European Commission proposes new draft on IMPs

International law firm Hogan & Hartson examines the key provisions of the proposed legislation

On 1 July 2004, the European Commission published a draft Directive aimed at laying down principles and detailed guidelines for good clinical practice as regards investigational medicinal products (IMPs) for human use, as well as requirements for authorisation of manufacturing or importation of such products.The draft Directive aims to extend certain basic provisions of the European Clinical

Trials Directive (Directive 2001/20/EC)1 to IMPs for human use. These basic provisions concern:

1. the principles of good clinical practice;

2. the requirements for the authorisation of the manufacture or importation of such products; and

3. the guidelines on the documentation relating to clinical trials, archiving, qualification of inspectors and inspections procedures.

The draft Directive aims at protecting trial subjects against the possibility that unnecessary clinical trials are conducted involving the use of IMPs. Additionally, it aims to ensure that the professionals involved apply the same standards of good clinical practice at all stages of the organisation of an IMP clinical trial.

Should the draft Directive be adopted in its current format, sponsors, investigators and other participants would have to take into account the scientific guidelines concerning quality, safety and efficacy of medicinal products for human use as agreed by the Committee for Medicinal Products for Human Use (CHMP) and published by the EMEA (the European Medicines Agency), as well as the other pharmaceutical Community guidelines published by the European Commission in the different volumes of the rules governing medicinal products in the European Community.

sponsors

Sponsors would be able to delegate their functions to an individual, a company, an institution or an organisation, but would have to remain responsible for ensuring that the conduct of IMP trials and the final data generated comply with the requirements of the EU Clinical Trials Directive.

ethics committees

The draft seeks to harmonise EU member state rules on the functioning of the ethics committees in the event of IMP trials. Ethics Committees would have to adopt rules of procedures to implement the requirements introduced by the European Clinical Trials Directive concerning the functioning of the Ethics Committees. Ethics Committees would have to retain documents relating to a clinical trial for at least three years.

manufacturing or import authorisation

The manufacture or import of an IMP would be subject to thorough authorisation. Authorisation would be required notwithstanding that the products manufactured are intended for exports. Authorisation would also be required for imports from third countries into a Member State. The competent authority would be entitled to suspend or revoke the authorisation if the holder of the authorisation fails, at any time, to comply with the relevant requirements. The applicant would have to meet (and provide proof of meeting) a list of mandatory requirements, which are introduced by the draft Directive. These relate to a specification of the medicinal product and pharmaceutical forms, the relevant manufacture or import operations, and the manufacturing process (where necessary). Furthermore, a so-called 'qualified person' must be provided for.

key elements of the Trial Master File

The Trial Master File in respect of an IMP consists of essential documents that enable the evaluation of the conduct of a clinical trial and the quality of the data produced. The draft Directive provides that the sponsor and the investigator have to retain essential documents for five years after the completion of the trial. It would be required that the documents be archived in a coherent way, which would ensure their prompt availability, in case of request on the part of public authorities. Any transfer of ownership of the data or of the documents would have to be documented.

qualification of inspectors and

inspection procedures

Guidelines on minimum standards should exist as regards the qualification, education and training of IMP clinical trials inspectors. Member States would be made responsible for ensuring that inspectors have completed adequate university education, that their training is appropriate, and that their knowledge includes the provisions of applicable EU law, national legislation and guidelines applicable to the conduct of clinical trials and the granting of marketing authorisation.

The draft Directive states that Good Clinical Trials Inspections may take place at any time (before, during and after the conduct of clinical trials). Inspections may be requested and coordinated by the European Medicine Agency (EMEA). Member States would be requested to:

1. define the access to the clinical trials sites and relevant data on the part of the inspectors and of the competent authority;

2. establish procedures for verification of good clinical practice compliance;

3. lay down rules to ensure confidentiality by inspectors and other experts; and

4. keep a database of the inspectors, their qualification, training and experience.

The Draft Directive is currently being examined and final adoption is not expected before the end of 2004. Member States would be expected to transpose the text of the Directive into national legislation within six months after the entry into force of the Directive, which would be 20 days following publication in the Official Journal of the European Communities, probably sometime during 2005.