Germany regulatory affairs

  • View

  • Download

Embed Size (px)


Germany regulatory affairs AAPS

Text of Germany regulatory affairs

  • 1. PRAAAPS2014Ibrahim Mahamoud

2. Regulatory overview Medicinal products are mainly regulated by the DrugAct (Arzneimittelgesetz) and the Facility Ordinance forActive Ingredients of Pharmaceuticals (Arzneimittel-undWirkstoffherstellungsverordnung). These address, for example, manufacturing,marketing, distributing and pharmacovigilance. Rulesfor advertising medicinal products are set out in theHealthcare Advertising Act (Heilmittelwerbegesetz). 3. Medicinal products for human use are subject toa marketing authorisation from :the Federal Institute for Drugs and Medical Devices(Bundesinstitut fr Arzneimittel und Medizinprodukte)(BfArM)the Federal Agency for Sera and Vaccines (Paul-Ehrlich-Institut) (PEI), if not covered by the Europeancentralised procedure. 4. Overview Pricing and state funding Manufacturing Clinical trials Marketing Advertising Packaging and labelling Traditional herbal medicines Patents Trade marks The regulatory authorities 5. Pricing and state funding The funding of public health insurance: A fixed contribution rate was introduced atfederal level. Every public health insurance fund will receive a lump sum for each insuredperson and an additional sum depending on the age and risk-level of the insured person.If the lump sum does not cover the insurer's costs, the public health insurance fund canimpose additional contributions on each insured person with a maximum of 1% of theincome liable to insurance deductions. Public health insurance funds provide benefits (generally benefits in kind) and services.Therefore, the insured person does not have to pay for the services directly. Federal lawlargely covers the range of benefits offered by public health insurers. About 85% of theGerman population are covered by public health insurance. Insured persons canchoose optional rates covering, for example, special forms of medical care, non-reimbursablepharmaceuticals, and so on. Private insurance companies practise a cost-reimbursement principle where the insuredperson pays the medical bills and is reimbursed by the insurance company afterwards. 6. Pricing ,,,,,,,,,,, the pricing of drugs by manufacturers and dealers is still largelyunregulated, the Ordinance on Pharmaceutical Product Pricing(Arzneimittelpreisverordnung) sets permissible margins for wholesalers andpharmacists. The Ordinance applies only to prescription medicinal products. The Fifth Social Security Code (Sozialgesetzbuch V) sets compulsory discountsfor public health insurance funds and pharmacies (section 130, 130a, Fifth SocialSecurity Code). Retail prices for prescription drugs must be uniform across all pharmacies. The Act on the Improvement of Economic Efficiency for the Provision ofMedicinal Products (Gesetz zur Verbesserung derWirtschaftlichkeit derArzneimittelversorgung) introduced further compulsory discounts for publichealth insurers. 7. In general, prescription medicinal products are reimbursed by public healthinsurance funds. The patients obtain a prescription from their physician andcollect the medicinal product from the pharmacy. The reimbursement ofmedicinal products is then paid directly to the pharmacist by the public healthinsurance funds. The Ordinance on Pharmaceutical Product Pricing providesthe relevant financial framework for prescription drugs that must be sold inpharmacies. The regulation allows the pharmacy or wholesalers to add ona fixed percentage charge to the freely calculated manufacturer's price,when selling the drug to final consumers or pharmacies respectively.About 65% of prescriptions are affected by this regulation. The cost of medicinal products that are not "necessary and economic" or whichare prescribed in cases of specific minor impairments of health is notreimbursed at all. Specific medicinal products, which are considered inefficientor which cannot provide the necessary proof of sufficient therapeutic benefits,are set out in a government "negative list". Generally, over-the-counter (OTC) products are not refundable. 8. Manufacturing 9. Manufacturing - Application Authorisation is required for each production facilitylocated in Germany. The competent authority is determined by the statesand is usually the general regional governmentauthority (Regierungsprsidium) or the local orregional public health authority (Gesundheitsamt). 10. Manufacturing ,,,Conditions The manufacturer must meet certain requirements setout in the Facility Ordinance for Active Ingredients ofPharmaceuticals, relating to, for example, qualitymanagement, personnel, hygiene requirements,manufacturing processes and storage. The Facility Ordinance for Active Ingredients ofPharmaceuticals complies with Directive 2003/94/ECon good manufacturing practice for medicinalproducts. ,,,, GMP 11. Restrictions on foreign applicants ,,,Manufacturing The legal requirements are equally binding on foreignand domestic manufacturers. 12. Key stages and timing ,, Manufacturing The authorisation application must be filed before themanufacturing process is started. In most cases, the publicauthority inspects the premises before delivering amanufacturing authorisation. The application must be accompanied by several documents.The public authority only issues the authorisation if it is surethat the necessary safety and quality benchmarks arecomplied with. The competent authority must decide on an application fora manufacturing authorisation within three months(section 17 paragraph 1, Drug Act). However, if the authority asksthe applicant to remedy defects in the application, this time limitis interrupted (section 17 paragraph 3, Drug Act). 13. Manufacturing Fee The competent authorities must fix fees on a case-by-casebasis. Their decisions are made according to a legalframework that can vary between federal states. 14. Period of authorization and renewals,,,Manufacturing Usually, the competent authorities give an unlimitedaccreditation. 15. What powers does the regulator have to:Manufacturing Monitor compliance with manufacturing authorizations? Impose penalties for a breach of a manufacturing authorization? The competent authorities , can monitor a manufacturer'scompliance with its manufacturing authorisation. They canenforce compliance using the Drug Act (section 64, DrugAct).The public officers in charge of monitoring can, for example: Enter and inspect office premises and operating rooms. Review documents on the manufacture of the products. Demand all necessary information on the company's operations. Demand samples, if the authority considers this necessary formonitoring. 16. ,,, Manufacturing Generally, premises inspections take place every twoyears. they can suspend or withdraw the marketingauthorisation (section 18, Drug Act). They can alsostop the manufacturing or seize and withdrawmedicinal products from the market (section 69, DrugAct). However, they cannot impose fines or criminalpenalties 17. Clinical trials 18. Legislation, regulatory authorities and authorizations(clinical trials) The conduct of clinical trials is regulated in the Drug Act(section 40 pp). the Ordinance on Good Clinical Practices (GCP-Verordnung)sets out details regarding the conduct of a clinical trial. Before starting a clinical trial, a trial protocol and other detailsset out in the GCP-Verordnung must be submitted for parallelapproval by the independent Ethics Committee and either theBfArM* or the **PEI (depending on the test product). The trial can begin only if both voting bodies approve (section 40paragraph 1, Drug Act). The competent authority of the relevantfederal state must be notified of the clinical trials. * Federal Institute for Drugs and Medical Devices ** Federal Agency for Sera and Vaccines 19. Consent from trial subjects,,, clinicaltrials Before including a trial subject in a clinical trial, thetrial subject must give its informed consent inwriting. Before the consent can be obtained, thephysician must explain the nature, intent, risks andimportance of the clinical trial to the trial subject. The trial subject must also give its consent to thepurpose and extent of collection and use of personaldata in the clinical trial. 20. Other conditions ,,, clinical trials The sponsor of the clinical trial must have its seat in the EUor EEA, or have a legal representative in the EU or EEA.*(European Economic Area) The clinical trial must have a superior audit managerwho must be an approbated physician with a minimum oftwo years experience in clinical trials. Patients participating in a trial must have specificinsurance cover appropriate to the risks involved, whichpays at least EUR500,000 (about US$737,000) for death orpermanent inability to work. 21. Procedural requirements ,,, clinical trials All clinical trials must be conducted according to theGood Clinical PractiGCPce () standard (section 40,Drug Act implementing Directive (EC) No. 20/2001 onthe conduct of clinical trials). In addition, products tobe tested must have a Good Manufacturing Practice(GMP) certificate. Reporting and documenting the clinical trial by thesponsor and physicians are regulated in the GCP-Verordnung(section 12 pp). 22. Marketing 23. MarketingApplication Authorizations are granted by the BfArM* or PEI**,depending on the product.Conditions Finished medicinal products can only be placed on themarket after authorisation (for pharmaceutical products)or registration (for homeopathic products). To be grantedauthorisation, pharmaceutical companies must provideproof of the pharmaceutical quality, efficacy and safety ofthe product. * Federal Institute for Drugs and Medical Devices ** Federal Agency for Sera and Vaccines 24. Marketing Key stages and timing The BfArM* accepts documentation submitted in electronic form, including CD-ROM(see Ordinance on Submission of Application - Verordnung ber die Einreichung vonUnterlagen in Verfahren fr die Zulassung und Verlngerung der Zulassung vonArzneimitteln). It usually takes two and a half years to obtain a decis