Federal Register/Vol. 63, No. 239/Monday, December 14, 1998

Federal Register / Vol. 63, No. 239 / Monday, December 14, 1998 / Notices 68775 issued export certificates. The new facilitate the issuance and tracking of Drug Administration Modernization Act format may also help authenticate export certificates, deter unscrupulous of 1997 (FDAMA). export certificates. persons from making counterfeit or false DATES: Submit data and information by DATES: The agency will begin issuing certificates or otherwise tampering with March 15, 1999. Submit written general export certificates using the new format export certificates, and to help foreign comments by March 15, 1999. after January 1, 1999. governments identify authentic, FDA- ADDRESSES: Submit written general FOR FURTHER INFORMATION CONTACT: issued export certificates more readily, comments on this call-for-data to the Philip L. Chao, Office of Policy (HF–23), FDA has adopted a new format for its Dockets Management Branch (HFA– Food and Drug Administration, 5600 export certificates. The new format 305), Food and Drug Administration, Fishers Lane, Rockville, MD 20857, features the use of several security 5630 Fishers Lane, rm. 1061, Rockville, 301–827–3380. measures in the paper used for export MD 20852. Submit information on certificates. human drug products to the Division of SUPPLEMENTARY INFORMATION: Firms FDA will begin using the new format Over-the-Counter (OTC) Drug Products exporting products from the United on certificates issued after January 1, (HFD–560), Center for Drug Evaluation States are often asked by foreign 1999. The procedures for requesting and and Research, Food and Drug customers or foreign governments to issuing export certificates, as well as the Administration, 5600 Fishers Lane, supply a certification relating to text of the certificates themselves, will Rockville, MD 20857. Submit products subject to the Federal Food, remain unchanged. Drug, and Cosmetic Act (the act) and However, FDA will not use the new information on veterinary drug products other FDA-administered acts. format on European Union (EU) Export to the Division of Epidemiology and Certification is the process by which a Health Certificates. These certificates Surveillance (HFV–210), Center for formal or official attestation is made are for fishery products intended for Veterinary Medicine, Food and Drug concerning a product’s regulatory status import into the EU and are not Administration, 5600 Fishers Lane, or the system by which a commodity is considered to be FDA certificates. Rockville, MD 20857. Submit manufactured. Certification does not FDA is notifying foreign embassies information on food products, including show that FDA has ‘‘approved’’ the and its counterpart government agencies dietary supplements, to the Office of product for export; however, some of the new format and also advising Special Nutritionals (HFS–456), Center certificates reflect that the product has them that otherwise valid export for Food Safety and Applied Nutrition, been approved for marketing in the certificates issued before January 1, Food and Drug Administration, 200 C United States. 1999, remain valid. Consequently, St. SW., Washington, DC 20204. FDA currently issues several types of persons whose export certificates were FOR FURTHER INFORMATION CONTACT: certificates. In brief, the principal issued before January 1, 1999, but expire For human drug products: Gerald M. certificates are: after that date, should not need to Rachanow, Center for Drug 1. Certificates to Foreign replace those certificates. Evaluation and Research (HFD– Government—used for products that 560), Food and Drug Dated: December 4, 1998. may be legally marketed, sold, offered Administration, 5600 Fishers Lane, for sale, or distributed in the United William K. Hubbard, Rockville, MD 20857, 301–827– States. For food products, these are Associate Commissioner for Policy 2222. commonly known as ‘‘certificates of free Coordination. For veterinary drug products: William sale’’ or ‘‘certificates of export.’’ [FR Doc. 98–33052 Filed 12–11–98; 8:45 am] C. Keller, Center for Veterinary 2. Certificates of Exportability—used BILLING CODE 4160±01±F Medicine (HFV–210), Food and for products that meet the requirements Drug Administration, 5600 Fishers for export under section 801(e) or 802 of Lane, Rockville, MD 20857, 301– the act (21 U.S.C. 381(e) or 382)) but DEPARTMENT OF HEALTH AND 827–6641. may not otherwise be marketed, sold, HUMAN SERVICES For food and dietary supplement offered for sale, or distributed in the Food and Drug Administration products: Sharon A. Ross, Center United States. for Food Safety and Applied 3. Certificates of a Pharmaceutical [Docket No. 98N±1109] Nutrition (HFS–456), Food and Product—used for pharmaceutical Drug Administration, 200 C St. SW., products and conform to the format in Mercury Compounds in Drugs and Washington, DC 20204, 202–205– the World Health Organization’s Food; Request for Data and 5343. Information ‘‘Certification Scheme on the Quality of SUPPLEMENTARY INFORMATION: Pharmaceutical Products Moving in AGENCY: Food and Drug Administration, I. Background International Commerce.’’ HHS. FDA’s Center for Biologics Evaluation ACTION: Notice; request for data and FDAMA (Pub. L. 105–115) was and Research, Center for Drug information. enacted on November 21, 1997. Section Evaluation and Research, Center for 413 of FDAMA, entitled ‘‘Food and Devices and Radiological Health, Center SUMMARY: The Food and Drug Drug Administration Study of Mercury for Food Safety and Applied Nutrition, Administration (FDA) is announcing a Compounds in Drugs and Food,’’ and Center for Veterinary Medicine call-for-data to identify food and drug requires FDA to: (1) Compile a list of receive and process requests for export products that contain intentionally drugs and foods that contain certificates for products subject to their introduced mercury compounds, e.g., intentionally introduced mercury respective authorities. mercurous chloride, mercuric chloride, compounds, and (2) provide a Recently, there has been an increasing phenylmercuric acetate, thimerosal. The quantitative and qualitative analysis of demand for export certificates, as well agency is seeking both quantitative and the mercury compounds in this list. as requests from foreign governments to qualitative information about the FDAMA requires the agency to compile authenticate certificates and instances mercury compounds in these food and the list and provide the analysis within where FDA has found counterfeit or drug products. This request is part of 2 years after the date of its enactment. falsified certificates. Consequently, to the implementation of the Food and The statute does not differentiate 68776 Federal Register / Vol. 63, No. 239 / Monday, December 14, 1998 / Notices whether the mercury compound is used in human drug products. Inorganic FDA has already evaluated the safety present in the products as an active or mercury salts used include mercurous and effectiveness of many of the OTC an inactive ingredient. Therefore, FDA chloride (calomel) and mercuric uses of mercury compounds as part of is requesting data and information on chloride (bichloride of mercury). its OTC drug review. Many mercury any mercury compounds, present as Organic aryl mercury compounds used compounds used as active ingredients active or as inactive ingredients, in any include phenylmercuric acetate and in OTC drug products have been found human or veterinary drug (prescription phenylmercuric nitrate. Some of these to be not generally recognized as safe or OTC) product or any food product, mercury compounds (e.g., (GRAS) and effective and are classified including dietary supplements. phenylmercuric acetate and as new drugs. These mercury phenylmercuric nitrate) have been used II. Mercury Compounds in Human Drug ingredients are listed in § 310.545(a) (21 as both active and inactive ingredients. Products CFR 310.545(a)) (see Table 1 of this Some mercury-containing drug products document). There are several different types of have been marketed by prescription and mercury compounds that have been others have been marketed OTC only.

TABLE 1.ÐMERCURY INGREDIENTS LISTED IN 21 CFR 310.545(a)

Rulemaking and Ingredients Paragraph

Dandruff/seborrheic dermatitis/psoriasis drug products (Docket No. 82N±0214) 310.545(a)(7) Mercury oleate External analgesic drug products: Poison ivy/poison oak/poison sumac drug products (Docket No. 78N± 310.545(a)(10)(vii) 301P) Merbromin (mercurochrome) Mercuric chloride (bichloride of mercury, mercury chloride) Laxative drug products: Stimulant laxatives (Docket No. 78N±036L) 310.545(a)(12)(iv) Calomel (mercurous chloride) Skin bleaching drug products (Docket No. 78N±0065) 310.545(a)(17) Mercury, ammoniated Skin protectant drug products: Poison ivy/poison oak/poison sumac drug products (Docket No. 78N±021P) 310.545(a)(18)(vi) Merbromin (mercurochrome) Mercuric chloride (bichloride of mercury, mercury chloride) Ophthalmic drug products: Anti-infective (Docket No. 80N±0145) 310.545(a)(21)(ii) Mercuric oxide, yellow First aid antiseptic drug products (Docket No. 75N±183F) 310.545(a)(27)(i) Ammoniated mercury Calomel (mercurous chloride) Merbromin (mercurochrome) Mercufenol chloride (ortho-chloromercuriphenol, ortho-hydroxyphenylmercuric chloride) Mercuric chloride (bichloride of mercury, mercury chloride) Mercuric oxide, yellow Mercuric salicylate Mercuric sulfide, red Mercury Mercury oleate Mercury sulfide Nitromersol Para-chloromercuriphenol Phenylmercuric nitrate Thimerosal Vitromersol Zyloxin Antimicrobial diaper rash drug products (Docket No. 75N±183D) 310.545(a)(27)(ii) Para-chloromercuriphenol Any other ingredient containing mercury Vaginal contraceptive drug products (Docket No. 80N±0280) 310.545(a)(28) Phenylmercuric acetate Phenylmercuric nitrate Any other ingredient containing mercury

FDA has also considered mercury ‘‘mercury’’ or ‘‘(insert name of mercury- other homeopathic drug products. compounds as inactive ingredients in containing ingredient) or any other Therefore, homeopathic drug products OTC ophthalmic drug products. Section ingredient containing mercury).’’ are included in this call-for-data. 349.50(c)(3) of the final monograph for The agency is aware that mercury OTC ophthalmic drug products (21 CFR III. Mercury Compounds in Veterinary compounds (e.g., phenylmercuric Drug Products 349.50(c)(3)) states: acetate and thimerosal) are used as a For ophthalmic drug products containing preservative in OTC nasal solution Currently, there are no approved mercury compounds used as a preservative. ‘‘This product contains (name and quantity products and prescription ophthalmic veterinary drug products that contain a of mercury-containing ingredient) as a drug products. Phenylmercuric nitrate is mercury compound as an active preservative. Do not use this product if you also present in some oral homeopathic ingredient. There is some limited use, are sensitive to’’ (select one of the following: drug products and may be present in Federal Register / Vol. 63, No. 239 / Monday, December 14, 1998 / Notices 68777 veterinary drug products. These examined, listed cinnabar as an ingredient, state the pharmacologic products are all unapproved OTC ingredient on the label (Ref. 2). In this use(s) of the product. If an inactive products for use in nonfood species. For study, 35 of 251 products that were ingredient, state the function (e.g., instance, older text books may contain screened for mercury content were preservative); an indication for red mercuric iodide found to contain significant quantities 5. Provide a copy of the product’s petrolatum as a compounded of mercury (Refs. 2 and 3). Additionally, labeling; and counterirritant. An aqueous formulation the study showed that most of the 6. Estimate the amount of the mercury of red mercuric iodide is commercially products that contained significant compound used annually in marketed with that indication. quantities of mercury did not list manufacturing the product. Mercurochrome is currently marketed mercury sources on the label. Therefore, for treating bacterial diseases of it is not possible to determine whether VII. Request for Data and Information ornamental fish. The potential exists for the mercury in these products is Affected manufacturers should, on or some limited use of mercury intentionally added or is present as an before March 15, 1999, submit the data compounds as inactive ingredients, unintended ingredient or contaminant. and information requested in section VI such as preservatives, particularly in Other than this limited information, of this document. Two copies of the unapproved products. FDA is not aware of other uses of data and information are to be IV. Mercury Compounds in Food mercury in dietary supplements. submitted, except that individuals may Products V. References submit one copy. Data and information should be addressed to the appropriate The agency has limited information The following references have been FDA centers (Drug Evaluation and on the intentional addition of mercury- placed on display in the Dockets Research, Veterinary Medicine, or Food containing compounds to food products. Management Branch (address above) Safety and Applied Nutrition) Under section 201(s) of the Federal and may be seen by interested persons (addresses above). All submitted data Food, Drug, and Cosmetic Act (the act) between 9 a.m. and 4 p.m., Monday and information on the quantitative (21 U.S.C. 321(s)), an ingredient used in through Friday. food or as food must be an approved amount of the mercury compound 1. Bensky, D., A. Gamble, and T. Kaptchuk, present in the product (unless the food additive or it must be GRAS for its Chinese Herbal Medicine Materia Medica, intended food use. Currently, FDA has 8th Ed., Eastland Press, Inc., Seattle, pp. 573– information appears in product labeling) not approved any mercury-containing 574, 638–639, 1992. and the amount of the mercury compounds as food additives and does 2. Ko, R. J., and A. Au, 1997–1998 compound used annually in not consider any mercury-containing Compendium of Asian Patent Medicines, manufacturing the product will be compounds to be GRAS. California Department of Health Services, handled as confidential by the agency Substances that are ‘‘dietary Food and Drug Branch, Sacramento, 1998. under 21 CFR 20.61. General comments 3. Ko, R. J., ‘‘Adulterants in Asian Patent ingredients’’ as defined in section on this call-for-data should be addressed Medicines,’’ New England Journal of to the Dockets Management Branch 201(ff) of the act are exempt from the Medicine, 339:847, 1998. food additive provisions of the act (address above). General comments are under section 201(s)(6). Under the act, VI. Call-for-Data and Information to be identified with the docket number dietary supplement ingredients subject In order to prepare the list and found in brackets in the heading of this to section 201(ff) do not require FDA provide the analysis required by section document. Received general comments premarket scrutiny or approval. 413 of FDAMA, the agency is requesting may be seen in the Dockets Management Additionally, ingredients subject to this all manufacturers of any food, including Branch between 9 a.m. and 4 p.m., section of the act do not need to be dietary supplement, and human or Monday through Friday. registered with FDA. Consequently, veterinary drug product (prescription or Dated: December 7, 1998. FDA has no listing of mercury- OTC) containing any intentionally William K. Hubbard, containing compounds that are used as introduced mercury compounds, Associate Commissioner for Policy dietary ingredients in dietary whether used as an active or inactive Coordination. supplements. ingredient, to provide FDA the The agency is aware that some [FR Doc. 98–33053 Filed 12–11–98; 8:45 am] following information for each product: BILLING CODE 4160±01±F categories of products marketed as 1. The commercial name of the dietary supplements in the United product that contains the mercury States may contain a source of added compound; DEPARTMENT OF HEALTH AND mercury. Products similar to those that 2. The chemical name (USAN or HUMAN SERVICES are used as traditional medicines in established name, if one exists) of the other countries may sometimes be mercury compound(s) present in the Food and Drug Administration marketed as dietary supplements in the drug product; the Chemical Abstract United States. For example, mercury- Service (CAS) registry (Reg.) number [Docket No. 98F±1122] containing compounds are used in (No.) and the CAS preferred chemical traditional Chinese medicines. The name of the mercury compound(s) GEO Specialty Chemicals; Filing of Chinese Herbal Materia Medica (Ref. 1) present in the food or dietary Food Additive Petition reports that cinnabar (mercuric sulfide; supplement product; cinnabaris or zhu sha in Mandarin 3. The quantitative amount of the AGENCY: Food and Drug Administration, Chinese) and calomel (mercurous mercury compound present in the HHS. chloride; calomelas or qing fen in product. State as either quantity per ACTION: Notice. Mandarin Chinese) have been widely dosage unit or per quantity of product used as a sedative and detoxicant and to (e.g., ounce or gram). State whether SUMMARY: The Food and Drug treat constipation and edema, amount is calculated on a weight to Administration (FDA) is announcing respectively. The California Department weight (w/w) or weight to volume (w/ that GEO Specialty Chemicals has filed of Health Services reported that 5 of 260 v) basis, where applicable; a petition proposing that the food traditional Chinese medicines available 4. State the purpose of the mercury additive regulations be amended to in the retail marketplace, which they compound in the product. If an active provide for the safe use of