FDA and Justice Department Address Drug Quality Concerns - Pharmaceutical Technology

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FDA and Justice Department Address Drug Quality Concerns
More collaboration and expanded oversight aim to compel manufacturers to follow GMPs.


Pharmaceutical Technology
Volume 36, Issue 2, pp. 24-28

Seeking partners

The generic-drug user-fee program also calls for FDA to use inspection information and reports from foreign regulatory authorities where appropriate, an approach championed by Sklamberg and others as a way to extend FDA's oversight capabilities. Several collaborative programs have been tested, and more are being implemented.

In December 2011, FDA and EMA announced a new GMP inspection initiative that calls for sharing information on drug-manufacturing inspections in their respective regions Under this program, which began last month, FDA will defer or waive routine GMP inspections of European facilities previously inspected by central or nationally authorized inspectorates, and EU member states will conduct fewer inspections in the US. While preapproval inspections will continue as needed, repeat GMP inspections may be avoided for manufacturers of less risky products, sites with few quality defects in the past, recently inspected facilities, and when there is an "urgent public health need," such as a drug shortage, that requires fast regulatory action. Both parties will keep track of the number of inspections deferred or waived and review the program after three years. Not only does the initiative aim to save resources for the regulators, but fewer inspections should reduce the compliance burden on manufacturers.

This new collaboration follows a successful joint inspection program for APIs, which involves FDA, EMA, and Australia's Therapeutic Goods Administration, along with specific EU member states. Launched as a pilot program in 2008, the initiative prevented many duplicate inspections of facilities and established a master list of API supply facilities, as outlined in a report issued in May 2011. Inspectors from the three regions shared information on more than 100 facility inspections, which helped identify weaknesses in manufacturer quality management systems and requested corrective actions. In some cases where inspection reports indicated satisfactory operations, a planned inspection involving the same API could be postponed or canceled. Participants also entered information from past inspections of more than 640 sites of mutual interest into a central database, thereby providing valuable information on site location, APIs produced, date and outcome of most recent inspection, and plans for future inspections by participating authorities.

The API pilot also involved a small number of joint inspections, which helped build confidence in each other's operations, but required considerable effort and time to organize and to evaluate. Now, the collaboration is expanding to include additional EU member states, and possibly more regions in the future. To further improve the program, participants hope to streamline management of the master list, devise a common inspection report format for joint inspections, and develop a common risk-based policy regarding re-inspection of sites located in third countries.

FDA and EMA are looking to extend the benefits of these joint regulatory efforts to streamline the review of manufacturing data in drug applications. In March 2011, the two agencies launched a collaborative review process for quality-by-design (QbD) components of new drug applications (NDAs), marketing authorization applications (MAAs), and supplements (referred to as variations in Europe). The two agencies hope to attract sponsors filing at the same time in both regions by striving for a consistent and efficient assessment of the quality/CMC sections of applications. Drug manufacturers also stand to benefit from joint early consultations that can yield harmonized advice; each agency, however, will issue its own review or report on the submission to meet domestic legal requirements.

This initiative builds on other FDA–EMA coordination efforts such as the joint inspection pilot for preapproval inspections for new drugs, which failed to gain strong support from the industry. In 2009, the regulators asked drug manufacturers planning simultaneous submissions in both regions to request joint preapproval inspections as a way to facilitate the application-review process. But only two joint inspections were performed, according to a report on EMA–FDA interactions issued by the agencies in June 2011. Observers note that the program was limited to drugs (not biologics), and that few companies planned simultaneous submissions. The new QbD review collaboration, which also excludes biologics, can provide joint preapproval inspections as part of the review process and appears to be attracting more interest from manufacturers.

Part of PIC/S

Another forum for promoting collaboration and harmonization of drug inspection practices and GMP standards is the Pharmaceutical Inspection Cooperation Scheme (PIC/S), which FDA formally joined in January 2011, after a five-year vetting process. Founded in 1970 by 10 European countries, PIC/S now has 40 members around the world, with Slovenia being the latest addition. Japan and South Korea have applied for admission; the Philippines, Indonesia, Taiwan, Iran, and New Zealand are moving forward in the application process; and China and India are planning to apply.

Previously a sideline observer, FDA now can play an active role in PIC/S programs to train GMP inspectors, establish risk-based quality standards, and share "rapid alerts" on drug safety problems, explained Brenda Holman, head of ORA strategic initiatives, at the PDA/FDA conference last September. Holman described how FDA can help develop PIC/S guides for meeting GMPs for drugs, APIs, vaccines, blood and blood products, and biotechnology-derived drugs as part of international collaborations to provide more effective market surveillance on a global scale.

As with its members, PIC/S faces challenges in dealing with increased outsourcing by manufacturers and more complex biopharmaceutical supply chains, Holman noted. Regulators are dealing with this by teaming up for joint inspections to conserve resources as well as to build confidence in the operations of other regulatory bodies. PIC/S is encouraging inspection plans based on risk evaluation and is looking to expand into other relevant fields, such as oversight of good clinical practices and good distribution practices, the latter item reflecting growing supply-chain concerns.

Although PIC/S policies are not legally binding, information from fellow regulators on a previous site inspection may lead FDA to forego its own site visit, and other PIC/S members can avoid duplication by relying on FDA inspection reports. FDA also can gain information on how other inspectorates rank sites for risk and compliance status, future inspection schedules, and common practices involving the scope, format, and duration of site visits.

Jill Wechsler is Pharmaceutical Technology's Washington editor, 7715 Rocton Ave., Chevy Chase, MD 20815, tel. 301.656.4634,


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