Moving to Risk-Based Inspections - Pharmaceutical Technology

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Moving to Risk-Based Inspections
The author discusses the key provisions of GDUFA as they relate to the pharmaceutical supply chain, including parity of inspections between domestic and foreign sites for both finished dosage forms and APIs of generic drugs.

Pharmaceutical Technology
Volume 36, Issue 9, pp. s30-s32

Industry response

Industry response to the GDUFA has been largely positive with groups, such as the Generic Pharmaceutical Association (GPhA), the European Fine Chemicals Group (EFCG), and the Bulk Pharmaceuticals Task Force (BPTF), an affiliate of the Society of Chemical Manufactures & Affiliates (SOCMA), supporting the passage of the GDUFA and offering input throughout the legislative process.

"The historic user-fee legislation—the most important pharmaceutical legislation since the 1984 Hatch-Waxman Act—will provide FDA with additional resources and ensure all participants in the US generic-drug system, whether US-based or foreign, comply with our country's strict quality standards," said Ralph G. Neas, president and CEO of GPhA, in a July 9, 2012, GPhA press release. The new fees are expected to reduce the average review time for most generic-drug applications by nearly two years—from more than 30 months today to 10 months by the end of the program's fifth year, according to GPhA, and will provide increased funding for generic-drug manufacturer facility inspections.

For fine-chemical and API producers, one of the key provisions of the GDUFA is the adoption of a risk-based inspection process to achieve parity in facility inspection between US and foreign manufacturers, a point made by FDA Commissioner Margaret Hamburg earlier this year (3). "Under the GDUFA, FDA will also ensure that manufacturers—foreign or domestic—who participate in the US generic drug market are held to the same, consistent, high quality standard," said Hamburg at the GPhA Annual Meeting on Feb. 23, 2012 (3). "We will conduct risk-adjusted biennial surveillance inspections of all generic API and finished form manufacturers—with the goal of achieving parity of inspection frequency between foreign and domestic firms by year five. Having the resources to undertake these regular inspections will level the playing field for foreign and domestic manufacturers..."(3).

The fine-chemicals industry agrees. "The Congressionally mandated inspection frequency of every two years has been very difficult to achieve due to insufficient resources within FDA and the rapid globalization of generic-drug manufacturing," says BPTF Executive Director John DiLoreto. "While US facilities have been inspected approximately every 2.5 years, many foreign facilities have never been inspected at all. Successful implementation of the GDUFA will result in the identification and registration of all drug-production facilities," he explains. "Previously, FDA even had difficulty determining how many facilities were producing generic drugs that enter the supply chain every day," he said. By the end of the first five years of the GDUFA, it is expected that all foreign and domestic facilities will be inspected at the same nominal rate of every two years. "This will level the playing field for foreign and domestic producers and establish a balance in drug quality by ensuring that all manufacturers are implementing cGMPs," says DiLoreto.

Under the GDUFA, FDA will conduct risk-adjusted biennial cGMP surveillance inspections of generic API and generic finished dosage-form manufacturers, with the goal of achieving parity of inspection frequency between foreign and domestic firms in FY 2017. FDA will prioritize inspections of establishments associated with ANDAs that are otherwise approvable or eligible for tentative approval except for an outstanding inspection, as well as establishments associated with ANDAs that have not been inspected previously. In appropriate circumstances, FDA can rely on a routine surveillance inspection in lieu of an application-specific inspection. Generally, FDA relies on a previous inspection of a finished product site occurring within two years of the cGMP evaluation for a pending application, three years for an API site or a control testing laboratory, and four years for a packaging-only site (2). There are exceptions to this general practice, which are usually related to the nature of the drug being processed or the complexity of the associated processing operations. Under the GDUFA, FDA intends to continue the practice of using a risk-based assessment in determining the length of time since the last inspection, guided by a two-year cycle for finished dosage product sites and a three-year cycle for API sites with consideration of the type of finished product or API in the application. For making decisions about pending applications for which FDA does not have current inspection information within the time period indicated, FDA may use previous FDA inspection information and/or use inspection information from another regulatory authority as appropriate (2).


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