A second industrial pharmacy session looked at new European legislation, focusing particularly on mutual recognition agreements (MRAs). The session, on September 14, was chaired by Mr John Jolley, and presentations were heard from Mr Mike Murray (Association of the British Pharmaceutical Industry) and Mr David Begg (David Begg Associates). Mr Murray discussed other current regulatory developments affecting the pharmaceutical industry, while Mr Begg reported on the progress of MRAs relating to good manufacturing practice inspections
There were a number of European regulatory proposals in the process of development which would affect the pharmaceutical industry, Mr Mike Murray (of the ABPI) said. All would result in "a lot of activity" for the industry. As well as mutual recognition agreements, there was a proposed starting materials directive (which aimed to apply the concepts of GMP to starting materials), a clinical trials directive (which would require release of clinical trials materials by a qualified person), regulations relating to the use in pharmaceutical products of materials derived from ruminant animals, and guidance relating to batch release and certification (which could affect who was responsible for the release of the final product under a variety of circumstances to the European Community market). |
Mike Murray: facilitate international trade |
Mr Murray said that as far as mutual recognition agreements were concerned, the industry agreed that MRAs would facilitate international trade and were part of an overall move towards international harmonisation of requirements for medicinal products. The process might take some time to move ahead, but the ABPI was basically supportive and was working towards helping achieve a reasonable system. Eventually, the inclusion of Japan and other countries, as well as Europe and the United States, in MRAs for GMP was expected.
Full texts of all the completed MRAs could be seen on the EC website (dg3.eudra.org).
On the subject of starting materials, Mr Murray said that the proposed starting materials directive would be going to the European Parliament shortly. It sought to apply the concepts of good manufacturing practice to starting materials. When first drafted in October, 1997, the proposal had applied only to a number of specified excipients, largely animal-derived products. However, the proposal had been revised in February, 1999, and as it now stood would apply to all starting materials. This could mean all excipients, which could pose difficulties for the industry. However, it was believed that the proposal was for a framework directive and that there might be a differential approach taken to different categories of starting material. The progress of the proposal would be followed closely.
Turning to the proposed clinical trials directive, Mr Murray said that the first Commission discussion document on clinical trials had been published in 1991 and had taken several years to develop to a formal proposal. This had had its first reading in the European Parliament in 1998, following which the draft directive had been amended in April, 1999.
The amended Commission proposal could be seen on the EC website (dg3.eudra.org/dgiiie3/news.htm).
Among other things, the directive would eventually require the release of clinical trial materials by a qualified person. One question was whether the qualified person, as currently trained, would be suitably equipped to act as the qualified person for clinical trials, or whether they would need different expertise. Could we see the emergence of "specialised" qualified persons for different activities? The development of this debate would be interesting.
Spongiform encephalopathies
In 1997 the European Commission, following the concerns regarding transmissible spongiform encephalopathies (TSEs, of which BSE was one form), had adopted a Decision (97/534) regarding the use of "special risk materials" (SRMs). This could have affected all uses of bovine materials, including those used in medicinal products.
After two years of debate this Decision had yet to be implemented; the latest proposed date for implementation was January, 2000. In the meantime guidelines on the use of materials of animal origin in medicinal products produced in 1991 by the Committee for Proprietary Medicinal Products (CPMP) had been revised and the revision adopted in April, 1999. Medicines legislation had now been amended to give legal force to the use of the CPMP guidelines and the 1997 decision would be amended to remove medicinal products from its scope. With regard to the implementation of the modified medicines legislation, the Commission’s first thinking on application of the guidelines seemed to envisage some form of certification system for the materials involved. The debate on implementation would continue.
Finally, turning to the subject of batch release, Mr Murray said that although there were no formal proposals on this subject yet, it had been discussed at a meeting of the European Medicines Inspectors Group in December, 1998, and consultation was expected later this year. Among issues to be covered were the definition of batch for importation, and the responsibility for release of such batches in various circumstance onto the European market by the qualified person. Which qualified person was responsible for the release of the final product? This was another interesting ongoing debate, he said.
Although mutual recognition agreements (MRAs) on good manufacturing practice (GMP) inspection will offer benefits to patients, there should be a simpler approach to MRAs between the United States and the European Union, and more dialogue with the pharmaceutical industry, Mr David Begg (David Begg Associates) said.
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David Begg: promoting harmonisation |
The general basis of mutual recognition was about removing barriers to trade, promoting harmonisation (both of GMP standards and guidelines, and the application of GMP inspection in industry), fostering good relations between the pharmaceutical industry and regulatory authorities, sharing information and - most important - protecting patients. However, Mr Begg had some personal comments on MRAs. One was that the European Union and the United States still could not agree a definition of GMP. The EU definition was the simpler but the US would not agree to it. Another was that the principle of equivalence should be applied to individual states within the United States, as well as to the US and EU. There was also the problem of inconsistency of GMP inspections. This probably existed not only between inspectors within the UK but also between European countries, and this would take some time to sort out.
There were also the questions of how much MRA agreements would cost, whether the timescales would be met, whether joint inspection would work in practice and whether the UK patient would be better protected.