engineered Goal Fiscal Years FIGURE 4–3 Effect of Re-Engineering the Approval Process on the Time to Approve New Animal Drug Applications. Source: CVM Summary of NADA Approvals, 1996.
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From page 94... ...
CVM considers the compassionate INAD a sound measure for offsetting the shortage of approved drugs in aquaculture and in its recommendations for these uses weigh the potential for excessive use against the safety of the intended use. Important new changes in many aspects of the approval process are aimed at clarifying the expectations of submitting and approving parties alike.
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From page 95... ...
For example, the argument can be made that concern for the consequences of antibiotic use in animals on human health is valid even though few data address that concern. In reviewing the issues presented in commissioned papers and invited workshop presentations, the committee identified 6 points for which control over animal drug approval might be too stringent: • FDA technical and regulatory requirements for manufacturing animal drugs are nearly identical to those for human drugs.
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From page 96... ...
The food safety requirements include extensive toxicological testing to calculate acceptable daily intake of residues of the drug. Then, elaborate metabolism and withdrawal studies are required to determine withdrawal times.
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From page 97... ...
Extra-label use did not extend to medicated feeds and, because of human food safety concerns, some drugs were not allowed to be used in food animals under any circumstances. These include diethylstilbestrol (DES)
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From page 98... ...
One asset to AMDUCA is the Food Animal Residual Avoidance Databank (FARAD) , a nationally sponsored project of USDA's Cooperative State Research, Education and Extension Service funded through the Food Safety and Quality national initiative.
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From page 99... ...
However, if the issue of animal drug availability is not addressed aggressively, the legal extra-label drug use actually could be a deterrent to the animal drug industry in its attempts to discover and develop new pharmaceutical products. The Animal Drug Availability Act Given current drug efficacy requirements, relatively few food-animal species and a small number of diseases or production improvement uses are seen by the animal health industry to warrant the risk and capital investment now required for successful drug development.
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From page 100... ...
, signed by President Clinton in October 1996, which introduced many new ways for the regulatory process to approve animal drugs and medicated feeds more rapidly. ADAA's overall intent is to lessen the burden placed on the animal health industry to follow the approval process while maintaining the protection of the public, summarized as follows: • ADAA eliminates the strict requirement for field studies (except as requested and justified by CVM)
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From page 101... ...
Finally, as seen in Table 4–3, 87 percent of all animal drugs have annual individual product sales of less than $1 million, and only 5 percent of the available compounds generate sales of more than $5 million. Animal pharmaceutical companies and animal health divisions of large parent corporations are expected to be financially independent and profitable.
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From page 102... ...
2The Delaney Clause, which was included in the 1958 Food Additives Amendment to the FDCA, directs that "no additive shall be deemed to be safe if it is found to induce cancer when ingested by man or animal, or if it is found, after tests which are appropriate for the evaluation of the safety of food additives, to induce cancer in man or animal."
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From page 103... ...
The redundancy in expected paperwork to substantiate an application submission for government approval and the response time on the part of the authorizing federal agencies were considered by the animal industry to be major impediments to the process and progress of drug development. Historically, the authorizing federal agencies have held firm that the health of the human and animal populations was of paramount importance in the approval process and that the integrity of the process would not be violated.
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From page 104... ...
If a product is approved outside of the United States in a country with a comparable approval process, the process in the United States could be expedited. The areas of human food safety, target-animal efficacy and safety, and environmental fate and worker safety are the major areas of data required in all countries for approval of a veterinary compound.
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From page 105... ...
The United States and the EEC have similar requirements for animal drug approval in all of the major data areas, and decisions regarding ADI revolve around a "no observable effect" definition. Japan differs in its approach to evaluating the human food safety aspects of an animal drug.
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From page 106... ...
, which evaluates human food safety data on selected animal drugs for the Codex Committee on Residues of Veterinary Drugs in Foods (CC/RVDF)
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From page 107... ...
The high cost of new drugs makes them impractical for widespread use in agriculture, especially when a potential use is for disease prevention at subtherapeutic concentrations. In addition, in the past, approval of animal drugs in the regulatory process had the added burden of needing to show human food safety as well, thus adding costly and time-consuming projection studies to the food-animal drug development process.
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From page 108... ...
• More realistic estimates of human dietary exposure should be made when residue tolerance levels are developed. The requirements for human food safety testing for drug-related residues in meat, milk, and eggs are complex, and demanding toxicological tests of the parent drug and any potentially toxic metabolites, residue identification and quantitation, and method development for quantification of residues in edible animal products are required.
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From page 109... ...
Initiating the process of harmonization reform could prove slow and cumbersome, but diligence in this effort should produce a more efficient and responsive collective review and monitoring process. Desirable advances in the regulatory process would be to establish drug use guidelines based on maximum safe regimens for the target food animals, to set drug withdrawal times accordingly, and to develop tests for use on farms to certify the absence of violative residues of toxicologically active drugs or their metabolites.
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