22 June 2012
Drug Safety Overhaul Advances in House and Senate
The Senate approved on 25 May the Food and Drug Administration Safety and Innovation Act (S. 3187), a wide-ranging bill that includes provisions aimed at improving the safety of imported drugs. The House of Representatives passed similar legislation (the FDA Reform Act, H.R. 5651) on 30 May, and a conference to resolve differences in the two measures is expected later this summer. The White House has signalled that President Obama will sign the final bill, which will follow similar regulatory overhauls for imports of consumer products (the Consumer Product Safety Improvement Act) and foods (the FDA Food Safety Modernization Act).
Facility Registration. S. 3187 would require electronic annual registration by foreign facilities that manufacture, prepare, propagate, compound or process drugs by deeming drugs from an unregistered facility misbranded. Information submitted at registration would include (i) with respect to drugs, a unique facility identifier and point-of-contact e-mail address as well as similar information about each drug importer and the importer’s establishments, and (ii) with respect to medical devices, the name of each U.S. importer known to the establishment and the name of each person who imports or offers for import such device to the United States.
H.R. 5651 would require commercial drug importers to include in their registration a unique identifier for their principal place of business.
Entry Restrictions. Under both bills the FDA would be required to carry out foreign drug facility inspections according to a schedule based on various risks, including the compliance history of the facility; the record, history and nature of recalls linked to the facility; the inherent risk of the drugs associated with the facility; and whether the facility has been inspected within the preceding four years. U.S. Customs and Border Protection, upon request from the FDA, would be required to deny entry to a drug product manufactured in an establishment that has refused to permit an FDA inspection.
Both measures would also authorise the FDA to require the electronic submission of certain information by a drug importer as a condition of granting entry. Such information could include regulatory status (e.g., new drug application), facility information (e.g., proof of registration or unique facility identifier), and inspection and compliance information. The FDA would have to take into consideration the type of import, such as whether the drug is for use in preclinical or clinical investigation.
Under the House bill, the FDA would be able to require the destruction without opportunity for export of any drug that has been refused admission and has a reasonable probability of causing serious adverse health consequences or death.
Expedited Entry. H.R. 5651 would require the FDA to issue regulations establishing good importer practices that specify the measures an importer should take to ensure that imported drugs are compliant with applicable requirements. The FDA would be able to provide expedited clearance for drug importers that volunteer to participate in partnership programmes for highly compliant companies.
Supply Chain Security. Lawmakers are still working to develop language giving the FDA authority to establish a uniform, comprehensive national system to secure the pharmaceutical distribution supply chain.
Increased Penalties. Under S. 3187 the penalty for knowingly and intentionally adulterating a drug if the drug has a reasonable probability of causing serious adverse health consequences or death to humans or animals would be increased to not more than 20 years imprisonment, a fine of not more than US$1 million or both. In addition, the penalty for knowingly and intentionally committing certain prohibited acts related to forging and counterfeiting of drugs, including selling and dispensing, would be increased to not more than 20 years imprisonment, a fine of not more than US$4 million or both.
H.R. 5651 would also impose a 20 year prison sentence for drug counterfeiting, along with a fine in accordance with title 18 of the U.S. Code, except that this term could be increased up to life if the counterfeit drug is the proximate cause of death of a consumer.
Extraterritorial Enforcement. S. 3187 would subject extraterritorial violations of the Federal Food, Drug and Cosmetic Act to enforcement in the U.S. if either (i) the article related to the violation was intended for import into the United States or (ii) an act in furtherance of the violation was committed in the United States.
Counterfeit Drugs. The Senate bill would allow the FDA to require notification by persons required to register as establishments engaged in the manufacture, preparation, propagation, compounding or processing of a drug, as well as persons engaged in wholesale distribution, if they know (1) of a substantial loss or theft of the drug or (2) the drug has been or is being counterfeited and the counterfeit product is either in U.S. commerce or is offered for import into the United States. Failure to notify the FDA would be a prohibited act and thus subject to penalties.
Generic Drugs. Both the House and Senate bills would authorise a new generic drug user fee programme, allowing the FDA to collect fees from industry to support human generic drug approval activities. Among other things, the bill provides for risk-based biennial inspections, parity of domestic and foreign inspection schedules by fiscal year 2017, a US$15,000 to US$30,000 higher inspection fee for a foreign versus domestic facility to reflect cost differences, streamlined hiring authority, and annual performance and fiscal reports. The generic drug user fee authority would sunset on 1 October 2017.
Third-Party Audits. The FDA would be required by S. 3187 to establish within two years an accreditation system, to include the recognition of accreditation bodies and the development of model standards, for third-party auditors to conduct drug safety and quality audits that may be used to certify compliance with good manufacturing practices, documentation requirements at the border and other purposes. The FDA would use the results of these audits to inform its drug risk-based inspection schedule.
Sharing of Trade Secret Information. S. 3187 would protect drug-related information obtained by the FDA from disclosure under the Freedom of Information Act and other laws when such information is provided by a federal, state, local or foreign government agency that has requested that the information be kept confidential. In specified circumstances, however, the FDA could share certain drug-related trade secret information through written agreement with foreign governments that it has certified as able to protect trade secret information from disclosure.
The bills have been endorsed by several industry groups but have faced moderate scepticism from consumer groups. On the one hand, the Consumers Union acknowledged in a 24 May press release that the Senate bill “includes some improvements over current law” but still has “significant flaws with the FDA’s current medical device oversight system in place.” This organisation believes that language should be added to the legislation to prohibit medical devices with known safety problems from being used as the basis for clearing new devices. In addition, the Consumers Union favours a national registry for tracking medical implant problems as well as enhanced FDA authority to rescind clearance of a device when a manufacturer fails to comply with an order to conduct a post-market safety study or when a post-market study reveals safety and effectiveness problems. Moreover, the association argues that the Senate legislation weakens current standards for preventing conflicts of interest on FDA panels that review medical devices and prescription drugs.
The Consumers Union believes that the legislation approved by the House is weaker than the Senate version because it does not include a provision to improve medical device safety before those products reach consumers. Provisions supported by this association that are not included in the House bill include (i) language to allow the FDA to more easily re-classify problematic devices so that subsequent, similar devices will receive more scrutiny before they get to patients; (ii) a timeframe for implementing proposed regulations on unique device identifiers; (iii) language to codify the requirement that approval for high-risk devices is contingent on completing required post-market studies; and (iv) a timeline on post-market studies for devices that had been cleared in the fast track 510k process.
By contrast, the Biotechnology Industry Association (BIO) lauded the passage of the Senate legislation, describing it as a bi-partisan effort that “will continue to ensure patient safety, access to the newest cures and therapies, and job growth in America.” BIO notes that the legislation “reflects enhancements” agreed upon by industry and the FDA and “will enhance the development and review of innovative new therapies through increased transparency and scientific dialogue, advancements in regulatory science and strengthened post-market review.”
For its part, the Pharmaceutical Research and Manufacturers of America also expressed support for the Senate and House versions of the legislation, noting in a 30 May press release that the reform effort will “provide FDA the resources necessary to help build new scientific and regulatory capabilities, support patient safety and promote ongoing biopharmaceutical innovation.”