Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use (c. 83)

[F1 ANNEX I U.K. ANALYTICAL, PHARMACOTOXICOLOGICAL AND CLINICAL STANDARDS AND PROTOCOLS IN RESPECT OF THE TESTING OF MEDICINAL PRODUCTS

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).

[F2 PART IV U.K. ADVANCED THERAPY MEDICINAL PRODUCTS

3. SPECIFIC REQUIREMENTS REGARDING MODULE 3 U.K.

3.2. Specific requirements for gene therapy medicinal products U.K.

3.2.1. Introduction: finished product, active substance and starting materials U.K.

3.2.1.1. Gene therapy medicinal product containing recombinant nucleic acid sequence(s) or genetically modified microorganism(s) or virus(es) U.K.

The finished medicinal product shall consist of nucleic acid sequence(s) or genetically modified microorganism(s) or virus(es) formulated in their final immediate container for the intended medical use. The finished medicinal product may be combined with a medical device or active implantable medical device.

The active substance shall consist of nucleic acid sequence(s) or genetically modified microorganism(s) or virus(es).

3.2.1.2. Gene therapy medicinal product containing genetically modified cells U.K.

The finished medicinal product shall consist of genetically modified cells formulated in the final immediate container for the intended medical use. The finished medicinal product may be combined with a medical device or active implantable medical device.

The active substance shall consist of cells genetically modified by one of the products described in section 3.2.1.1 above.

3.2.1.3. In the case of products consisting of viruses or viral vectors, the starting materials shall be the components from which the viral vector is obtained, i.e. the master virus vector seed or the plasmids used to transfect the packaging cells and the master cell bank of the packaging cell line. U.K.

3.2.1.4. In the case of products consisting of plasmids, non-viral vectors and genetically modified microorganism(s) other than viruses or viral vectors, the starting materials shall be the components used to generate the producing cell, i.e. the plasmid, the host bacteria and the master cell bank of recombinant microbial cells. U.K.

3.2.1.5. In the case of genetically modified cells, the starting materials shall be the components used to obtain the genetically modified cells, i.e. the starting materials to produce the vector, the vector and the human or animal cells. The principles of good manufacturing practice shall apply from the bank system used to produce the vector onwards. U.K.

3.2.2. Specific requirements U.K.

In addition to the requirements set out in sections 3.2.1 and 3.2.2 of Part I of this Annex, the following requirements shall apply:

(a)

information shall be provided on all the starting materials used for the manufacture of the active substance, including the products necessary for the genetic modification of human or animal cells and, as applicable, subsequent culture and preservation of the genetically modified cells, taking into consideration the possible absence of purification steps;

(b)

for products containing a microorganism or a virus, data on the genetic modification, sequence analysis, attenuation of virulence, tropism for specific tissues and cell types, cell cycle dependence of the microorganism or virus, pathogenicity and characteristics of the parental strain shall be provided;

(c)

process-related impurities and product-related impurities shall be described in the relevant sections of the dossier, and in particular replication competent virus contaminants if the vector is designed to be replication incompetent;

(d)

for plasmids, quantification of the different plasmid forms shall be undertaken throughout the shelf life of the product;

(e)

for genetically modified cells, the characteristics of the cells before and after the genetic modification, as well as before and after any subsequent freezing/storage procedures, shall be tested.

For genetically modified cells, in addition to the specific requirements for gene therapy medicinal products, the quality requirements for somatic cell therapy medicinal products and tissue engineered products (see section 3.3) shall apply.] ]

Textual Amendments

F2 Substituted by Commission Directive 2009/120/EC of 14 September 2009 amending Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use as regards advanced therapy medicinal products (Text with EEA relevance).