The 14th Amendment of the German Drug Act came into force on 6 September 2005 making Germany the first EU member state to transpose the revised EU Pharmaceutical Legislation1 into national law. This article provides an overview of the contents and highlights some of its key provisions.
2. IMPLEMENTATION IN GERMANY
Altogether the 14th Amendment reflects an almost one-to-one implementation of the revised EU Pharmaceutical Legislation. An exception constitutes the "compassionate use", the renewals of marketing authorisations and the "sunset clause". The German legislator used the flexibility offered by the EU Pharma Legislation in this regard. The implications of the 14th Amendment are not limited to the German Drug Act (Arzneimittelgesetz – "AMG"). The Drug Advertising Act (Heilmittelwerbegesetz – "HWG"), the Patent Act (Patentgesetz – "PatG") and the Hospitals’ Fees Act (Krankenhausentgeltgesetz – "KEntgG") as well as the National Ordinance on Hospital Rates (Bundespflegesatzverordnung – "BPflV") have also been affected.
2.1 German Drug Act
Several key changes to the AMG are:
- Ready Prepared Medicinal Products
- Pharmaceutical Entrepreneur
- Qualified person
- Marketing authorisation
- Labelling, patient information and summary of product characteristics
- Periodic safety update reports
- Dossier protection
According to Sec. 4 para. 1 of the AMG the definition of ready prepared medicinal products ("Fertigarzneimittel") includes products to be placed on the market which are manufactured and packaged in advance. This has been extended by the 14th Amendment. Products manufactured in any other way not necessarily "in advance" are also included. The extension of the scope of Sec. 4 para. 1 AMG affects the necessity of a marketing authorisation. A marketing authorisation is in principle necessary with respect to every industrial or commercial manufacturing of a medicinal product. However, products manufactured in pharmacies and unfinished products to be further processed by a manufacturer are excluded from the scope of Sec. 4 para.1 AMG.
Prior to the 14th Amendment, Sec. 4 para. 18 AMG stipulated that a pharmaceutical entrepreneur was any person placing medicinal products under his own name onto the market. Sec. 4 para. 18 AMG now clarifies that holders of a marketing authorisation or a registration are also pharmaceutical entrepreneurs. As to co-marketing ("Mitvertrieb") the amendment of Sec. 4 para. 18 AMG does not affect the legal position.
The definition of "manufacturing" has been extended. Following the 14th Amendment to Sec. 4 para. 14 AMG, release of the product now constitutes a part of the manufacturing process. "Product release" is defined as supervision of a batch having been produced and checked according to the applicable regulations and in the case of authorised medicinal products also according to the requirements of the marketing authorisation. The product release requires a manufacturing licence according to Sec. 13 AMG. If subcontractors (for example, contract manufacturers) perform product releases they have to apply for a manufacturing licence. As the holder of a manufacturing licence the subcontractor can also be subject to product liability laws.
Prior to the 14th Amendment a manufacturing licence applicant had to appoint a head of quality control and a head of production. Following the amendments to Sec. 14-15 AMG, the applicant of a manufacturing licence has to appoint a qualified person. The person appointed as a qualified person must either have a licence to practise pharmacy or hold a university degree in pharmacy, chemistry, biology or human or veterinary medicine. The person shall also have at least two years practical quality control experience. In addition, the manufacturing licence applicant has to appoint a head of production and a head of control. The appointed persons have to be duly qualified and experienced. The qualified person can be either head of production or head of quality control but not both. The only exception applies to the production of medicated feed.
According to Sec. 31 para. 1a AMG, marketing authorisations already renewed as of 1 January 2001 are valid for an unlimited period. However, the competent authorities are entitled to limit the renewal period to five years on the basis of any negative pharmacovigilance concerns regarding the safe placement of the medicinal product onto the market.
Pursuant to Sec. 31 para. 1 no. 1 AMG (the "sunset clause") a marketing authorisation expires if a medicinal product is not placed onto the market within three years after issue of the marketing authorisation. The same applies to a medicinal product that has been off the market for three years. If the active ingredients of medicinal products have been placed onto the market within the European Union for at least ten years, no pharmaceutical and toxicological documentation is required for the application relating to marketing authorisations ("well established use"; Sec. 22 para. 3 no. 1 AMG).
Before the 14th Amendment came into force patients could only be treated with non-authorised medicinal products in an emergency. Pursuant to Sec. 21 para. 2 no. 6 AMG it is now permissible to provide medicinal products to a patient if a marketing authorisation application is pending under the centralised authorisation procedure, provided the patient is suffering from a life threatening illness or an illness causing serious disability and he cannot be sufficiently treated with an authorised medicinal product. In addition it is possible to provide medicinal products to patients if the products are being tested in clinical trials and there is sufficient evidence of their efficacy and safety ("compassionate use").
The German law (Sec. 10–11 AMG) directly adopted the European Directives regarding labelling, patient information and summary of product characteristics. Thus the legal content and formal requirements have been harmonised with European law. The transitional period in this regard will end on 1 January 2009.
Pursuant to Sec. 63b para. 5 AMG the frequency for filing periodic safety update reports (PSURs) has been reduced from five to three years. During the period between the issue of the marketing authorisation and the placement onto the market the pharmaceutical entrepreneur has to file PSURs every six months. The same applies to the first two years after placement onto the market.
In relation to authorisation for generics, the dossier protection for the reference medicinal product has been reduced to eight years. If an application for a marketing authorisation is filed in the eight year dossier protection period the authorities are not allowed to refer to the dossiers of the reference medicinal product. Two additional years of market exclusivity are also granted and the exclusive marketing period can be extended for another year, if within the eight years of the dossier protection period the marketing authorisation is broadened to further indications and the extension of indications shows a significant therapeutic benefit. The new protection periods ("8+2+1") apply only to those products that are authorised after 30 October 2005.
The definition of generics according to a judgement of the European Court of Justice2 is now statutorily implemented in the AMG. Pursuant to Sec. 24b para. 2 AMG a generic has to consist of the same compound, the same pharmaceutical form and the same biological equivalence.
3. GERMAN PATENT ACT – ROCHE BOLAR EXEMPTION
Pursuant to Sec. 11 no. 2b PatG patent protection does not extend to studies and trials and the consequential practical requirements that are obligatory in order to receive European marketing authorisation. According to the wording of Sec. 11 no. 2b PatG the "Bolar" exemption allows both generic testing as well as further research.
4. DRUG ADVERTISING ACT
Furthermore, provisions of the HWG have been amended. The revisions only apply to advertising to the general public. The scope of the HWG and its restrictions have been extended to commercial statements regarding cosmetic surgery without medical indication. Additionally, according to Sec. 4a para. 2 HWG, it is not possible to advertise by making claims to consumers that a certain product is reimbursable by public sick funds.
5. HOSPITALS’ FEES ACT AND NATIONAL ORDINANCE ON HOSPITAL RATES
The German Federal Social Court held in a well publicised judgement that German sick funds are not obliged to cover the costs of basic care of hospitalised patients that are participating in clinical trials with unapproved investigational products. The pharmaceutical entrepreneur who sponsors the clinical trial would have to bear these costs. The judgement has been criticised as unbalanced and inappropriate. The legislator has revised this judgment with the 14th Amendment. Now German sick funds have to cover the costs for basic care for all patients that are hospitalised for reasons other than a clinical trial (Sec. 8 KEntgG, Sec. 10 BPflV). The pharmaceutical entrepreneur is obliged only to pay for the additional costs related to the clinical trial such as investigational medicinal products, additional analysis or any prolonged stay in hospital.
1 Directive 2004/27/EC on the Community Code relating to medicinal products for human use; Directive 2004/28/EC on the Community Code relating to medicinal products for animal use; Directive 2004/24/EC on traditional herbal medicinal products; Directive 2004/23/EC on setting standards of quality and safety for the donation procurement, testing, processing, preservation, storage and distribution of human tissues and cells; Regulation EC/726/2004 on Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency.
2 Generics Ltd. – Official Journal of the European Union C 368/96.
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