Key to implementing the FDA Safety and Innovation Act (FDASIA) of 2012 is for FDA to issue new regulations and guidance that will help manufacturers understand how the agency aims to strengthen oversight of today’s global drug industry. Title VII of FDASIA provides added authority for FDA to inspect drug-production facilities; to block import of adulterated and substandard medical products; to require adherence to manufacturing standards; and to crack down on violators.
Agency leaders marked the first anniversary of FDASIA at a public meeting on July 12, 2013. The meeting updated industry on how the new policies will affect operations and ensure a more level playing field between suppliers and manufacturers at home and abroad. It also gave all parties an opportunity to comment on agency proposals for strengthening FDA authority over drug imports. FDA commissioner Margaret Hamburg opened the meeting by noting the importance of collaborative efforts with other regulators, with industry, and with crucial stakeholders in better securing a “more complex and more global supply chain.
Most notable was her announcement of a new proposed rule and a draft guidance document, the first of several such documents required to flesh out the FDASIA policies.
John Taylor, counselor to the commissioner and now acting deputy commissioner for global regulatory operations and policy, similarly noted the vast increase in countries, importers, and foreign facilities that produce FDA-regulated therapies. Title VII provides FDA with stronger tools to use against firms that refuse inspections or seek to import noncompliant products. And stiffer penalties for drug counterfeiting have been authorized by the US Sentencing Commission to go into effect in November 2013.
Additional data and information on facilities and operations will support a more effective system for targeting inspections and oversight of imports. These data are important for implementing Title VII’s various programs and requirements, explained Susan de Mars, senior advisor to the Office of Global Regulatory Operations & Policy. All manufacturing establishments now have to register with FDA and provide unique facility identifiers (UFIs) that will populate an electronic database able to track manufacturer operations, identify importer compliance, and generate information related to lost, stolen, or counterfeit products.
FDASIA’s provisions enhance partnerships and collaboration with foreign regulators, making it easier for FDA to exchange confidential information with peer regulators. The agency gains flexibility to recognize or rely on inspections of other regulators, which can help extend FDA’s limited resources, de Mars noted. FDA has been engaged in several inspection collaborations, and the legislation should lead to more formal recognition and mutual reliance on foreign government inspection findings.
A key FDASIA goal is to strengthen FDA’s authority to inspect manufacturing facilities in the US and abroad. By eliminating the traditional requirement that FDA inspect domestic drug facilities every two years, the legislation supports a shift to a risk-based inspection system that targets high-risk firms. FDASIA also authorizes FDA to examine facility records electronically and in advance of a site visit, which can help the agency determine whether or not to actually conduct the inspection at that time.
If FDA determines during an inspection that certain drugs may be adulterated or misbranded, it now can detain those products, instead of waiting for a court order to do so, which can give unscrupulous operators a chance to distribute the violative products. FDA describes how it will implement this new policy in a proposed regulation, which is similar to the policy already in force for medical devices and food (1).
New draft guidance further clarifies how FDA plans to conduct full and complete inspections of factories, warehouses, and other facilities involved in drug production (2). The guidance spells out how firms that delay, deny access, or limit inspections may have their products deemed misbranded and adulterated and not fit for sale in the US. The document lists prohibited behaviors that could delay the scheduling of inspections or an inspection in process, such as failure to produce requested records in a timely manner. And it spells out how manufacturers can run into trouble by preventing an inspector from beginning or completing a site visit.
FDA specifies that its agents have the right to access and copy records and to collect product samples as needed, including samples of finished products, raw materials, in-process materials, reserve samples, and environmental samples.
One notable paragraph states that FDA inspectors have authority to photograph facility conditions, an issue that has been the subject of heated legal debate for years. Lawyers already are questioning whether FDASIA actually does permit agency officials to use cameras during an inspection, and Doug Farquhar of Hyman, Phelps & McNamara speculates in the FDA Law Blog whether a company that refuses to permit photography will end up as a test case in court (3). FDA would like to receive comments on the guidance by Sept. 13, 2013.
A main purpose of the July public meeting was to provide manufacturers and other stakeholders with an opportunity to comment on FDA proposals for setting standards for imports, for registering commercial importers, and for devising good importer practices (GIPs). FDA expects GIPs to address registration requirements for commercial importers, exemptions (possibly for research products) to importer regulation, and the importance of importers meeting broader compliance standards, such as GMPs or demonstrating a satisfactory inspection history. One issue, noted FDA senior policy advisor Brian Pendleton, is whether importers should be required to establish drug-safety management programs as part of GIPs.
There was discussion about how useful a certificate of analysis is in documenting product authenticity, or if these forms are too easily falsified. The United States Pharmacopeia Convention (USP) proposed that compendia standards serve as a key marker for importer compliance. Excipient producers requested an exemption from import restrictions, noting that foreign producers ship large quantities of excipients to the US for a broad range of uses, making it impossible to segregate out those products specific to pharmaceutical production.
Another important topic is whether to permit compliant importers to qualify for expedited clearance procedures. US manufacturers would like to see risk-based standards for those importers that meet high standards, noted Sarah Spurgeon, assistant general counsel at the Pharmaceutical Research and Manufacturers of America (PhRMA). Industry representatives also proposed that GIP requirements might differ based on the type of drug imported, company inspection history, and evidence of supply-chain controls.
The globalization of drug production is a positive development, in that manufacturers can make products anywhere and market them worldwide via the Internet, noted John Taylor. But FDA “can’t just do more inspections and more examinations of imports,” he said. Instead, the agency needs to engage in inter-agency activities within the US and collaborate more with international regulatory and health organizations. FDA will be issuing a number of regulations and guidance documents to implement its new programs and is looking for manufacturers to help weigh all the options.
1. Federal Register, Vol. 78, No. 135, pp. 42382-6 (July 15, 2013).
2. FDA, Circumstances that Constitute Delaying, Denying, Limiting or Refusing a Drug Inspection, draft guidance (July 12, 2013), www.fda.gov/RegulatoryInformation/Guidances/ucm122044.htm, accessed Aug. 2, 2013.
3. Farquhar, www.fdalawblog.net (July 18, 2013).
About the Author
Jill Wechsler is BioPharm International’s Washington editor, Chevy Chase, MD, 301.656.4634, firstname.lastname@example.org. Read Jill’s blogs at www. PharmTech.com/wechsler.