Food, Drug & Devices – July 2010

Topic of the Month:  In July the FDA began to address the issue of food labeling with the creation of a docket for restaurants involved in the process of establishing nutrition content on menus for consumers. The agency noted that in subsequent months it would collect information on the nutrition effort in order to promulgate regulations to enforce provisions as enacted by the Patient Protection and Affordable Care Act of 2010, (PPACA) (PubLNo 111-158) on March 23, 2010.  Various food documents are expected to be issued over the next few months.

I. Agency Developments


Tobacco retailer training program draft guidance issued

A draft guidance for tobacco retailers who wish to implement effective training programs for employees was issued by the FDA. Titled “Tobacco Retailer Training Programs, “the draft guidance outlines training programs and standards to provide for reduced civil money penalties issued under 21 CFR §387(f) as amended by the Family Smoking Prevention and Tobacco Control Act (P.L 111-31, ¶2006). Currently a two schedule penalty program exists, and under each schedule, retailers who violate the new provisions are subject to increasing penalties for multiple violations within prescribed time periods. For the first three violations in a 24-month period, retailers with an approved training program are subject to lower penalties than retailers with no training program. The provisions are designed to limit youth access to cigarettes and smokeless tobacco products, as well as restricting advertising and promotion of such products, to curb the appeal of these products to minors. The draft guidance is to be used until the FDA establishes standards for approved retailer training programs. Until the regulations are issued, all retailers will be penalized for violations under the lower schedule, but retailers who have implemented a program would be subject to reduced penalties.

The draft guidance outlines elements that should be covered in an employee training program including: (1) federal laws restricting the access to, and the advertising and promotion of, cigarettes and smokeless tobacco products; (2) the health and economic effects of tobacco use, especially when the tobacco use begins at a young age; (3) written company policies against sales to minors; (4) identification of the tobacco products sold in the retail establishment that are subject to the Federal laws prohibiting their sale to persons under the age of 18; and (5) age verification methods.

The draft guidance also recommends that retailers implement certain hiring and management practices as part of an effective retailer training program, namely that applicants and current employees be notified both verbally and in writing of the importance of complying with laws prohibiting the sales of tobacco products to persons under the age of 18. Retailers are further advised to implement an internal compliance check program and document the procedures and corrective actions for the program. FDA Notice, ¶42,039

II. Drug and Biologics Developments


Lupus treatment and drug development guidances published

Two guidances providing recommendations for industry on developing human drugs, therapeutic biological products, and medical devices for the treatment of systemic lupus erythematosus (SLE), including lupus nephritis (LN) outcomes, were published by the FDA. In the first guidance titled “Lupus Nephritis Caused By Systemic Lupus Erythematosus –Developing Medical Products for Treatment,” the document provides information for sponsors in the clinical development of medical products for the treatment of LN caused by SLE. Specifically, the document addresses study population enrollment and efficacy endpoints for LN trials. Other changes that were made include the addition of more specific examples of trial design and study endpoints, updating the science, and minor editorial changes to clarify specific issues. Input was obtained from the Center for Biologics Evaluation and Research and the Center for Devices and Radiological Health.

In the second guidance titled “Systemic Lupus Erythematosus –Developing Drugs for Treatment,” the agency discusses the indications that it may be willing to approve at present for new drug therapies for lupus. According to the FDA, progression to end-stage organ involvement continues, because many patients have incompletely controlled the disease, and current therapies and treatments carry potential risks of debilitating side effects. The agency noted the importance of clearly describing acceptable endpoints for approval to facilitate the development of novel therapeutic agents that would have the potential to be more effective or less toxic. Specific topics discussed in the guidance include: (1) measurement of lupus disease activity and clinical outcomes; (2) reduction in disease activity and flares; (3) treatment of organ-specific disease; (4) trial design issues and analysis; (5) surrogate markers as endpoints; and (6) risk-benefit assessment. FDA Notices, ¶42,034 (lupus neprhitis) and ¶42,035 (systemic lupus)


Opioid precursor designated for Schedule II control

The precursor chemical, 4-anilino-N-phenethyl-4-piperidine (ANPP) will be designated by the Drug Enforcement Administration (DEA) as an immediate precursor for the Schedule II controlled substance fentanyl and listed as a Schedule II substance under the Controlled Substances Act. According to the DEA, ANPP is the immediate chemical intermediary in the synthesis process currently used by laboratory operators for the illicit manufacture of fentanyl. Fentanyl produces opioid effects that are indistinguishable from morphine or heroin, but has a greater potency and a shorter duration of action. Fentanyl is a dangerous substitute for heroin because the amount that produces a euphoric effect also induces respiratory depression. The designation will assist in preventing the possible theft of ANPP from legitimate pharmaceutical firms where it is a chemical intermediary generated for fentanyl production. As a schedule II substance, ANPP will be safeguarded to the same degree that pharmaceutical firms now safeguard the fentanyl produced. The final rule is effective August 30, 2010. DEA Notice, ¶40,402


III. Food Developments

Nutritional labeling public docket opened

A public docket to solicit comments, data, and other information helpful to the implementation of §4205 of the Patient Protection and Affordable Care Act of 2010, (PPACA) (PubLNo 111-158) enacted on March 23, 2010, was established by the FDA. The new PPACA section amends §403 and requires chain restaurants and similar retail food establishments with 20 or more locations doing business under the same name and offering for sale substantially the same menu items to disclose nutrient content information for standard menu items appearing on restaurant menus and menu boards. PPACA also requires vending machine operators that own or operate 20 or more vending machines to disclose nutrient content information for certain articles of food sold from vending machines. The FDA is required to consider standardization of: (1) recipes and methods of preparation, reasonable variation in serving size and formulation of menu items, space on menus and menu boards, inadvertent human error, training of food service workers, variations in ingredients, and other factors as the Secretary determines; and then must (2) specify the format and manner of the nutrient content disclosure requirements. The FDA is tasked to promulgate regulations carrying out the provisions no later than March 23, 2011.

Specifically the FDA is seeking comments on an variety of topics including: (1) current practices within the restaurant or similar retail food establishment industry with respect to standard and non-standard menu items and the use of menus or menu boards; (2) methods related to presentation of nutrient content (ranges, averages, or other methods) for standard menu items that come in different flavors, varieties, or combinations but which are listed as a single menu item, such as soft drinks, ice cream, pizza, etc., or combination meals such as children’s combination meals; and (3) possible mechanisms for displaying products’ “nutrition facts” panels or otherwise providing visible nutrition information at the point of purchase. Submit written or electronic comments by September 7, 2010. FDA Notice, ¶43,913

Antimicrobial drugs in food-producing animals draft guidance published

A draft guidance with the FDA’s recommendations on the use of medically important antimicrobial drugs in food-producing animals has been published by the agency. Titled “The Judicious Use of Medically Important Antimicrobial Drugs in Food- Producing Animals, “the draft guidance summarizes key scientific reports on the use of antimicrobial drugs in animal agriculture and outlines the FDA’s current thinking on strategies for assuring that medically important antimicrobial drugs are used judiciously in food-producing animals in order to help minimize antimicrobial resistance development. In general, antimicrobial new animal drug applications can be divided into two broad categories: (1) new animal drug applications (NADA) submitted after the issuance of a 2003 guidance (GFI #152) and for which FDA is assessing the microbiological safety of the new animal drug on a pre-approval basis using the principles outlined in GFI #152; and (2) NADAs approved before the final version of GFI #152.

The second category of products are those antimicrobial NADAs that were approved prior to the implementation of GFI #152, some as many as 30 years ago, when antimicrobial resistance was not a concern. Because of this, the FDA is recommending two additional principles about the appropriate or judicious use of medically important antimicrobial drugs in food-producing animals: (1) ones considered necessary for assuring animal health; and (2) ones including veterinary oversight or consultation. Submit either electronic or written comments on the draft guidance by August 30, 2010. FDA Notice, ¶42,037

IV. Device Developments

Q & A guidance issued on IVD studies

A guidance document, written in question and answer format, has been issued by the FDA to assist manufacturers, sponsors, and applicants in the development of in vitro diagnostic (IVD) studies, particularly those exempt from most of the requirements of the investigational device regulations. The guidance will also help investigators who participate in IVD studies and institutional review boards that review and approve such studies. Titled “In Vitro Diagnostic (IVD) Device Studies –Frequently Asked Questions, “the guidance: (1) provides an overview of the regulatory framework pertaining to the development phase of IVD devices; (2) outlines FDA regulations applicable to studies for investigational IVD devices, including those regulations related to human subject protection; (3) explains data considerations that ultimately will affect the quality of the premarket submission; and (4) includes a glossary, a reference list with related web addresses, and a quick-reference table.

The information contained in the guidance applies to Class I, II, and III IVD devices regulated by either the Center for Devices and Radiological Health or the Center for Biologics Evaluation and Research. The guidance cautions that some devices used to test blood donor suitability are regulated as biologics and licensed under biologic regulations rather than under device regulations. The guidance applies only to IVD devices that are approved or cleared under device regulations, regardless of which center reviews the submission. The FDA received one comment on the earlier draft guidance of the same name, regarding the use of investigational IVD devices in clinical drug trials, which was outside the scope of the guidance. The FDA made several minor wording changes to improve clarity, but no substantive changes were made between the draft and final guidances. FDA Notice, ¶19,550