When international regulatory authorities get together, what private discussions take place? This was the premise of a talk by Janice Soreth, MD, Deputy Director of FDA’s Europe Office, at the AAPS annual meeting in New Orleans on November 17. The talk was titles, “Globalization of Pharmaceutical Regulation: What Do Agencies Discuss Behind Closed Doors?”

FDA’s international relationships go as far back as the 1940’s, Soreth noted. Today, FDA has more than 100 bilateral agreements with other regulators, though most are non-binding.

Confidentiality Agreements

Soreth began by discussion Confidentiality Agreements, the single largest group of FDA’s international arrangements. Over half of these are with EMA and other European authorities, she noted. The agreements do not commit either party to anything, but are rather aimed at facilitating idea and information exchange.

Confidentiality Agreements allow FDA to exchange non-public information with foreign counterparts. “Non-public” includes commercial confidential, investigative, and pre-decisional information, or preliminary thinking as guidances and policies are developed, she said.

The commitment part is that both agencies agree not to disclose publicly what is shared. FDA cannot share personal patient data or critical trade secrets, but “we of course do not like to blindside our regulatory partners, and we like to give them information so that they can get their ducks in a row” before information and issues become public.

The pandemic flu is a prime example of such sharing. To be prepared for the H1N1 outbreak, FDA wished to investigate data for extension of expiry dating, so it approached the companies manufacturing flu vaccines, and requested and received permission to have dialogue with European agencies about whether these medicines could be used beyond expiry dates. Manufacturers were forthcoming with expiry-related information despite concerns over “trade secrets” and the sharing of proprietary information, she said.

API Inspection Pilot

Soreth next discussed the API Inspection Pilot with European and Australian regulators. The pilot, set for completion at the end of 2010, is one of three ongoing pilots between these parties. (The other two are a GMP pilot for finished drug products, and a good clinical practices pilot.)

The API Inspection Pilot was proposed in November 2007 in Brussels as an “effort to improve international sharing of information and to facilitate more risk-based approaches to inspection planning.” EMA and European authorities joined FDA and Australia’s TGA in this effort.

A small group of inspectors established the project to build on equivalent API GMP standards and foster mutual confidence between themselves. Starting in December 2008, there began the sharing of inspection plans and completed inspection reports from the previous 24-36 months. There was also then discussion about the future and where the authorities could partner and support each other—to increase transparency and visibility of inspections, and decrease duplicate inspections. “Where could we help overcome audit fatigue?” she explained.

A master list of past inspections was constructed. The three parties provided 1046 site entries: 499 from Europe, 352 from FDA, and 195 from TGA. (The report can be found on EMA’s website.) Of the roughly 500 sites inspected by European authorities, 190 (38%) were of interest to either of the other two authorities, FDA or TGA. Of those FDA-inspected sites, roughly half were of interest to EMA or TGA, and many of the TGA-inspected sites were of mutual interest to EMA and FDA.

The second phase of the pilot was to conduct joint inspections. A total of 7 joint inspections have been performed so far, with European authorities (EMA, EDQM) participating in six, five with TGA and one with FDA. FDA participated in two joint inspections, one with EMA and one with TGA. The lessons learned from these joint inspections are being developed as the project winds down at the end of 2010.

Some general learnings of API pilot, however, include:
•    There is an essential public health need to collaborate on regulation of global API sites.
•    Continuous collaboration is need to minimize duplicate routine inspections, and to increase the number of API inspections.
•    There is a clear need to “grow” the database of API manufacturing sites, and to have better tools (in order to automate “beyond Excel spreadsheets”).