Food, Drug & Devices – August 2010

Topic of the Month: An outbreak of Salmonella Enteritidis (SE) that sickened hundreds of people across the country led the FDA to a recall of shell eggs. On August 13, a major shell egg producer voluntarily conducted a nationwide recall of shell eggs on 3 of its 5 farms. Further epidemiologic and traceback information led to the producer expanding its recall on August 18 to cover all 5 farms and 380 million eggs. The FDA is currently monitoring the recall, including conducting audit checks at retail stores, wholesalers, and distributors to make sure the recalled shell eggs are being removed from the market. At the same time the recalls were issued, the FDA published a number of guidances in late August for industry on steps to avoid contamination of facilities used in the production and transportation of shell eggs.  Discussion of those guidances are expected to occur in September.

I. Agency Developments

Fiscal year 2011 veterinary drug fees established
The rates and payment procedures for fiscal year (FY) 2011 generic new animal drug user fees were established by the FDA pursuant to the FDC Act, as amended by the Animal Generic Drug User Fee Amendments of 2008 (AGDUFA, ¶2004), for abbreviated applications for generic new animal drugs, generic new animal drug products, and sponsors of such abbreviated applications for generic new animal drugs or investigational submissions for generic new animal drugs. The agency additionally published the FY 2011 animal drug user fees.

For FY 2011, the generic animal drug user fee rates are: $92,600 for each abbreviated application for a generic new animal drug; $5,440 for each generic new animal drug product; $55,950 for each generic new animal drug sponsor paying 100 percent of the sponsor fee; $41,963 for each generic new animal drug sponsor paying 75 percent of the sponsor fee; and $27,975 for a generic new animal drug sponsor paying 50 percent of the sponsor fee.
The Animal Drug User Fee Act of 2003 authorizes the FDA to collect user fees on: (1) animal drug applications, (2) animal drug products, (3) establishments where such products are made, and (4) sponsors of such animal drug applications or investigational animal drug submissions. For FY 2011, the animal drug user fee rates are: $316,200 for an animal drug application; $158,100 for a supplemental animal drug application for which safety or effectiveness data is required and for an animal drug application subject to certain criteria; $7,235 for an annual product fee; $83,100 for an annual establishment fee; and $64,000 for an annual sponsor fee. The FDA will issue invoices for FY 2011 product, establishment, and sponsor fees by December 31, 2010, and these invoices will be due and payable on or before January 31, 2011. The application fee rates are effective for applications submitted on or after October 1, 2010, and will remain in effect through September 30, 2011. Applications will not be accepted for review until the FDA has received full payment of application fees and any other animal drug user fees owed. FDA Notices, ¶43,918 (generic animal drugs) and ¶43,919 (animal drugs)

Prescription drug user fee rates for 2011 announced
Fiscal year (FY) 2011 prescription drug user fee rates, effective on October 1, 2010, through September 30, 2011, were announced by the FDA. Base revenue amounts for application fees, establishment fees, and product fees were established by the Prescription Drug User Fee Amendments of 2007 (PDUFA). Total fee revenue, as specified in PDUFA, is then adjusted by the FDA for additional drug safety amounts as well as for inflation and FDA workload. The fees for FY 2011 are as follows: (1) application fees for an application requiring clinical data ($1,542,000); (2) for an application not requiring clinical data or a supplement requiring clinical data ($771,000); (3) for establishment fees ($497,200); and (4) for product fees ($86,520). For applications and supplements that are submitted on or after October 1, 2010, the new fee schedule must be used. Invoices for establishment and product fees for FY 2011 will be issued in August 2010 using the new fee schedule.  FDA Notice, ¶43,920
II. Drug and Biologics Developments

Design of OTC label comprehension studies
Developers who design label comprehension studies for nonprescription drug product marketing should consider independent consumer behavior studies in their design process. In a guidance titled “Label Comprehension Studies for Nonprescription Drug Products, “the FDA provides recommendations on the design of label comprehension studies, which can be used to assess the extent to which consumers understand the information conveyed by proposed nonprescription drug product labeling. Label comprehension study data generally do not predict consumer behavior, e.g., how consumers actually use a drug product. The guidance recommends that the study include all subjects who can potentially use the drug product, regardless of age, sex, underlying medical conditions, and use of concomitant medications. Because nonprescription drug products are available for purchase without a learned intermediary, and since no drug product is administered in the study, exclusion factors such as the inability to understand English should be minimal and should be justified in the study protocol. The design of a label comprehension study should be an open-label, uncontrolled trial, and that qualitative research and pilot testing be conducted comparing different versions of the label prototypes before the larger label comprehension study is conducted

Label design studies can be requested by the FDA: (1) before the approval of a new drug product for the nonprescription market; (2) when one or more new indications, a new target population, or a new strength are proposed for a marketed nonprescription drug product; (3) when a substantive labeling change has been proposed for a marketed nonprescription drug product; (4) when drug products with new active ingredients that have a proprietary name associated with other active ingredients are proposed; and (5) when adequate consumer labeling for the drug product requires the inclusion of a package insert; comprehension testing of the insert may be needed. FDA Notice, ¶42,044

Comprehensive cosmetics safety bill proposed
On July 20, 2010, Representative Jan Schakowsky, (D-Ill.) introduced a bill in the U.S. House of Representatives that would require the FDA to regulate the ingredients in cosmetics. Titled “Safe Cosmetics Act of 2010, “the proposed bill would amend the FDC Act and provide for extensive authority and oversight be given to the FDA to regulate cosmetics. To provide for this oversight, the proposed bill would require an FDA-imposed fee schedule based on an establishment’s gross receipt of sales and would apply to all establishments with annual gross receipts or sales of more than $1,000,000. All establishments engaged in manufacturing, packaging, or distributing cosmetics for use in the United States, whether domestic or foreign, would be required to register with the Secretary annually under the proposed bill. Required registration would include:
(1) any information necessary to notify the Secretary of the name and address of each establishment at which, and all trade names under which the registrant manufactures, packages, or distributes cosmetics;
(2) a description of the establishment’s activities with respect to cosmetics;
(3) the number of workers employed at the establishment;
(4) the gross receipts of sales; and
(5) the name and address of any company that supplies the establishment, if the establishment manufactures cosmetics, with any ingredient (including preservatives, fragrances, or any other chemical component of a finished cosmetic product) and the name of the ingredient supplied to such establishment by such supplier.

The proposed bill would require that all cosmetics sold for retail have a declaration of the name of each ingredient, which has undergone safety testing, in descending order of predominance, with provisions and requirements for internet vendors to declare ingredients online. No later than one year after the date of the enactment the HHS Secretary would be required to establish minimum data requirements and test protocols to be used by manufacturers to assess the safety of cosmetic ingredients that would ensure that any statements regarding compliance with the safety standard are based on sufficient and reliable data.
The proposed bill also requires that no later than one year after the enactment of the “Safe Cosmetics Act of 2010,” manufacturers and distributors of cosmetics and ingredients must submit electronically all reasonably available information in the possession or control of the manufacturer or distributor that has not previously been submitted to the Secretary regarding the physical, chemical, and toxicological properties of single or multiple chemicals listed on the cosmetic labels. This submission would include:
(1) functions and uses;
(2) exposures and fate information;
(3) tests of finished cosmetics; and
(4) any other information used to substantiate the safety of the cosmetics and ingredients.

Under the proposed bill, no later than 12 months after the date of enactment the Secretary would publish a comprehensive, publicly accessible database containing all non-confidential information submitted by manufacturers and distributors. Furthermore, any ingredient or cosmetic that induces cancer or birth defects or has reproductive or developmental toxicity when ingested by, inhaled by, or dermally applied to a human or an animal would fail to meet the bill’s safety standards. The FDA would have the authority to require companies to specifically label “nano-scale” ingredients. The proposed bill would also require the Secretary to create a priority assessment list within 18 months of enactment of not less than 300 ingredients which cannot be included on the restricted and prohibited list, or the safe without limits list because of a lack of authoritative information on the safety of the ingredient, and for which safety determinations will be made. Companies would be prohibited from manufacturing, marketing, delivering or selling cosmetics or cosmetic ingredients if they failed to provide the FDA with the required information. The bill also contains provisions relating to: (1) market restrictions; (2) adulterated and misbranded products; (3) recalls; (4) mandatory reporting of adverse health effects; (5) animal testing alternatives; and (6) interagency cooperation and funding. The proposed legislation was referred to the Committees of Energy and Commerce, and Education and Labor. H.R. 5786, 111th Cong., 2nd Sess. (2010), ¶200,181

II. Food Developments
Voluntary PPACA registration for food establishments
Retail food establishments and vending machine operators not otherwise subject to the provisions of section 4205 of the Patient Protection and Affordable Care Act of 2010 (PPACA) (P.L. 111-158) may voluntarily elect to become subject to them, according to the FDA, pending promulgation of regulations. PPACA amends section 403 of the FDC Act by requiring 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. Restaurants with less than 20 locations may choose to voluntarily register, although they are not required to do so. Restaurants who do not voluntarily register will be subject to state and local nutrition and labeling regulations, which may not mirror the new federal laws, but by registering the entities would only be subject to the federal requirements. Vending machine operators would have the ability to avoid local requirements as PPACA expressly provides that no state or locality may have a requirement concerning vending machines that is not “identical to” the federal requirements, regardless of how many vending machines the operator owns or operates. Vending machine operators are still encouraged to voluntarily register.
The FDA will begin accepting voluntary registration on July 21, 2010, and registration must be completed on an annual basis. Authorized officials for restaurants and similar retail food establishments who wish to register must provide the FDA with the required information including: (1) the name, address, phone number, e-mail address, and contact information for the authorized official; (2) all trade names the restaurant or similar retail food establishment uses; and (3) certification that the information submitted is true and accurate, that the person or firm submitting it is authorized to do so, and that each registered restaurant or similar retail food establishment will be subject to the requirements of section 4205. Similar information for vending machine operators must be submitted, including the location of each vending machine operated by the registrant. FDA Notice, ¶43,916

Reportable Food Registry experiences discussed
A report discussing the FDA’s early experience with the Reportable Food Registry which opened in September of 2009, was published by the agency. Titled “A New Approach to Targeting Inspection Resources and Identifying Patterns of Adulteration: The Reportable Food Registry,” the report highlights the effects of the registry through March 31, 2010. The registry was created in 2007 and required the FDA to establish an electronic portal through which reports regarding instances of reportable food must be submitted to the FDA within 24 hours by responsible parties. These reports may be: (1) primary, the initial submission about a reportable food; or (2) subsequent, a report by either a supplier or a recipient of a food or food ingredient for which a primary report has been submitted. The registry covers all human and animal food and feed including pet food regulated by the FDA except infant formula and dietary supplements.
From September 8, 2009, to March 31, 2010, the registry logged entries in 11 different commodity categories regarding hydrolyzed vegetable protein (HVP), and resulted in 117 products containing contaminated HVP being recalled. The registry was also used successfully when a food manufacturing facility submitted a report notifying the FDA that two nationally distributed prepared side dishes had been inadvertently produced with an ingredient containing sulfites, which were not mentioned on the labels, and within three days the electronic portal received 108 subsequent reports from facilities that had received the implicated products. The manufacturers initiated a voluntary recall and no adverse events were reported. The registry had 2055 total submissions which contained 211 non-reportable submissions that dealt with drugs or foods under the U.S. Department of Agriculture’s jurisdiction. Thirty-seven percent of submissions dealt with Salmonella contamination, 35 percent dealt with undeclared allergens and 2 percent involved foreign object contamination.  Full text of the FDA’s report is available at ¶400,034. FDA Notice, ¶43,917

Shell egg Salmonella prevention draft guidance published
A draft guidance titled “Prevention of Salmonella Enteritidis in Shell Eggs During Production, Storage, and Transportation” published by the FDA provides information to egg producers on how to comply with certain provisions contained in the FDA’s final rule on shell egg safety, including how to implement Salmonella enteritidis (SE) prevention measures, how to sample for SE, and how to maintain records documenting compliance with the final rule. The agency recommends that multiple farms should not share equipment, but farms that do so should be thoroughly cleaned and disinfected. Additionally, only clean and disinfected crates, egg cartons, pallets, and other equipment should be brought onto a farm, and business should only be conducted with other companies that also have high biosecurity standards. FDA Notice, ¶42,047