Federal Register / Vol. 64, No. 166 / Friday, August 27, 1999 / Rules and Regulations 46841 DEPARTMENT OF HEALTH AND for the prevention of vitamin K additional information supporting HUMAN SERVICES deficiency and as a source of approval of the petitioned use, supplemental niacin when used at a rate specifically the GLP statement as Food and Drug Administration not to exceed 2 grams per ton (g/t) of described in § 571.1(k). FDA believes complete feed. Heterochemical Corp., this course of action is appropriate to 21 CFR Part 573 111 East Hawthorne Ave., Valley supplement the record. FDA will also [Docket No. 94F±0283] Stream, NY 11580, filed objections to clarify the reasons for approving the the final rule in its entirety alleging that FAP, and provide Heterochemical and Food Additives Permitted in the Feed the studies upon which the petition any other interested party with an and Drinking Water of Animals; relies failed to conform to good opportunity to proffer facts that Menadione Nicotinamide Bisulfite laboratory practices (GLP's) or good demonstrate FDA's basis for approving clinical practices (GCP's), and that the FAP 2228 was incorrect. AGENCY: Food and Drug Administration, regulation promotes deception of the FDA is therefore republishing the HHS. consumer and misbranding of the final rule and providing an additional ACTION: Final rule; republication and product. Heterochemical's objections 30 days for submission of objections or opportunity to file objections or are: of additional information in support of additional information. 1. The record of the studies fails to the objections that have already been establish that any of the nonclinical SUMMARY: filed. In accordance with its discretion The Food and Drug laboratory studies (including target Administration (FDA) is republishing, under section 409(f) of the act (21 U.S.C. animal safety) on which the regulation 348(f)), FDA is not staying the final rule. with additional information, a final rule is based were conducted in accordance that published in the Federal Register of FDA will consider a stay, however, if with GLP's as described in part 58 (21 one is requested, after having evaluated January 2, 1996 (61 FR 5). The rule CFR part 58). The record also fails to amended the food additive regulations any objections or other information filed provide, alternatively, a reason for in response to this document. (animal use) to reflect approval of a food noncompliance as required by § 571.1(k) additive petition (FAP) filed by Vanetta (21 CFR 571.1(k)). Furthermore, the II. Administrative Record (U.S.A.) Inc. Objections to the final rule record does not provide a basis for were filed. FDA is not acting on the A. Question of Adherence to GLP's (Part identifying the differences between the 58 and § 571.1(k)) objections in this document, but is practices used and those required by the clarifying the basis of approval of the GLP regulations, so as to permit an In filing an FAP, the petitioner is petition and providing additional evaluation of the studies' integrity and required to provide data and information. The agency also is reliability (i.e., if the target animal safety information to support the safe use of providing a new 30-day period for the studies are flawed, there is no the product as required by section submission of objections or of information in support of the safety of 409(c)(1) of the act. The supporting data additional information in support of the the food additive) (Ref. 1). and information include full reports of objections that were previously filed. 2. The record of the studies fails to investigations made with respect to the FDA has not stayed the effective date of establish that any of the clinical studies safety of use of the additive, including the final rule, effective January 2, 1996. on which the regulation is based were information as to the methods and DATES: Objections, additional conducted in accordance with GCP's as controls used in conducting the information in support of the previously illustrated in FDA's Center for investigations. Part 58 prescribes GLP's filed objections, or additional written Veterinary Medicine's (CVM's) guidance for conducting those nonclinical objections and requests for a hearing, document entitled ``Guideline on the laboratory studies that are used to must be submitted by September 27, Conduct of Clinical Investigations: support or are intended for use to 1999. Responsibility of Clinical Investigators support FAP's or marketing permits for ADDRESSES: Submit written objections and Monitors for Investigational New products regulated by FDA. Compliance and/or additional information in Animal Drug Studies,'' October 1992 with GLP's is intended to ensure the support of objections previously (the guidelines cited by the objection quality and integrity of the safety data submitted to the Dockets Management were supplanted by a revised document filed to support approval of an FAP. If Branch (HFA±305), Food and Drug in May 1997) (Ref. 2). nonclinical laboratory studies are Administration, 5630 Fishers Lane, rm. 3. Heterochemical objects to the involved, an FAP shall include, for each 1061, Rockville, MD 20852. regulation in that it establishes MNB as study, a statement that the study was FOR FURTHER INFORMATION CONTACT: a source of supplemental niacin and conducted in compliance with GLP Sharon A. Benz, Center for Veterinary authorizes labeling the product as a requirements set forth under part 58, or Medicine (HFV±228), Food and Drug source of supplemental niacin. Based on if the study was not conducted in Administration, 7500 Standish Pl., a low level of niacin supplementation, compliance with the GLP's, a brief Rockville, MD 20855, 301±827±6656. the firm contends that the labeling statement with the reason for SUPPLEMENTARY INFORMATION: promotes deception of the consumer noncompliance. and results in misbranding of food In FAP 2228, Vanetta submitted a I. Background within the meaning of the Federal Food, journal article (Ref. 1) supporting In the Federal Register of January 2, Drug, and Cosmetic Act (the act). approval of its petition. The studies 1996, FDA published a final rule that The preamble of the January 2, 1996, reported in the article were not amended the food additive regulations final rule stated that FDA evaluated the conducted in accordance with GLP's, (animal use) to reflect approval of an data presented in the petition and and Vanetta did not submit a statement FAP (FAP 2228) filed by Vanetta concluded that use of the product is of the reason for noncompliance. (U.S.A.) Inc., 1770 East Market St., York, safe. The final rule stated that the food Accordingly, FDA is reopening the PA 17402. The final rule provides for additive regulations would be amended administrative record to include a the safe use of menadione nicotinamide as requested in the FAP. FDA is now statement from Vanetta on the reasons bisulfite (MNB) as a nutritional republishing the final rule to clarify its for the studies' noncompliance with supplement in chicken and turkey feeds basis for approval, and to provide GLP's, as required under § 571.1(k). VerDate 18-JUN-99 08:52 Aug 26, 1999 Jkt 183247 PO 00000 Frm 00027 Fmt 4700 Sfmt 4700 E:\FR\FM\A27AU0.076 pfrm04 PsN: 27AUR1 46842 Federal Register / Vol. 64, No. 166 / Friday, August 27, 1999 / Rules and Regulations B. Clarification of the Record demonstrating that inclusion of MNB in The approved conditions of use, as The objections Heterochemical filed chick diets improved blood clotting specified in the MNB regulation (21 CFR in response to FDA's approval of MNB when compared to negative controls. 573.625(b)), state that MNB can be used point out that the basis for the agency's The improvements observed in the as a ``nutritional supplement in chicken decision was not clear. The study were similar to those seen when and turkey feeds for both the prevention administrative record for FAP 2228 another accepted source of vitamin K of vitamin K deficiency and as a source included various agency comments on activity was added to experimental of supplemental niacin.'' The conditions of use appropriately the studies reported in the journal diets. The highest level of menadione compare the levels of vitamin K activity article by Oduho et al. The objector utilized in this study, 0.4 milligram from menadione and nicotinamide by interpreted the comments to mean that (mg)/kg diet, approaches that stating that MNB can prevent a vitamin the studies were invalid and thus did recommended by the National Research K deficiency, but is simply a source of not support approval of the FAP. Council, 0.5 mg/kg, for the type of birds niacin. As noted previously, niacin can Contrary to the objector's interpretation, used in this experiment (Ref. 7). The serve as a generic name for all pyridine- the agency's comments on the Oduho adequacy of 0.4 mg to meet the birds' 3-carboxylic acids that exhibit studies did not question their validity, nutritional requirement is demonstrated nicotinamide activity (Ref. 3). By using and do not invalidate the agency's final by the fact that the prothrombin times the different terms, the conditions of use decision that MNB is safe and achieves of 17 and 19 seconds for MNB and establish that MNB provides different its intended technical effect. However, menadione dimethylpyrimidinol levels of vitamin K and niacin activities. the objections made it clear that the bisulfite (MPB), an accepted source of The directions for use on the product agency needed to make additional vitamin K activity (21 CFR 573.620), fall label specify the minimum amount of comments to clarify the record.