Licensing Guidelines and Regulations

Enfoque por país/Germany | Posted 30/09/2013 post-comment0 Post your comment

First posted: 30 September 2013 

The German healthcare system is characterised by a predominance of mandatory Social Health Insurance (SHI) with multiple competing sickness funds and a private/public mix of providers (Bismarck model). In 2005, about 85.4% of the population were covered by comprehensive SHI. This is complemented by three co-existing schemes: private health insurance and two specific governmental schemes for civil servants [1].

Drug products may be placed on the market in Germany after approval by the competent federal authority under § 21 paragraph 1 of the German Medicines Act (Arzneimittelgesetz, AMG) or registered under § 38 section 1 and § 39a of the AMG [2].

Approval of medicines for human use is the responsibility of the independent Federal Institute for Pharmaceuticals and Medical Devices (Bundesintitut für Arzneimittel und Medizinprodukte, BfArM), which is under the portfolio of the Federal Ministry of Health. For sera, vaccines, test allergens, test sera and test antigens, and blood preparations, the Paul Ehrlich Institute (PEI) in Langen is the competent authority. Veterinary drugs are the responsibility of the Federal Office of Consumer Protection and Food Safety in Bonn [2].

One of the main tasks of the BfArM is the authorisation of finished medicinal products on the basis of the AMG. In the course of these licensing procedures it reviews the proof of efficacy, safety, and adequate pharmaceutical quality of the finished medicinal products [3].

For generic drugs BfArM checks for, amongst others, whether the pharmaceutical quality, efficacy and safety of both the original and the generic drug product are comparable [4].

Approvals are limited to five years. Extensions are granted upon request and after further review. Modifications and major changes in manufacturing procedures of drugs already approved must also have BfArM/PEI approval [2].

In the case of a generic medicinal product an application can be made, with reference to the previous applicant’s medicinal product (reference medicinal product), provided that the reference medicinal product has been authorised for at least eight years. This also applies to authorisation in another member state or the EU [5].

A generic medicinal product may, however, not be placed on the market until ten years have elapsed following the first authorisation of the reference medicinal product. This period may be extended to a maximum of eleven years in the case of new therapeutic indications of significant clinical benefit in comparison with existing therapies [5].

Authorisation as a generic medicinal product requires that the medicinal product in question has the same qualitative and quantitative composition of active substances and the same pharmaceutical form as the reference medicinal product and that the bioequivalence has been demonstrated in bioavailability studies [5].

Different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance are considered to be one and the same active substance unless their properties differ significantly with regard to safety or efficacy. In such cases, the applicant must submit additional proof of the safety or efficacy of the different salts, esters, ethers, isomers, mixture of isomers, complexes or derivatives of the active substance. This also applies to the various immediate release oral pharmaceutical forms [5].

The applicant is not required to submit bioavailability studies if he/she can otherwise demonstrate that the generic medicinal product meets the relevant bioequivalence criteria in accordance with current scientific knowledge [5].

In cases where the medicinal product does not meet the requirements of a generic medicinal product or where the bioequivalence cannot be demonstrated through bioequivalence studies or in the case of a change in the active substance, therapeutic indication, strength, pharmaceutical form or route of administration vis-à-vis the reference medicinal product, the results of appropriate preclinical tests or clinical trials must be provided [5].

Where a biological medicinal product which is similar to a biological reference medicinal product does not meet the conditions for generic medicinal products, owing to, in particular, differences relating to raw materials or differences between the manufacturing processes of the biological medicinal product and the reference biological medicinal product, the results of appropriate preclinical tests or clinical trials relating to these deviations must be provided [5].

References

1.  European Commission. Pharmaceutical Pricing and Reimbursement Information project: Germany. May 2008.

2.  Bundesintitut für Arzneimittel und Medizinprodukte (BfArM). Medicines [monograph on the Internet]. BfArM [cited 2013 Sep 30]. German. Available from: www.bfarm.de/cln_103/DE/Arzneimittel/arzneimittel-startseite.html?nn=1010882

3.  Bundesintitut für Arzneimittel und Medizinprodukte (BfArM). About us [monograph on the Internet]. BfArM [cited 2013 Sep 30]. German. Available from: www.bfarm.de/cln_094/EN/BfArM/bfarm-node-en.html

4.  [Generikum] [monograph on the Internet]. Progenerika [cited 2013 Sep 30]. German. Available from: www.progenerika.de/de/generika.html

5.  Medicinal Products Act (Arzneimittelgesetz – AMG) [The Drug Law] of the Federal Republic of Germany Non-official translation [monograph on the Internet]. BfArM [cited 2013 Sep 30]. German. Available from: www.bfarm.de/SharedDocs/1_Downloads/EN/BfArM/service/AMG_en.pdf?__blob=publicationFile

Useful information sources

EMA, Committee for Proprietary Medicinal Products (CPMP), Guideline on the investigation of bioequivalence (CPMP/EWP/QWP/1401/98 Rev.1) [monograph on the Internet]. London, UK, EMA; 2008 Jul 24 [cited 2013 Sep 30]. Available from: www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003011.pdf

EMA, Committee for Medicinal Products for Human Use (CHMP), EMEA Procedural Advice for Users of the Centralised Procedure for Generic/Hybrid Applications (EMEA/CHMP/ 225411/2006) [monograph on the Internet]. London, UK, EMA; 2008 Jul 2 [cited 2013 Sep 30]. Available from: www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004018.pdf

EMA, Committee for Proprietary Medicinal Products (CPMP), Note for guidance on modified release oral and trans-dermal dosage forms: Section II (pharmacokinetic and clinical evaluation) (CPMP/EWP/280/96) [monograph on the Internet]. London, UK, EMA; 1999 [cited 2013 Sep 30]. Available from: www.ema.europa.eu/pdfs/human/ewp/028096en.pdf

EMA, Committee for Proprietary Medicinal Products (CPMP), Note for guidance on the clinical requirements for locally applied, locally acting products containing known constituents (CPMP/EWP/239/95) [monograph on the Internet]. London, UK, EMA; 1995 [cited 2013 Sep 30]. Available from: www.ema.europa.eu/pdfs/human/ewp/023995en.pdf

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