FDA and European Commission consider complementary approaches to deregulate variations

The FDA and European Union are both undertaking significant programmes of work to lighten the regulatory burden on the industry in the case of variations. Updates were given to TOPRA Symposium delegates in Budapest.

Martin Terberger, Head of Unit F2 Pharmaceuticals, European Commission, stated that he was particularly pleased that this was a transatlantic session and that it should bring both bodies closer together, thereby reducing the ‘distance between them.’

Dr. Norman Schmuff of the FDA also expressed pleasure at the opportunity to present an FDA perspective of the Post-Approval Regulatory initiatives that the FDA is currently undertaking.

Dr. Terberger began by giving an in-depth account of the European Commission’s efforts as part of a two-year consultation and deliberation process to replace Regulations (EC) No 1084/2003 and 1085/2003.
The objective is to be clearer, simpler and more flexible in a way that lessens the administrative burden for industry without any compromise to human or animal health.

There were five main objectives to the proposed reforms. Firstly, harmonisation of all variations—not just those done through European processes, which account for only 16% of all variations. Secondly, using the concept of design space with a direct reference to ICH Q8 as an EMEA guideline. Thirdly, the shift from ‘Tell and Do’ to ‘Do and Tell’. According to Dr. Terberger’s own analysis of recent cases, this may result in up to a 77% reduction in obligations in comparison to the current arrangements. Fourthly, promoting work-sharing. Fifthly, changes to guidance on definitions which would make type IB the default option, with the option for the competent authority to switch to Type II procedure in certain circumstances. Conditions for classification would still be located in the Annex, but there would also be Commission Guidelines and EMEA scientific recommendations.

Taken together these have the potential to significantly lessen the obligations on National Competent Authorities and the industry while taking a more risk-based approach to variations. Dr. Terberger advised that we are likely to see the concluding steps in both the Comitology and Co-decision streams in the next couple of months.

Dr. Schmuff gave an FDA perspective of how the agency has sought to amend Federal Regulation 21 Code 314.70 by introducing ICH Q8 as guidance. This gives greater flexibility as the level of scientific information increases and there is more reliance on chemical manufacturing processes. It allows for broader discussions on levels of risk and reduces necessity for post-approval submissions. However, this is only possible if proactive risk management runs throughout the process, including well into post-authorisation.

The FDA encourages firms to formulate a Post-approval Management Plan (PMP). This has resulted in de-regulation on a number of things, including both in-development and post authorisation testing and reporting for post-approval changes. Dr. Schmuff offered a few examples and concluded by stating that the FDA is seeking to fundamentally influence pharmaceutical manufacturing to rely more on product-knowledge and process understanding-led quality control strategies. But with this risk based approach, management would have to take responsibility for ensuring the right outcomes.

The session was closed by respondents from industry, TOPRA, and the American Association of Pharmaceutical Scientists. Respondents in the panel discussion were very supportive of this shift by the FDA and the European Commission and indicated their willingness to work closely and be collaborative with both authorities.

New TOPRA President Alan Hunter said,

‘This excellent session shows how facilitating the dialogue between industry and authorities can lead to positive results for industry and agencies. We were delighted to have the FDA and the European Commission on the same panel to talk about their work in this area. We look forward to more opportunities like this for TOPRA to act as a key communications channel.’