National Exemption: Authorization according to § 4b Abs. 3 AMG
Advanced therapy medicinal products (ATMPs) are subject to centralized approval by the European Medicines Agency (EMA) in accordance with Regulation (EC) No 1394/2007. In exceptional cases, ATMP manufacturers have the possibility to obtain a national approval, especially if a routine manufacturing process of the ATMP according to specific quality standards is not possible. For this purpose, the administration must take place exclusively under the professional responsibility of a physician on an individual medical prescription of a medicinal product prepared specifically for an individual patient in a specialized health care facility. The terms “specialized health care facility” are defined in § 14 (2) Abs. 2 of the Transfusion Act (Transfusionsgesetz, TFG).
In Germany, the Paul Ehrlich Institute (PEI) is responsible for the approval of non-routine ATMPs.
A medicinal product is not routinely manufactured if it is manufactured only on a small scale (= small quantity, low frequency), and deviations are made in the manufacturing process that are medically justified for an individual patient. A medicinal product is also considered to be non-routine if it has not yet been manufactured in sufficient quantities so that necessary knowledge for a comprehensive product assessment is not yet available.
For ATMP manufacturing, there must also exist a permit for obtaining the starting material from the donor and the laboratory tests required for obtaining it in accordance with § 20b of the German Medicines Act (Arzneimittelgesetz, AMG) (if human tissues and cells are used as starting material) as well as the manufacturing authorization in accordance with § 13 AMG.
In most cases, the approval is granted for a limited period of time and is determined by the PEI in each individual case. Whether the requirements of the exemption regulation continue to be met is reviewed regularly (intervals are determined by the PEI). The holder of the authorization must therefore submit documents to the PEI at certain intervals on the scope of manufacture and on knowledge gained for the comprehensive assessment of the medicinal product.
The revocation of the authorization occurs when routine use is reached. If possible, the ATMP manufacturer (authorization holder) should prepare a clinical trial until the revocation of the authorization (when knowledge is reached), which can be followed by the central authorization at the EMA.
The national exemption is intended to take into account the rapid progress of science and technology in the field of ATMPs.
We will gladly support you in applying for or extending an exemption according to § 4b Abs. 3 AMG as well as in all measures to obtain the manufacturer's authorization!