Member States shall take the measures necessary to ensure that the procedure described in this Article is followed for commencement of a clinical trial.

The sponsor may not start a clinical trial until the Ethics Committee has issued a favourable opinion and inasmuch as the competent authority of the Member State concerned has not informed the sponsor of any grounds for non-acceptance. The procedures to reach these decisions can be run in parallel or not, depending on the sponsor.

Before commencing any clinical trial, the sponsor shall be required to submit a valid request for authorisation to the competent authority of the Member State in which the sponsor plans to conduct the clinical trial.

If the competent authority of the Member State notifies the sponsor of grounds for non-acceptance, the sponsor may, on one occasion only, amend the content of the request referred to in paragraph 2 in order to take due account of the grounds given. If the sponsor fails to amend the request accordingly, the request shall be considered rejected and the clinical trial may not commence.

Consideration of a valid request for authorisation by the competent authority as stated in paragraph 2 shall be carried out as rapidly as possible and may not exceed 60 days. The Member States may lay down a shorter period than 60 days within their area of responsibility if that is in compliance with current practice. The competent authority can nevertheless notify the sponsor before the end of this period that it has no grounds for non-acceptance.

No further extensions to the period referred to in the first subparagraph shall be permissible except in the case of trials involving the medicinal products listed in paragraph 6, for which an extension of a maximum of 30 days shall be permitted. For these products, this 90-day period may be extended by a further 90 days in the event of consultation of a group or a committee in accordance with the regulations and procedures of the Member States concerned. In the case of xenogenic cell therapy there shall be no time limit to the authorisation period.

Without prejudice to paragraph 6, written authorisation may be required before the commencement of clinical trials for such trials on medicinal products which do not have a marketing authorisation within the meaning of Directive 65/65/EEC and are referred to in Part A of the Annex to Regulation (EEC) No 2309/93, and other medicinal products with special characteristics, such as medicinal products the active ingredient or active ingredients of which is or are a biological product or biological products of human or animal origin, or contains biological components of human or animal origin, or the manufacturing of which requires such components.

Written authorisation shall be required before commencing clinical trials involving medicinal products for gene therapy, somatic cell therapy including xenogenic cell therapy and all medicinal products containing genetically modified organisms. No gene therapy trials may be carried out which result in modifications to the subject's germ line genetic identity.