Germany regulatory affairs AAPS

1. PRA
AAPS
2014
Ibrahim Mahamoud

2. Regulatory overview
 Medicinal products are mainly regulated by the Drug
Act (Arzneimittelgesetz) and the Facility Ordinance for
Active Ingredients of Pharmaceuticals (Arzneimittel-und
Wirkstoffherstellungsverordnung).
 These address, for example, manufacturing,
marketing, distributing and pharmacovigilance. Rules
for advertising medicinal products are set out in the
Healthcare Advertising Act (Heilmittelwerbegesetz).

3. Medicinal products for human use are subject to
a marketing authorisation from :
the Federal Institute for Drugs and Medical Devices
(Bundesinstitut für Arzneimittel und Medizinprodukte)
(BfArM)
the Federal Agency for Sera and Vaccines (Paul-
Ehrlich-Institut) (PEI), if not covered by the European
centralised 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 at
federal level. Every public health insurance fund will receive a lump sum for each insured
person 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 can
impose additional contributions on each insured person with a maximum of 1% of the
income 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 law
largely covers the range of benefits offered by public health insurers. About 85% of the
German population are covered by public health insurance. Insured persons can
choose optional rates covering, for example, special forms of medical care, non-reimbursable
pharmaceuticals, and so on.
 Private insurance companies practise a cost-reimbursement principle where the insured
person pays the medical bills and is reimbursed by the insurance company afterwards.

6. Pricing ,,,,,,,,,,,
 the pricing of drugs by manufacturers and dealers is still largely
unregulated, the Ordinance on Pharmaceutical Product Pricing
(Arzneimittelpreisverordnung) sets permissible margins for wholesalers and
pharmacists. The Ordinance applies only to prescription medicinal products.

 The Fifth Social Security Code (Sozialgesetzbuch V) sets compulsory discounts
for public health insurance funds and pharmacies (section 130, 130a, Fifth Social
Security Code).
 Retail prices for prescription drugs must be uniform across all pharmacies.
 The Act on the Improvement of Economic Efficiency for the Provision of
Medicinal Products (Gesetz zur Verbesserung derWirtschaftlichkeit der
Arzneimittelversorgung) introduced further compulsory discounts for public
health insurers.


7.  In general, prescription medicinal products are reimbursed by public health
insurance funds. The patients obtain a prescription from their physician and
collect the medicinal product from the pharmacy. The reimbursement of
medicinal products is then paid directly to the pharmacist by the public health
insurance funds. The Ordinance on Pharmaceutical Product Pricing provides
the relevant financial framework for prescription drugs that must be sold in
pharmacies. The regulation allows the pharmacy or wholesalers to add on
a 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 which
are prescribed in cases of specific minor impairments of health is not
reimbursed at all. Specific medicinal products, which are considered inefficient
or 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 facility
located in Germany.
 The competent authority is determined by the states
and is usually the general regional government
authority (Regierungspräsidium) or the local or
regional public health authority (Gesundheitsamt).

10. Manufacturing ,,,Conditions
 The manufacturer must meet certain requirements set
out in the Facility Ordinance for Active Ingredients of
Pharmaceuticals, relating to, for example, quality
management, personnel, hygiene requirements,
manufacturing processes and storage.
 The Facility Ordinance for Active Ingredients of
Pharmaceuticals complies with Directive 2003/94/EC
on good manufacturing practice for medicinal
products. ,,,, GMP

11. Restrictions on foreign applicants ,,,
Manufacturing
 The legal requirements are equally binding on foreign
and domestic manufacturers.

12. Key stages and timing ,, Manufacturing
 The authorisation application must be filed before the
manufacturing process is started. In most cases, the public
authority inspects the premises before delivering a
manufacturing authorisation.
 The application must be accompanied by several documents.
The public authority only issues the authorisation if it is sure
that the necessary safety and quality benchmarks are
complied with.

 The competent authority must decide on an application for
a manufacturing authorisation within three months
(section 17 paragraph 1, Drug Act). However, if the authority asks
the applicant to remedy defects in the application, this time limit
is interrupted (section 17 paragraph 3, Drug Act).

13. Manufacturing … Fee
 The competent authorities must fix fees on a case-by-case
basis.
 Their decisions are made according to a legal
framework that can vary between federal states.

14. Period of authorization and renewals
,,,Manufacturing
 Usually, the competent authorities give an unlimited
accreditation.

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's
compliance with its manufacturing authorisation. They can
enforce compliance using the Drug Act (section 64, Drug
Act).
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 for
monitoring.

16. ,,, Manufacturing
 Generally, premises inspections take place every two
years.
 they can suspend or withdraw the marketing
authorisation (section 18, Drug Act). They can also
stop the manufacturing or seize and withdraw
medicinal products from the market (section 69, Drug
Act).
 However, they cannot impose fines or criminal
penalties

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 details
set out in the GCP-Verordnung must be submitted for parallel
approval by the independent Ethics Committee and either the
BfArM* or the **PEI (depending on the test product).
 The trial can begin only if both voting bodies approve (section 40
paragraph 1, Drug Act). The competent authority of the relevant
federal 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,,, clinical
trials
 Before including a trial subject in a clinical trial, the
trial subject must give its informed consent in
writing. Before the consent can be obtained, the
physician must explain the nature, intent, risks and
importance of the clinical trial to the trial subject.
 The trial subject must also give its consent to the
purpose and extent of collection and use of personal
data in the clinical trial.

20. Other conditions ,,, clinical trials
 The sponsor of the clinical trial must have its seat in the EU
or EEA, or have a legal representative in the EU or EEA.*
(European Economic Area)
 The clinical trial must have a superior audit manager
who must be an approbated physician with a minimum of
two years experience in clinical trials.
 Patients participating in a trial must have specific
insurance cover appropriate to the risks involved, which
pays at least EUR500,000 (about US$737,000) for death or
permanent inability to work.

21. Procedural requirements ,,, clinical trials
 All clinical trials must be conducted according to the
Good Clinical PractiGCPce () standard (section 40,
Drug Act implementing Directive (EC) No. 20/2001 on
the conduct of clinical trials). In addition, products to
be tested must have a Good Manufacturing Practice
(GMP) certificate.
 Reporting and documenting the clinical trial by the
sponsor and physicians are regulated in the GCP-Verordnung
(section 12 pp).

22. Marketing

23. Marketing
Application
 Authorizations are granted by the BfArM* or PEI**,
depending on the product.
Conditions
 Finished medicinal products can only be placed on the
market after authorisation (for pharmaceutical products)
or registration (for homeopathic products). To be granted
authorisation, pharmaceutical companies must provide
proof of the pharmaceutical quality, efficacy and safety of
the 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 über die Einreichung von
Unterlagen in Verfahren für die Zulassung und Verlängerung der Zulassung von
Arzneimitteln).
 It usually takes two and a half years to obtain a decision. The authorities dealing with
the application can provide guidance before an application is filed. All government
authorities must provide such information and assistance as is requested (both before
and after the formal application is filed) (section 71c, Code on Administrative Procedure).
Fee
 The applicant must pay the costs of investigating the application and granting the
authorisation after the BfArM issues its decision.
 The BfArM fixes fees on a case-by-case basis according to the corresponding cost
ordinance.
 * Federal Institute for Drugs and Medical Devices

25. Period of authorisation and renewals ,,,
Marketing
 The first authorisation is usually granted for five years and can
be extended by applying to the same authority that granted it.
 (Renewal is refused if the necessary requirements of quality,
efficacy and safety are no longer fulfilled).
 After the first renewal of the authorisation, no further renewal
is needed unless the authority makes another decision, for
example, due to security reasons.
 If the application for renewal has been filed at least six months
before the end of the five-year period, the marketing of the
product can be continued until the authority issues a decision.
 The renewal fee is between EUR1,410 (about US$2,078) and
EUR4,757 (about US$7,012).

26. Advertising

27. Advertising
Legislation and regulatory authority
 Title VIII of Directive 2001/83/EC regulating the advertising of medicinal
products for human use has been implemented. There are strict regulations
on advertising campaigns that target the public. The regulations also make a
distinction between advertising activities that are limited to healthcare
professionals and those that are also addressed to potential patients.
 For medical devices, advertising provisions are less restrictive (Healthcare
Advertising Act, which applies to product-related promotional advertising).
 A company can only advertise if a responsible person or company with a seat
in the EU or EEA* has been expressly entrusted to assume the obligations
arising from the Healthcare Advertising Act (section 13, Healthcare Advertising
Act).
 *European Economic Area

28. ,,,, Advertising
 There is a minimum standard for information in marketing
strategies (for example, the product's side effects and
specific warning notices).
 Supervision of medicinal product advertising is the
responsibility of the federal states.
 Because of the increasing need for consistent supervision, a
centralised co-ordination of supervision of the federal
states has been set up (Zentralstelle der Länder für
Gesundheitsschutz (ZLG)).

29. Restrictions…. Advertising
 Medicinal products cannot be advertised before the necessary
marketing approval is obtained (section 3a, Healthcare
Advertising Act). Further, advertising prescription medicinal
products to patients is prohibited (section 10, Healthcare
Advertising Act).
 The following issues, among other things, are prohibited:
 Misleading advertising.
 Gifts and other advertising giveaway.
 Promotional activities aimed at the general public must not
contain any advertising statements relating to prescription
medicinal products or to (severe) diseases explicitly mentioned
in the Healthcare Advertising Act (however, there are plans to
reduce the list of severe diseases).

30. Packaging and labeling

31. Packaging and labelling
 Legislation and regulatory authority
 Title V of Directive 2001/83/EC on the Community code relating to medicinal
products for human use, regulating the labelling of medicinal products for
human use and on package leaflets, has been implemented by the Drug Act
(sections 10 to 12, Drug Act).
 Labelling medicinal products used in clinical trials is regulated by the GCP
Ordinance (section 5, GCP Ordinance).
 The BfArM* has issued guidelines on labelling and on drafting text for labelling
according to section 11 of the Drug Act
(www.bfarm.de/cln_012/nn_1198876/SharedDocs/Bekanntmachungen/DE/Arzn
eimittel/natVerf/bm-zul-20061130-packungsbeilagen_2006-pdf.html).
 * Federal Institute for Drugs and Medical Devices

32. Packaging and labelling ,,,, Information
 Labelling of packages must contain, among other things
(section 10, Drug Act):
 The name or firm and the address of the pharmaceutical
company.
 The name and pharmaceutical form of the medicinal
product.
 The approval number, the description of charge, content of
the package (weight, size or number of units), the method
of application, the active ingredients, and the expiry date.
 Depending on the individual case: "prescription only",
"pharmacy medicines", "sample not for sale" and special
precautions.

33. Other conditions ,, Packaging and labelling
 The information for labelling must be well written,
generally understandable, durable and in German
language.

34. Traditional herbal medicines

35. Traditional herbal medicines
 Herbal medicinal products are deemed to be medicinal products
within the meaning of section 2 of the Drug Act and are subject
to the same legal requirements.
 there is a simplified re-registration procedure that allows
reference to the tradition of a medicinal product as a criterion for
efficacy of the product, which applies to a substantial number of
traditional herbal medicinal products (section 109a, Drug Act).

 A commission has been established under section 25, paragraph
7 of the Drug Act to consider documented evidence and reports,
and to produce lists of fields for which this procedure can be
applied. These lists were published in the Federal Gazette
(Bundesanzeiger) (see www.bundesanzeiger.de) and contain
about 1,000 substances.

36. Patents

37. Patents
 Medicinal products are capable of patent protection if
they are novel, involve an inventive step and are
capable of industrial application.
 Pharmaceutical inventions can be protected by
substance claims, process claims or use claims.
 The scope in terms of the prerequisite of novelty has
recently been revised by the German Supreme
Court.

38. Substance claims can relate to any of the following:
 An active compound of a pharmaceutical drug.
 A pharmaceutical composition containing an active compound.
 Interim products of a manufacturing process.
 Directive 98/44/EC on the legal protection of biotechnological
inventions (Biotech Directive) has been implemented in Germany, but
the legislator used its remaining discretion to limit patent protection in
this area. The basic rule is that plants and animal varieties, and
essential biological processes for the production of plants or
animals, are excluded from patent protection. However, the
following can be protected:
 Inventions that concern plants or animals not confined to a particular
plant or animal variety.
 Inventions that concern a microbiological or other technical process, or
a product obtained by means of such process.

39. How is a patent obtained? .. The authority
 Patent applications must be filed with either the:
German Patent and Trade Mark Office (Deutsches
Patent- und Markenamt) (PTO) (www.dpma.de).
European Patent Office (Europäisches Patentamt)
(EPO) (www.epo.org).
 Both offices are in Munich.

40. Fee …. patent
 The fees for a German patent are:
 EUR40 (about US$60) for online filings.
 EUR60 (about US$88) for other filings.
 EUR350 (about US$517) for the examination.
 EPO fees are:
 EUR100 (about US$148) for online filings.
 EUR180 (about US$266) for other filings.
 Designation fee for one or more Contracting State designated (Article
79(2), EPC): EUR500 (about US$739). Between EUR1,405 (about
US$2,076) and EUR1,565 (about US$2,312) for examination.
 Fee for patent grant: EUR790 (about US$1,167) (including fee for
printing the European patent specification up to 35 pages).

41. Process and timing ,,,patent
 The time frame for filing an application for a patent
depends on the technical field involved and the complexity
of the invention.
 According to the PTO, the procedure should be completed
within two and a half years, if the request for inspection
is filed within the first four months from the priority date
and the fees are paid in time. ( in some cases this period
can be extended)
 the European patent grant procedure takes about three to
five years from the date the application is filed.

42. Duration of protection ,,patent
 A patent is granted for a maximum 20-year term beginning on the day
following the filing of the application.
 A supplementary protection certificate can be obtained in some cases
to extend the duration of protection. Certificates are granted on a
national basis according to the formal and material requirements set
out in Regulation (EEC) No. 1768/92 concerning the creation of a
supplementary protection certificate for medicinal products. The
maximum extension period is five years. Under Regulation (EEC)
1901/2006 concerning medicinal products for paediatric use, this five
year protection period can be extended for another six months, if
both:
 The studies conducted to obtain approval for the medicinal product
comply with an agreed paediatric investigation plan.
 The medicinal product is authorised in all EU member states (however,
the interpretation of this condition is currently debated).

43. Renewal ,,,patent
 Renewal is not possible.

44. Trade marks
 the German Patent and Trade Mark Office
(DPMA)
 the Office for Harmonisation in the Internal
Market (OHIM)

45. Trade marks
 Marks comprising sufficient modifications of descriptive
indications can be registered as trade marks. This is especially
true for marks in the pharmaceutical field. However, the scope of
protection conferred is limited and does not extend to the
generic name or International Nonproprietary Name.
 Trade mark protection is excluded if a mark:
 Lacks distinctive character in relation to the goods or services for
which it claims protection.
 Consists exclusively of signs used to describe the kind, condition,
amount, or other features of the goods or services.
 The law of trade marks is set out in the Trade Mark Act
(Markengesetz).

46. How is a trade mark registered? The authority
 Applications for German trade marks must be filed
with the PTO (www.dpma.de)
 applications for Community Trade Marks (CTMs)
must be filed with the Office for Harmonisation in the
Internal Market (OHIM) (http://oami.europa.eu).

47. Fee ,,, Trade marks
The PTO fees are: the German Patent and Trade Mark Office
(DPMA)
 For up to three classes of registration: EUR300 (about US$443) or
online filing EUR290 (about US$428).
 For each additional class: EUR100 (about US$148).
 Accelerated examination: EUR200 (about US$295).
The OHIM fees are:
 Registration fee for up to three classes of registration: EUR1,050
(about US$1,551) or online filing EUR900 (about US$1,330).
 Registration fee for each additional class: EUR150 (about
US$222).

48. Process and timing ,,, trade marks
 After filing, an application is examined by the relevant
trade mark office. If no objections are raised, German trade
marks are usually provisionally registered within 10 to 12
months.
 An accelerated examination procedure is available, which
usually enables registration within three to four months.

 CTM* applications usually take about one year to
provisionally register. If no opposition is filed, the trade
mark is registered but is, under certain conditions, open to
cancellation proceedings.
 *Community Trade Marks

49.  German trade marks and CTMs* are registered for an
initial ten-year period. Registrations can be renewed
indefinitely for further ten-year terms.

 German trade marks and CTMs* can be cancelled if
they are not used within five years of registration.
 *Community Trade Marks

50. The regulatory authorities
 Federal Institute for Drugs and Medical Devices
(Bundesinstitut für Arzneimittel und
Medizinprodukte) (BfArM)
 Federal Agency for Sera and Vaccines (Paul-Ehrlich-
Institute) (PEI)

51. Federal Institute for Drugs and Medical Devices
(Bundesinstitut für Arzneimittel und Medizinprodukte)
(BfArM)
 T +49 228 99 307 30
F +49 228 99 307 5207
E poststelle@bfarm.de
W www.bfarm.de

52. Main areas of responsibility. The BfArM regulates medicinal products
(other than blood and vaccination products) for use on humans.
 Authorising finished medicinal products (that is, products that
have been manufactured and marketed in packaging ready for
distribution to consumers), including post-marketing
authorisation.
 Registering homeopathic products.
 Recording and assessing risk.
 Controlling legal marketing of narcotic drugs and precursors
(that is, chemical substances used to manufacture drugs).
 Advising the federal government.
 The sub-departments (Abteilungen) are:
 Departments 1 to 5: approval procedures.
 Department 6: scientific service.
 Department 7: pharmacovigilance.

53. Federal Agency for Sera and Vaccines (Paul-
Ehrlich-Institute) (PEI)
 T +49 6103 77 0
F +49 6103 77 1234
E pei@pei.de
Wwww.pei.de

54. Main areas of responsibility. The PEI authorises
the marketing and control of:
 Immune biological drugs for human and veterinary use, in particular sera.
 Vaccines.
 In vitro diagnostics for the detection of specific pathogens.
 Allergens.
 Test sera and test antigens.
 Blood preparations.
 Bone marrow preparations.
 Gene transfer medicinal products.
 Somatic cellular therapeutics.
 Xenogenetic cellular therapeutics.
 Genetically manufactured blood fractions.
 The PEI has a test laboratory for In Vitro Diagnostics (PEI-IVD). This is a notified body
within the meaning of the IVD Directive and deals with products listed in Annex II of the
IVD Directive. The objective of the PEI-IVD is to maintain the high level of safety of
blood and blood products set out in the IVD Directive.