Regulations
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More Good Laboratory Practices On June 20, 1979, the Food and Drug Administration's (FDA) final Good Laboratory Practice (GLP) reg ulations became effective. These rules culminate a multiyear effort by the FDA which has had far-reaching ef fects on the conduct of nonclinical safety (animal toxicological) testing. These rules set standards on how to conduct laboratory testing and in cluded analytical work done to charac terize the chemical being tested. A re view of the GLP's has been the subject of several JOURNAL articles (1-3). The far-reaching nature of the FDA GLP's is reflected in the widespread adoption of the GLP concept by other government regulatory agencies. The Environmental Protection Agency (EPA) recently proposed (Feci. Regist., 44, 27362, May 9, 1979) Good Laboratory Practice standards for long-term nonclincal testing for chem icals falling under Section 4 of Toxic Substances Control Act regulations. Also, another branch of the EPA, the Office of Pesticide Programs, will be proposing additional GLP sections as part of guidelines for nonclinical test ing of all pesticides. Further, the GLP's are taking an international fla vor, as the Organization for Economic Cooperation and Development (OECD) is in the process of devel oping "Principles of Good Laboratory Practices" to be used on a multina tional basis for the generation of non clinical laboratory data. While these GLP rules are being written for the science of toxicology, they also'impact on many other disci plines, including analytical chemistry (/). This results because the analytical chemist provides methods and data on characterization and stability of the chemical to be tested; level, homo geneity, and stability of the chemical in the feed mixture; analysis of the diet mixture for possible contami nants; and the analysis of tissue and body fluid for test compound or me tabolites. While the GLP's as published by the FDA have provided some benefit by stimulating improvement in the
operation of toxicological testing facil ities, added GLP proposals by other regulators raise the spectre of multiple regulatory bodies publishing differing regulations on the same subject. Since many of the materials and most of the laboratories to which the FDA GLP's will apply are also subject to regula tions of many agencies, it is important that these laboratory rules from vari ous agencies precisely coincide with one another. Differing regulations could substantially increase the chance of unintentional errors as labo ratories attempt to cope with differing rules. In addition, safety tests to be submitted to several agencies might have to be rerun simply because of the differing logistical rules of each agen cy. This would result in heedless waste of scarce scientific resources and in crease costs unnecessarily. The newly proposed EPA GLP's are a serious concern in this area of con sistency. It is true that they propose general GLP's which are similar to those of the FDA. But, in addition to their general GLP's, the EPA has also proposed many more GLP require ments as part of the test standards for the conduct of specific animal tests. Many of these specific rules differ from the GLP rules of the FDA and the EPA's general GLP's. An example of these differences important to ana lytical chemists is specification that the level of test substance in diets not vary more than ±5%. This latter re quirement could be impossible to achieve analytically for diets contain ing ppm levels of the chemical being tested. Ironically, in most cases it may not be scientifically necessary to achieve this degree of accuracy be cause of inherent variability with other aspects of biological testing. A second requirement that will re quire considerable analytical effort is the analysis of animal feed for 44 nu trients and 14 contaminants to rela tively tight specifications. Finally, as an unusual addition to the generic chronic testing protocol, analyses of test compounds or their metabolites in tissue residues and body fluids are
CIRCLE 192 ON READER SERVICE CARD 1206 A • ANALYTICAL CHEMISTRY, VOL. 5 1 , NO. 12, OCTOBER 1979
0003-2700/79/A351-1206$01.00/0 © 1979 American Chemical Society
MAJOR FEDERAL REGULATORY AGENCY PROPOSALS AFFECTING ANALYTICAL CHEMISTRY Title
Primary Analytical Involvement
Scientific Area
Good Clinical Practices (GCP)
Human Efficacy/Safety Studies
Bioequivalence/ Bioavailability
Biopharmaceutical Studies Body fluids/tissues analysis; methods development (Pharmacokinetic)
Test material characterization; human fluid/ tissue analysis
Agency
Status*
FDA (Drugs)
Proposed in part in Federal Register 9/27/ 77; p. 49612, further proposals expected 1980.
FDA (Drugs)
Proposal expected 1979.
Federal Insecticide, Environmental/Toxicology Test material Fungicide & Rodenticide Efficacy/Studies characterization; Act (FIFRA)— residue analysis Registration Guidelines
EPA (Pesticides)
Proposed in part in Federal Register 7/10/ 78; p. 29696. Comments deadline 9/8/ 78. Comments deadline reopened.
Toxic Substances Control Human and Environmental Method development Act (TSCA)—Sect. 4, Safety (trace levels) Chronic Testing Standards and GLP's
EPA (Chemicals)
Proposed in Federal Register 5/9/79; comments deadline (extended to) 10/ 16/79.
Toxic Substances Control Human and Environmental Method development Act (TSCA)—Sect. 4, Safety (trace levels) Acute & Subchronic Toxicity, Mutagenic & Teratogenic Effects, & Metabolism Studies
EPA (Chemicals)
Proposed in Federal Register 7/26/79; comments deadline 10/16/79.
Cancer Policy Human and Environmental Regulation of hazardous chemicals. (Various Federal Agencies) Safety Affect facility, design, exposure to and how, or if,
OSHA
Proposed final regulations in Federal Register 10/4/77; p. 54148. Final regs. expected second half 1979. Proposed 6/13/78; p. 25658. Federal court injunction; Policy subsequently withdrawn. Revised policy possible in 1979. Laboratory Guidelines proposed in Federal Register 6/14/79; comments deadline 8/14/79.
CPSC
chemicals can be used. EPA HEW
IRLG—Report: Guidelines Human and Environmental Test material for Identifying Safety characterization; Carcinogens and residue analysis Estimation of Risks
Chemical Compounds in Food-Producing Animals—Carcinogenic Residues
Human and Environmental Analytical methods Safety development
IRLG IRLG's report released earlier (2/7/79) was (Reps, from FDA, officially published in Federal Register OSHA, CPSC, 7/6/79, comments deadline 9/30/79. EPA) FDA
Proposed in Federal Register 3/20/79; comments deadline (extended to) 9/4/79.
* For information on any regulations proposed in the Federal Register, the federal agencies identified may be contacted for copies of proposals.
required. This is particularly troublesome since this will require the analytical chemist to develop methods to measure the test material and its metabolites in complex biological systems at ppm or lower levels. This will likely result in more than doubling the cost of the chronic test. T h e widespread adoption of G L P principles will not end with standards for development of toxicological testing data. It is apparent t h a t the modern scientist must plan for the inclusion of governmental rules covering those aspects of this work t h a t will be reviewed by interested regulatory agencies. Evidence for this conclusion is contained in the Preamble for the EPA's recent G L P proposal (Fed. Regist., 44, 27368, May 9, 1979) where
the agency states t h a t it is "currently drafting G L P standards for the conduct of studies for ecological effects and chemical fate testing." T h e analytical chemist plays a considerable technical role in these types of testing, and any G L P ' s developed will apply to analytical operations. In this same Preamble, the E P A confirms t h a t it expects all data generated in countries outside the United States to conform to these same rules. In order to ensure this, the E P A is working with the international groups to develop worldwide Good Laboratory Practices standards. T h u s , analysts all over the world will eventually be affected. Analytical scientists must be willing to interact with any regulatory agency developing logistical rules affecting
their science to ensure consistent, effective, and sensible regulations. These comments should be aimed at improving the regulations from the standpoint of practicability without increasing the risk of producing poor results. T h e table is an update of the most recent (and expected) regulatory activity affecting the analytical chemist. Some of the more important of these regulations will be discussed in future issues.
References (1) R. A. Libby, Anal. Chem., 50, 575A (1978). (2) William Horwitz, Anal. Chem., 50, 521A (1978). (3) Robert M. Hodges, Anal. Chem., 50, 531A (1978).
ANALYTICAL CHEMISTRY, VOL. 51, NO. 12, OCTOBER 1979 • 1207 A
