Pharma companies facing 'EU timebomb'

The new EU Clinical Trial Directive is to be implemented in all EU member states by May this year. Keren Winmill, of Penn Pharmaceutical Services, looks at the implications of the forthcoming legislation

The regulations governing clinical trial samples that are imported into EU countries will take on a new dimension from 1 May, 2004 when the new Clinical Trials Directive (2001/20/EC) is fully implemented across Europe.For many organisations that are used to running trials in Europe significant changes will need to be applied to the way in which they currently work, as the Directive covers a broad range of issues.

Patient protection, time frames for applications, the establishment of a database on clinical trials being carried out in Europe, the incorporation of GCP into European law and the manufacture, import and labelling of materials are all addressed within the legislation.

One of the most fundamental changes is the inclusion of Human Volunteer Studies, which means that even Phase I studies will now be subject to regulatory approval. The GMP Directive (91/356) has also been amended to include the requirements for investigational as well as commercial products.

Specifically there are sections on blinding of materials, manufacture in accordance with the regulatory application, training, document retention periods, validation, release, complaints and recalls of comparators, rapid unblinding and labelling. The Directive specifies that the outer packaging (or immediate packaging if no outer packaging exists) should be labelled in at least the official language of the member state.

article 13

One of the most significant elements of the Directive - Article 13 - states that companies that manufacture or import clinical trial materials into the EU must have a Manufacturing Authorisation. This must include having a Qualified Person (QP) continuously available who will be charged with ensuring that the requirements of GMP will be met.

The QP will be responsible for releasing batches of clinical materials before use in a clinical trial and the revised Annex 13 indicates that the QP must satisfy him or herself that equivalent standards of GMP (to those in the EU), apply at the manufacturer and that this should be achieved by means of participation in audit at the manufacturing site. This is usually a single visit unless processes change significantly and, in comparison with full batch-to-batch quantitative analysis, can be a very cost-effective means of releasing product.

In addition to QP release, Article 15 of the Directive provides for inspection of both investigator and manufacturing/analytical sites by the competent authorities in the Member States on a two-yearly cycle within the EU and on a 'triggered' basis outside the EU.

seeking assistance

The requirements for import licences and documentation may also change when the Clinical Trials Directive comes into force in the individual countries. At the moment it is usually the regulatory group that is in the best position to apply for the import licence, often assisted by the contractor or courier.

Some countries, such as France, currently require an import licence for each individual shipment, which can be very onerous.

For the more difficult countries, which require individual import licences, it is worth considering using a local depot. An affiliate or a contractor can advise on local operations that have suitable facilities for storage, shipment and tracking and, importantly, will comply with GMP.

The current European system can seem fragmented and the new Directive will eventually simplify the regulatory picture but companies coming into Europe can benefit greatly from seeking specialist clinical supplies services both during and after the transition.