FDA Inspections: Current Initiatives

The globalization of the pharmaceutical supply chain and the quality issues that have arisen because of that globalization, the FDA initiative "Pharmaceutical Quality for the 21st Century" and resource constraints that all Health Authorities are feeling are all changing the way FDA is viewing their mission to protect the American consumer.  Here is an overview about the current initiatives:

Development of the Pharmaceutical inspectorate: The Pharmaceutical Inspectorate is CDER's version of Team Biologics. While the program has existed since 2003, the FDA is just now starting to see a real impact from this program.  These investigators are all highly trained, Level III certified drug inspection specialists.  They perform both US and non US inspections of highly complex or high risk sites.  Because the members of this cadre are trained as a group, the variability on inspection conduct is decreased. 

Dedicated non US inspection cadre: FDA traditionally has had difficulty resourcing non US inspections.  The trips are very demanding on the investigators and there is / was little or no incentive to perform these inspections.  FDA is addressing this issue, in part, by the implementation of a dedicated non US inspection cadre of approximately 30 members.  These investigators only perform non US inspections, and are experienced not only in their program area, but in the logistical and cultural challenges of non US inspections.  Since they are managed out of the Office of Regional Affairs (ORA), they maintain a close relationship with both the Center contact and the FDA International Office of Compliance.

Issuance of an updated Compliance Program on Pre-Approval Inspections (CPGM 7346.832): The new program also harmonizes the performance of PAIs performed for both large and small molecules, taking the best aspects from both the CDER and CBER inspection models.  The program requires much more involvement of the NDA / BLA reviewers in the inspection process, and substantially increases the guidance around inspections of drug substance manufacturers.

Establishment of overseas offices: The goal of establishing liaisons in foreign countries is to provide support for development of regulatory capacity, promote information sharing and regulatory collaboration, administer certification and verification programs, and to facilitate and coordinate foreign inspections within a given country.  By obtaining useful information and intelligence from foreign regulatory counterparts, FDA will be able to more effectively analyze risk to target foreign inspection resources and inspections will be easier to facilitate, coordinate and conduct.

Resource sharing: Both the FDA and EU recognize that they inspect each others facilities too much, and that there are opportunities to leverage inspection information.  Initiatives such as Joint inspection Program are an attempt to begin this process.

PIC/S Membership: FDA has been accepted into the Pharmaceutical Inspection Co-operation Scheme (PIC/S),  which fosters cooperation among pharmaceutical inspection authorities and training of competent authorities (in particular inspectors.)  Upon acceptance, PIC/S membership will enable the exchange of inspection reports and other inspection information with regulatory authorities.  While the admission of FDA to PIC/S is an important milestone, there are still legal hurdles (see below) that must be overcome before FDA would be allowed to accept member nation inspections in lieu of their own inspections.  However, having access to member state inspection reports will allow FDA to make better risk based decisions regarding when a non US facility should be inspected.

New Proposed Legislation: There is currently legislation in front of Congress affecting the FDA.  Some of the draft legislation provisions include:

• A requirement for manufacturers to develop and maintain quality management plans subject to inspection by FDA,
• Maintenance of drug pedigrees throughout the supply chain,
• Development and implementation of a system to track drug substance and drug product manufacturers,
• Providing FDA the authority to mandate a recall of drug substance and drug products,
• A requirement that FDA provide a report on agreements it enters into with foreign regulatory authorities to mutually recognize assessments of industry compliance with manufacturing standards and
• Provides FDA authority to share information with other regulatory bodies.

And what is the future state?
FDA has stated publicly at several meeetings that they intend to significantly increase the number of non US inspections they perform in the coming years.  What the impact of that increase is to Europe is not yet clear.  As stated previously, both the FDA and the EMA have indicated that, based on their risk assessments, they inspect each other far too much and are looking for opportunities to leverage resources.  I believe you should not expect to see a significant increase in inspections within the EU, but will see a significant increase in China, India and other countries manufacturing drug substance and drug product for the US market that have not yet developed mature regulatory systems.

Dr Mark Tucker
F. Hoffman La Roche

(Part of an the Article "FDA Inspections: Past, Present and Future", to be published in the GMP Journal)

Mark Tucker is Senior Director, GMP Compliance at Genentech Inc (F. Hoffman La Roche Group)., South San Francisco, USA, where he has the full strategic responsibility for GMP Compliance. Before joining Genentech in 2002, Mark was Director, Investigations Branch at U. S. Food and Drug Administration (FDA).  He also served as an Investigator and Compliance Officer with the FDA, where he represented the FDA at meetings with firm management and industry groups outlining and defending FDA positions.
Mark will be a speaker at the ECA Course How to Pass EU and FDA Inspections and GMP-Compliance Audits on 25 - 27 May 2011 in Prague, Czech Republic.