Directive 2001/83/EC of the European Parliament and of the CouncilDangos y teitl llawn

[F1 1.1. Plasma-derived medicinal product U.K.

For medicinal products derived from human blood or plasma and by derogation from the provisions of Module 3, the dossier requirements mentioned in ‘ Information related to the starting and raw materials ’ , for starting materials made of human blood/plasma may be replaced by a Plasma Master File certified in accordance with this Part.

a) Principles U.K.

For the purposes of this Annex:

• Plasma Master File shall mean a stand-alone documentation, which is separate from the dossier for marketing authorisation which provides all relevant detailed information on the characteristics of the entire human plasma used as a starting material and/or a raw material for the manufacture of sub/intermediate fractions, constituents of the excipient and active substance(s), which are part of medicinal products or medical devices referred to in Directive 2000/70/EC of the European Parliament and of the Council of 16 November 2000 amending Council Directive 93/42/EC as regards medical devices incorporating stable derivatives of human blood or human plasma (1) .

• Every centre or establishment for fractionation/processing of human plasma shall prepare and keep updated the set of detailed relevant information referred to in the Plasma Master File.

• The Plasma Master File shall be submitted to the Agency or to the competent authority by the applicant for a marketing authorisation or the holder of the marketing authorisation. Where the applicant for a marketing authorisation or the marketing authorisation holder differs from the holder of the Plasma Master File, the Plasma Master File shall be made available to the applicant or marketing authorisation holder for submission to the competent authority. In any case, the applicant or marketing authorisation holder shall take responsibility for the medicinal product.

• The competent authority that is evaluating the marketing authorisation shall await for the Agency to issue the certificate before deciding on the application.

• Any marketing authorisation dossier containing a human plasma-derived constituent shall refer to the Plasma Master File corresponding to the plasma used as a starting/raw material.

b) Content U.K.

In accordance with the provisions of Article 109, as amended by Directive 2002/98/EC, which refers to the requirements for donors and the testing of donations, the Plasma Master File shall include information on the plasma used as starting/raw material, in particular:

(1)

Plasma origin

(i)

information on centres or establishments in which blood/plasma collection is carried out, including inspection and approval, and epidemiological data on blood transmissible infections.

(ii)

information on centres or establishments in which testing of donations and plasma pools is carried out, including inspection and approval status.

(iii)

selection/exclusion criteria for blood/plasma donors.

(iv)

system in place which enables the path taken by each donation to be traced from the blood/plasma collection establishment through to finished products and vice versa.

(2)

Plasma quality and safety

(i)

compliance with European Pharmacopoeia Monographs.

(ii)

testing of blood/plasma donations and pools for infectious agents, including information on test methods and, in the case of plasma pools, validation data on the tests used.

(iii)

technical characteristics of bags for blood and plasma collection, including information on anticoagulants solutions used.

(iv)

conditions of storage and transport of plasma.

(v)

procedures for any inventory hold and/or quarantine period.

(vi)

characterisation of the plasma pool.

(3)

System in place between the plasma-derived medicinal product manufacturer and/or plasma fractionator/processor on the one hand, and blood/plasma collection and testing centres or establishments on the other hand, which defines the conditions of their interaction and their agreed specifications.

In addition, the Plasma Master File shall provide a list of the medicinal products for which the Plasma Master File is valid, whether the medicinal products have been granted a marketing authorisation or are in the process of being granted such an authorisation, including medicinal products referred to in Article 2 of Directive 2001/20/EC of the European Parliament and of the Council relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use.

c) Evaluation and Certification U.K.

• For medicinal products not yet authorised, the marketing authorisation applicant shall submit a full dossier to a competent authority, which shall be accompanied by a separate Plasma Master File where one does not already exist.

• The Plasma Master File is subject to a scientific and technical evaluation carried out by the Agency. A positive evaluation shall result in a certificate of compliance with Community legislation for the Plasma Master File, which shall be accompanied by the evaluation report. The certificate issued shall apply throughout the Community.

• The Plasma Master File shall be updated and re-certified on an annual basis.

• Changes subsequently introduced to the terms of a Plasma Master File must follow evaluation procedure laid down by Commission Regulation (EC) No 542/95 (2) concerning the examination of variations to the terms of a marketing authorisation falling within the scope of Council regulation (EEC) No 2309/93 of 22 July 1993 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Agency for the Evaluation of Medicinal Products (3) . Conditions for the assessment of these changes are laid down by Regulation (EC) No 1085/2003.

• As a second step to the provisions in the first, second, third and fourth indents, the competent authority that will grant or has granted the marketing authorisation shall take into account the certification, re-certification or variation of the Plasma Master File on the concerned medicinal product(s).

• By derogation from the provisions of the second indent of the present point (evaluation and certification), where a Plasma Master File corresponds only to blood/plasma-derived medicinal products the marketing authorisation of which is restricted to a single Member State, the scientific and technical evaluation of the said Plasma Master File shall be carried out by the national competent authority of that Member State.]

Textual Amendments

F1 Substituted by Commission directive 2003/63/EC of 25 June 2003 amending Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use (Text with EEA relevance).

(1)

[F1 OJ L 313, 13.12.2000, p. 22 .]

(2)

[F1 OJ L 55, 11.3.1995, p. 15 .]

(3)

[F1 OJ L 214, 24.8.1993, p. 1 .]

Textual Amendments

F1 Substituted by Commission directive 2003/63/EC of 25 June 2003 amending Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use (Text with EEA relevance).