Regulations
R. A. Libby and F. E. Freeberg The Procter & Gamble Co. Cincinnati, Ohio 45247
Better Regulations: A Case in Point Several recent articles have been written concerning governmental reg ulations that impact directly on the conduct of research. This article will describe the final phase of the regula tory cycle on one such set of regula tions—the FDA's Good Laboratory Practices (GLP) regulations—and how input to the Agency by those sci entists to be regulated importantly af fected the final regulations. The background on the GLP's has been reported in several recent arti cles (1-3). The GLP's were published initially as a proposal in the Federal Register, November 19, 1976. The reg ulations in their final form were pub lished in the Federal Register on De cember 22,1978, and will become ef fective June 20,1979. These regula tions are intended to improve the
quality of animal safety data submit ted to the Agency in support of a re search or marketing permit in the areas of food additives, drugs, and de vices. As proposed initially in 1976, the GLP's were a detailed series of rules that essentially told the scientist how to conduct his research. Left un changed, these regulations would have impeded the science of toxicology both in terms of scientific growth and in in creasing the costs of safety testing. In addition to toxicologists, the GLP's regulate the scientific input from any scientist contributing data to a safety study. One such group is analytical chemists, who analyze the chemical being tested, samples of animal feed or water containing the chemical, and animal body fluids and tissues to de
termine the fate of the chemical in the biological system. The GLP's, when proposed, provid ed a comment period of 120 days to any interested persons to provide input to the Agency. In addition, two public meetings were held by the FDA for the presentation of oral testimony on the proposal. The results were 22 oral presentations and 174 written comments. These comments were sub mitted by manufacturers of regulated products, trade associations, medical centers, private testing or consulting laboratories, educational institutions, other Government agencies, and pri vate individuals. Also, other substan tive comments were made after the formal comment period and provided additional input during the Agency review period. After these comments
Table I. Major Federal Regulatory Agency Proposals Affecting Analytical Chemistry Title
Scientific area
Involvement
Status3
Agency
Good La moratory Practices (GLP)
Toxicological Safety Test material characterization; Studies animal fluid/tissue analysis
FDA
Final regulation in Federal Register 12/22/78, ρ 59986, effective 6/20/79
Good Clinical Practices (GCP)
Human Efficacy/ Safety Studies
Test material characterization; human fluid/tissue analysis
FDA
Proposed in part in Federal Register 9/27/77, ρ 49612; further proposals expected 1979
Bioequi ν alence/Bioavailanility
Biopharmaceuticai Studies
Body fluid/tissue analysis; methods development (Pharmacokinetic)
FDA
Proposal expected 1979
Federal insecticide, Fungicide & Rodenlicide Act < FIFR A )—Registration Guidelines
Environmental/Toxi Test material characterization; cology Efficacy/ residue analysis Studies
EPA (pesti cides)
Proposed in part in Federal Register 7/10/78, ρ 29696. Comments deadline 9/8/78. Final regulations in late 1979
Toxic Substances Control Act (T5CA)—Sect, 4, Testing Standards
Human and Environmental Safety
Method development (trace levels)
EPA (chemi cals)
Proposal early 1979
Cancer Policy (Various Federal Agencies)
Human and Environmental Safety
Regulation of hazardous chemicals. OSHA Affect facility design; exposure to and how, or if, chemicals can be used CPSC
IRLG—Roport: Guidelines for Identifying Carcino gens 3
Human and Environmental Safety
Test material characterization; residue analysis
Proposed final regulations in Federal Register 10/4/77, ρ 54148, possible mid-1979
EPA
Proposed in Federal Register 6/13/78, ρ 25658. Federal court injunction Revised policy possible in 1979
IRLG (reps. from FDA, OSHA, CPSC, EPA)
Report—"Scientific Bases for Identifying Potential Carcinogens and Estimating Their Risks" was released 2/7/79
For information on any regulations proposed in the Federal Register, the federal agencies identified may be contacted for copies of proposals.
0003-2700/79/0351 -579A$01.00/0 © 1979 American Chemical Society
ANALYTICAL CHEMISTRY, VOL. 5 1 , NO. 6, MAY 1979 · 579 A
were received, the FDA evaluated each comment for its merit and how the specific suggested change would meet the Agency's need for ensuring the best possible data. In the pream ble of the final GLP regulations in the December 22,1978, Federal Register, the comments received by the Agency are each discussed with the Commis sioner's reason for accepting or reject ing each suggestion. Many suggestions were accepted. A critical one from the analytical aspect was that the material being safety tested can be "appro priately characterized" rather than identity, strength, quality, and purity being automatically specified. This critical change permits sound scientif ic judgment to be exercised in the characterization of the materials being tested. Because of the Agency, the final GLP's are more manageable, less cost ly, and still.meet the original purpose. Many of the details on exactly how the scientific work is to be conducted have been eliminated, and profession al judgment can replace detailed rules. This final GLP still meets the Agen cy's needs, but does not place an undue burden on the scientists in volved in assessing the safety of new chemicals. The final GLP regulations demonstrate the desire on the part of the Agency to work with those regulat ed to produce meaningful rules. With out this willingness to adopt scientific input, there would have been a manyfold increase in cost of safety testing. More importantly, the number of safe ty tests and the time required to com plete safety work would have de creased the number of new health products made available to the con sumer. The regulatory area continues to change, and there are many similar chances for scientific input to a gov ernmental agency. For example, the Environmental Protection Agency (EPA) will issue in the coming months their version of the GLP's covering safety studies for the materials they regulate. To avoid considerable confu sion, it is imperative that the EPA's rules be consistent with final GLP's from the FDA. Those to be regulated should carefully examine the EPA's proposed GLP rules and provide the EPA with written comments on unac ceptable aspects. Table I lists regula tory proposals or anticipated propos als that should be of interest to ana lytical scientists and deserve their input. References (1) William Horwitz, Anal. Chem., 50 (6), 521A (1978). (2) Robert M. Hodges, ibid., ρ 531Α. (3) R. A. Libby, ibid. (10), 575A (Sept. 1978).
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