Post-approval commitments and conditional authorisations
12-13th May 2005, Woodlands Park Hotel, Surrey, UK
Background
When a marketing approval is issued for a new medicine there are always certain statutory conditions and commitments, such as postmarketing surveillance of adverse drug reactions (ADRs) and labeling requirements that are applied routinely. The discussions at the Workshop convened by the CMR International Institute for Regulatory Science, in May 2005, however, focused on the post-approval commitments (PACs) that are applied selectively and agreed on a case-by-case basis, at the time of authorisation. Such PACs often require special studies to be carried out to confirm and supplement aspects of the technical data, such as the use of biomarkers and surrogate endpoints. The related subject was discussed of issuing ‘conditional authorisations’, which allow urgently needed medicines to be made available to patients early, but restrict full marketing until specific obligations have been fulfilled.
Different approaches
Speakers from FDA, EMEA and PMDA gave an overview of the different practices in the USA, EU and Japan. Under FDA procedures certain PACs are required by law or regulation (e.g., following accelerated review) whilst others are mutually agreed between the company and regulators during the review process. In the EU the legislation is undergoing changes that will modify and clarify the requirements for conditional authorisations and the procedures for accelerated assessments, where approval is almost inevitably associated with ‘specific obligations’ to carry out further studies. In Japan there are conditional authorisations and PACs but the picture is somewhat different in that there is a routine request for companies to collect information on all patients using the new medicine, for a fixed period or until a specified number of cases have been collected (‘complete count survey’).
Company survey
A survey was carried out by the Institute, in preparation for the Workshop which documented companies observations on the increased workload attributed to PACs and concerns about the usefulness of some of the studies that had been requested. Nonetheless companies recognised that they were a ‘valued regulatory tool that enables faster access to medicines by patients in a real-world setting’.
Syndicate discussions
The break-out groups, or Syndicates, at the Workshop were asked to discuss improvements to current procedures related to PACs and conditional authorisations and to look toward future changes that might streamline drug development and make new therapies more rapidly available to patients.
The following were included in the recommendations:
- The importance of early discussion between companies and authorities to avoid PACs becoming a last-minute issue in the late stages of review.
- The need for improved international cooperation between agencies to harmonise requirements for additional studies when reviewing the same product.
- Proposals for a Workshop to examine the potential role of large-scale, population-based databases of electronic health records (EHRs) as a source of post-marketing information on medicines.
- The need for constructive approaches to the ongoing challenge of communicating with, and educating, patients, politicians, the media and healthcare providers on issues relating to the benefit–risk balance of medicines.