Life Sciences 2021 Comparisons

Last Updated March 22, 2021

Contributed By Baker McKenzie

Law and Practice

Authors



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Pharmaceuticals for human use are governed by the German Drug Act (Arzneimittelgesetz, AMG), which in turn implements chiefly the European Directive 2001/83/EC. In addition, several important regulations govern the manufacture and distribution of pharmaceuticals as well as their use in clinical trials. Pharmaceuticals for veterinary use are currently also still governed by the German Drug Act, implementing Directive 2001/82/EC. However, as of 28 January 2022, the EU Regulation on Veterinary Medicinal Products (EU) 2019/6 will apply instead; legislation to adapt the German Drug Act is expected to be published in draft form, and ultimately adopted, in the course of 2021.

Medical devices are, as of March 2021, still governed by the Medical Device Act (Medizinproduktegesetz, MPG), which implements the medical device directives 90/385/EEC, 93/42/EEC and 98/79/EC, as well as by a number of regulations promulgated under the Medical Device Act. However, as the Medical Devices Regulation (EU) 2017/745 (EU MDR) will begin to apply to medical devices from 26 May 2021 onwards, the Medical Device Act will no longer apply, but will be replaced by the Medical Device Law Implementation Act (Medizinprodukterecht-Durchführungsgesetz, MPDG), which will complement the EU MDR. The same will apply from 26 May 2022 onwards for In vitro Diagnostics: The In Vitro Diagnostics Regulation (EU) (IVDR) 2017/746 will apply, complemented by the German Medical Device Law Implementation Act, and the currently applicable Medical Device Act will not apply to IVDs anymore, either.

Regulatory oversight over both pharmaceuticals and medical devices is divided between federal authorities and state level authorities.

With respect to pharmaceuticals, the federal regulatory authorities BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte) and PEI (Paul-Ehrlich-Institut) are responsible chiefly for issuing national marketing authorisations (MAs), approving clinical trials, and for pharmacovigilance: the PEI assumes these responsibilities for biological pharmaceuticals and advanced therapy medical products (ATMP), and the BfArM for all other pharmaceuticals. (Centralised MAs are issued by the EU Commission based on the evaluation of the European Medicines Agency (EMA).) The state level authorities are chiefly responsible for issuing manufacturing, wholesale distribution, and import licences, and for overseeing, for ascertaining through inspections and for enforcing compliance with applicable pharmaceutical laws.

With respect to medical devices, the BfArM is responsible chiefly for classification decisions, clinical trial approvals, and vigilance, whereas the state level authorities are responsible for general oversight, inspections, and enforcement.

The BfArM and the PEI are subject to oversight by the federal Ministry of Health, which has the authority to issue directives to the BfArM and the PEI. The same applies mutatis mutandis to state level authorities.

Enforceable decisions by regulatory bodies qualify as administrative acts which can be challenged by the addressee (or by a third party having standing) by lodging an objection with the regulatory body which has issued the administrative act. By default, the objection has suspensory effect and impedes enforcement of the challenged administrative act. However, the regulatory body can order the immediate execution of the administrative act, notwithstanding the pending objection. In such a case, the addressee of the administrative act (or a third party having standing) can submit a request to the competent administrative court to (re-)establish the suspensory effect of the objection, which, if successful, precludes enforcement until a final decision is obtained: either the objection sustained by the regulatory body, or otherwise, upon filing a lawsuit against the administrative act and the unsuccessful objection proceeding, the administrative act either confirmed or lifted by the administrative courts.

Objections against administrative acts, as well as requests for (re-)establishing suspensory effect and lawsuits, must be lodged in writing and within one month of notification of the decision to be challenged.

The aforementioned procedure applies to pharmaceuticals and medical devices as well as to other regulated products.

Pharmaceuticals may qualify as prescription-only, pharmacy-only, and freely sellable pharmaceuticals. Prescription-only medicinal products may not be advertised to the public and, like pharmacy-only pharmaceuticals, only be dispensed by pharmacies (including online/mail-order pharmacies).

The same three-pronged distinction applies to medical devices. However, unlike pharmaceuticals, most medical devices are freely sellable and not qualified as prescription-only or pharmacy-only.

Clinical trials with pharmaceuticals are governed by the AMG and the German GCP Regulation. Once the European Clinical Trial Regulation (EU) No 536/2014 (CTR) applies (expected by early summer 2022), clinical trials with pharmaceutical will primarily be governed by the CTR; the provisions of the AMG on clinical trials will be substantially modified to complement the CTR rules, and the German GCP Regulation will be repealed.

Clinical trials with medical devices are as of March 2021 governed by the MPG and the Regulation on Clinical Trials with Medical Devices (MPKPV). Those regulations will be replaced by the EU MDR/IVDR and the German Medical Device Law Implementation Act (MPDG), which will govern clinical trials with medical devices from 26 May 2021 onwards and for clinical trials with in vitro diagnostics from 26 May 2022 onwards.

Under the current regulations, clinical trials require prior authorisation by the federal regulatory authority BfArM (for biological pharmaceuticals, the ATMP and certain IVDs, the PEI) and positive opinion by the competent ethics committee. The focus of the authorisation procedure before the federal regulatory authority is the quality, efficacy/performance and safety of the investigational pharmaceutical or device. The focus of the review by the ethics committee is the ethical and scientific justification of the clinical trial, taking particularly into account the rights of the trial participants.

Non-interventional clinical studies are excluded from the scope of the aforementioned regulations, but may under the applicable state laws and regulations require involvement of the ethics committee of the local physicians' association.

The sponsor must submit:

  • an application for authorisation of the clinical trial to the competent federal regulatory authority (the BfArM or the PEI), as well as:
  • an application for favourable opinion to the ethics committee which is competent under applicable state law for the principal investigator.

The applications regarding clinical trials with pharmaceuticals can be submitted in writing (with electronic copies of the application and supporting documentation provided) or electronically through the Common European Submission Portal (CESP). The applications regarding clinical trials with medical devices shall both be submitted electronically through the German Institute of Medical Documentation and Information (DIMDI) portal. The competent federal regulatory authority as well as the ethics committee each acknowledge receipt within ten days and in the case of formal deficiencies request their remediation within 14 days.

Formally completed applications for clinical trial authorisation are considered approved if the competent federal regulatory authority does not object within 30 days. An objection triggers a 90-day remediation period for the applicant to revise the application; the federal regulatory authority will issue its final decision with 15 days of receipt of the revised application. As an exception to these rules, applications for authorisation of clinical trials with certain pharmaceuticals of higher risk or complexity always require an explicit authorisation by the federal regulatory authority, which shall be issued within 60 days. In these cases, if the applicant needs to revise the application following an objection by the federal regulator, the federal regulatory authority will decide on the revised application within another 30 days.

Formally completed applications for favourable opinion to the ethics committee are decided upon within 60 days. The ethics committee may request additional information from the applicant once only. Until the receipt of any such information, the clock is stopped.

Subsequent significant changes to the approved clinical trial may only be implemented after prior approval by the federal regulatory authority and/or the competent ethics committee, as applicable, depending on the subject matter of the change.

Clinical trial authorisations as well as favourable ethics committee opinions can be suspended or revoked if the conditions for approving of the clinical trial are no longer met.

For medicines, information on approved clinical trials available on the German PharmNet.Bund database and also submitted by the federal regulatory authority to the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) database maintained by the European Medicines Agency. The clinical trial information in the EudraCT database is publicly accessible under www.clinicaltrialsregister.eu.

Under current German law, sponsors must submit within six months of completion a report of the clinical trial results, which is then published on PharmNet.Bund. Under the EU CTR (which will likely become applicable in mid-2022), substantially more information on the clinical trial will be made publicly available through the EU clinical trial portal.

Already today, the EMA publishes in accordance with its Policy 0070 clinical data which pharmaceutical companies have submitted to support their centralised MA applications under clinicaldata.ema.europa.eu.

Information on clinical trials with medical devices is currently not made available in free public databases. However, the EU MDR and IVDR provide for transparency of clinical trial information through the European Databank on Medical Devices (Eudamed) database. The obligations of sponsors of clinical trials with medical devices to submit clinical trial results will come into force six months after publication of the notice that the clinical investigations and performance studies module of the Eudamed database is functional (the EU Commission has not yet announced an estimated date).

There are no particular German regulations on the use of online tools to support clinical trials. Generally, any use of clinical trials must comply with data protection requirements under the General Data Protection Regulation (GDPR) and applicable implementing and complementing German laws on federal and state level.

The clinical trial data directly generated in the trial – whether in "raw" form as maintained at the clinical trial site or in pseudonymised form as subsequently transferred from the clinical trial centre to the sponsor – is considered "special categories of personal data". Their processing is conditioned to higher requirements set out in Article 9 (2) of the GDPR. Only anonymised data do not fall under the requirements of the GDPR, but anonymised clinical data are of limited use and the requirements for anonymisation are high. In practice, clinical trial participants provide their informed consent to their participation in the clinical trial and the processing of their data by signing informed consents as approved by the competent ethics committee in the clinical trial authorisation procedure.

A transfer of clinical data which falls under the GDPR (ie, non-anonymised data) is generally only possible if covered by the informed consent of the trial participants. Whether – in the absence of express informed consent by the trial participants – the transfer of such data can also be justified by purposes of scientific research under Article 9 (2) lit. j of the GDPR is being discussed, but has not yet been definitively decided and will depend on the specific situation.

The creation of a database containing personal data of trial subjects would need to comply with the requirements set out in the GDPR. Notably, the trial participants need to be informed about the use and storage of their data in such a database, and the database must meet applicable data security requirements. To the extent that the database is operated by a third party, that third party must itself comply with the GDPR. To the extent that the database is hosted outside the EU, or data are otherwise transferred outside the EU, the rules and European Court of Justice (ECJ) case law regarding the transfer of personal data out of the EU must be complied with.

German law defines pharmaceuticals as substances which are intended to treat, mitigate or prevent diseases, or to restore, correct or modify physiological functions through a pharmaceutical, immunological or metabolic effect, or to make a medical diagnosis. Medical devices, in turn, are defined as products - including devices, instruments, in vitro diagnostics, software, but also substances – which are intended for a medical use, but which achieve their principal intended action in or on the human body by other means than pharmacological, immunological or metabolic means.

Accordingly, the key criterion for classifying borderline products as either pharmaceutical or medical devices depends on (i) identifying the principal intended action, and (ii) analysing whether such action is achieved by pharmacological, immunological or metabolic means. In practice, the interpretation of these terms in the so-called "MEDDEV" (Medical Devices Documents) guideline published by the EU carries substantial weight. Further guidance is provided in the so-called "Borderline Manual" (Manual on Borderline and Classification in the Community Regulatory Framework for Medical Devices), also published by the EU.

The responsibility for appropriately classifying a product lies with its manufacturer. If a product is granted an MA as a pharmaceutical, it will necessarily be considered as a pharmaceutical as long as the MA is in force. Inversely, however, CE-marking a product after conformity assessment in accordance with medical-device law does not ensure that the implied classification as medical device is upheld if challenged by regulators or by competitors in court. However, a manufacturer or state supervisory authorities can apply with the BfArM for a binding decision whether or not a given product qualifies as a medical device.

German law does not in principle provide for different MA procedures for biological medicinal products (unlike, eg, the USA). However, the requirements regarding the contents of the dossier is different from biological medicinal products, owing to the importance of the manufacturing process of the biological medicinal product. Similarly, the MAs of biosimilars require substantially more documentation than MAs for generics of non-biological originator medicines.

Procedurally, MAs for biological medicinal products – provided they are not authorised by the EU Commission under an EU-wide centralised MA – are granted by the PEI rather than the BfArM (see 1.1 Legislation and Regulation for Pharmaceuticals and Medical Devices).

MAs are issued for an initial period of five years. If renewed upon request at least nine months prior to the expiry of its initial term, the MA remains valid for an unlimited period of time. The MA may upon renewal only be limited again for a five-year-period if the initial five-year period did not provide sufficient real-life data to guarantee the safety of the product.

An MA can be suspended or revoked if legal requirements for the MA, eg, the safety, efficacy, and quality, are not met or are no longer met. Furthermore, an MA can be revoked under the "sunset clause" if the authorised pharmaceutical is not placed on the market within three years of the issuance of the MA or its marketing suspended for a period of three years.

For medical devices, certificates issued by notified bodies which support the CE-marking of the medical device by the manufacturer have a validity of up to five years. Certificates issued by notified bodies can be reduced in scope, suspended or revoked by the notified body if the requirements for issuance of the certificate are not met or are no longer met.

An MA for a pharmaceutical can be obtained:

  • in the centralised procedure through an application to the European Medicines Agency, with a view to obtaining a centralised MA valid in the entire EU. The European Medicines Agency (EMA) shall give an opinion on the application within 210 days. The opinion is the basis for the decision by the European Commission to grant the central MA;
  • in the national procedure through an application to the BfArM (or to the PEI for biological pharmaceuticals), with a view to obtaining a national MA valid in Germany. The statutory timeframe for issuing the MA is seven months upon receipt of a complete application. Where a national MA is to be applied for in several member states (decentralized procedure, DCP), the reference member state will draw up a draft assessment within 120 days, and each member state shall take a decision within 90 days of receipt of these drafts. Where a national MA for the medicine has already been issued in another member state, that member state shall submit within 90 days an up-to-date assessment of the approved assessment to the German authority, which shall take a decision on the application based on the other state's assessment within another 90 days (mutual recognition procedure, MRP).

Variations to MAs for pharmaceuticals are submitted electronically to the competent regulatory authority (the EMA, the BfArM, or the PEI). Depending on their impact to the safety, quality, and efficacy of the product, variations are classified as IA, IB or II. The former only require a notification, the latter prior approval.

Centralised MAs can be transferred following the procedure set out in Regulation (EC) No 2141/96. MAs issued by German authorities are transferred by contractual agreement between the current holder and future holder, and the new MAH is subsequently notified to the competent federal regulatory authority (the BfArM or the PEI).

For medical devices, the CE mark may be affixed to the device once the manufacturer has conducted a conformity assessment. Depending on the risk-classification of the medical device, the conformity assessment requires the involvement of a notified body and the issuance of the certification by that notified body. A transfer of the CE mark is not possible legally; rather, the new manufacturer of the medical device must themselves obtain and meet all the requirements necessary to CE-mark the medical device under their own name.

Pharmaceuticals which require an MA but are not authorised (yet) may only be supplied to patients in the following circumstances:

  • clinical trials;
  • compassionate-use programmes for patients with a chronically or seriously debilitating disease or whose disease is considered to be life-threatening, and who cannot be treated satisfactorily by an authorised medicinal product. The pharmaceutical concerned must either be the subject of a pending marketing-authorisation application or must be undergoing clinical trials. In Germany, pharmaceuticals supplied under a compassionate-use programme may only be supplied free of charge;
  • named-patient programme: upon prescription for a specific patient, pharmacies may import and dispense to that patient a limited quantity of medicinal products which are authorised in the country of export but not in Germany, if no comparable medicines are available in Germany. A named-patient programme does not need to be authorised or notified to a regulatory authority.

German medical-device law does not provide for compassionate-use programmes or named-patient exceptions for medical devices which need to bear a CE mark.

For pharmaceuticals, the MAHs must discharge several ongoing obligations, including the following:

  • maintain the dossier of the product up to date and notify, or submit variations to, the competent regulatory authority if the particulars set out in the MA change;
  • set up, maintain and audit a pharmacovigilance system, appoint a qualified person for pharmacovigilance (Stufenplanbeauftragter), maintain a pharmacovigilance master file, operate a risk-management system for the pharmaceuticals, document and report suspected adverse reactions, monitor scientific literature for safety signals, prepare and submit periodic safety update reports;
  • appoint an information officer (Informationsbeauftragter) who is responsible for ensuring that the product labelling, package-insert leaflets, and summary of product characteristics, as well as all promotional material, is in line with the terms of the MA;
  • take out and maintain product liability insurance which fully covers the specific statutory no-fault liability of the MAH under the German Drug Act.

Under current medical-device law, manufacturers of medical devices, ie, who are indicated as the manufacturer in the labelling, are subject to technovigilance reporting obligations and, if their place of business is in Germany, they must appoint a safety officer (Sicherheitsbeauftragter). Further ongoing obligations for post-market surveillance can be derived from the manufacturer's quality system, which typically implements the requirements of the technical standard ISO 13485:2016.

The EU MDR and IVDR, which become applicable on 26 May 2021 and 26 May 2022, respectively, set forth more ongoing obligations, including: manufacturers must appoint a person responsible for regulatory compliance(PRRC), maintain and provide unique device-identifier (UDI) information to improve traceability of medical devices, conduct post-market clinical follow-up (PMCF) activities, prepare post-market surveillance reports or regular periodic safety update reports, and prepare trend reports on safety signals.

Whereas the EMA does publish a list of "medicines under evaluation", the German federal regulators do not proactively publish pending MA applications under review. Details about approved pharmaceuticals are available in a public database (Arzneimittel-Informationssystem).

Requests for information about pending, granted or rejected MA applications can be submitted to the BfArM or the PEI under the German Freedom of Information Act (Informationsfreiheitsgesetz, IFG). However, to the extent that the requested information contains personal data, is protected by intellectual property rights or constitutes confidential business information, that information will be redacted or will not be disclosed. The authority will typically ask the MAH whether he or she consents to the requested disclosure and allow for comment on the proposed redactions. Generally, the German regulatory authorities are more protective of the MAH's information than the EMA.

As medical devices are, under current medical-device law, not subject to a governmental approval process, any information about medical devices undergoing conformity assessment remains with the manufacturer and the Notified Body who, as private parties, are not subject to the Freedom of Information Act. For medical devices placed on the market in Germany and notified to the BfArM, a limited set of information is accessible through dimdi.de. Under the EU MDR and IVDR, more information will become publicly available through the European Database for Medical Devices (EUDAMED) database which is currently only accessible to regulatory authorities.

With respect to pharmaceuticals, the Falsified Medicines Directive 2011/62/EU has been implemented into German drug law:

  • to prevent falsified prescription-only medicines entering the supply chain, prescription-only medicines must bear an anti-tampering device (eg, a sealing strip) which allows verification that the pack has not been opened, and a unique identifier to verify the authenticity of the pack (serialisation); the details are set forth in the Delegated Regulation (EU) 2016/161;
  • the import and distribution of falsified pharmaceuticals in Germany is expressly prohibited and is subject to penal sanctions. The regulatory authorities are authorised to take enforcement action against falsified medicines, including seizure;
  • MAHs, wholesale distributors, and pharmacies are subject to increased control and notification obligations to identify and report falsified medicines.

Current German medical-device law does not specifically address falsified medical devices. However, the state supervisory authorities may take enforcement action where devices are unlawfully CE-marked or present a safety or health risk. Upon application of the EU MDR and IVDR, importers and distributors have the obligation to inform the competent authorities of suspected falsified devices. The authorities may, where necessary to protect the public health, confiscate, destroy or otherwise render inoperable any such falsified devices.

The Federal Ministry of Finances and the customs authorities are competent for enforcing German drug law with respect to pharmaceuticals imported from (or exported to) non-EU countries. The customs authorities will verify upon import the relevant import documentation, including whether a certificate attesting that the manufacture in the country of export complies with good manufacturing practices. If in doubt, the German customs authorities will liaise with the German regulatory authorities. German customs authorities regularly report on the numbers and types of intercepted counterfeit pharmaceuticals.

Similarly, the German customs authorities are competent for enforcing compliance of imported medical devices with the applicable law in accordance with Regulation (EC) No 765/2008. The German customs authorities will liaise with the competent German regulatory surveillance authorities if a medical device:

  • displays characteristics which give cause to believe that the device presents a serious health or safety risk;
  • is not accompanied by the required documentation or not marked as required; or
  • has a CE mark that has been affixed to the device in a false or misleading manner,

to determine further action.

In addition to the foregoing, border measures can be based on IP rights (see 10.1 Counterfeit Pharmaceuticals and Medical Devices).

The manufacture of pharmaceuticals (which includes also packaging, labelling and final release of the finished product) is subject to a manufacturing authorisation.

The authorisation is granted by the competent authority of the federal state in which the manufacturing site is located. In order to obtain a manufacturing authorisation, the applicant must:

  • appoint a Qualified Person (QP), as well as a Head of Production and a Head of Quality Control, each of whom must be appropriately qualified; the QP must also be experienced and reliable, to be evidenced through a clean criminal record certificate;
  • have other appropriately qualified and trained personnel to conduct the manufacturing activities;
  • have the appropriate premises for performing the manufacturing activities; and
  • set up and maintain a quality system, consisting of standard operating procedures, which covers the manufacturing activities, and have the staff trained to its content.

The manufacturing licence will only be issued after a successful on-site inspection of the manufacturing premises by the regulatory authority. The statutory timeframe for issuing a manufacturing licence is three months from the submission of a complete application. However, follow-up requests by the authority or deficiencies identified in the inspection stop the clock.

The manufacturing authorisation is granted for a specific site and typically for specific manufacturing activities and types of medicines, sometimes covering only individually specified medicinal products. It is issued for an unlimited time, but remains subject to regular Good Manufacturing Practice (GMP) inspections by the competent authority.

The manufacture of medical devices is not subject to a governmental authorisation. The quality of the manufacturing processes is regulated indirectly through the conformity assessment of the respective device and the manufacturer's quality system which supports the conformity assessment.

The wholesale distribution of pharmaceuticals is subject to a wholesale distribution licence (WDL). Wholesale distribution is not limited to the physical handling and storage of pharmaceuticals. A WDL is also needed for procuring, selling, and supplying pharmaceuticals, even when the physical handling and logistics are outsourced to a third party. However, a manufacturer does not need a WDL for supplying and distributing pharmaceuticals which it has manufactured; any such supply and distribution is covered by the manufacturing licence.

The WDL is granted by the competent authority of the federal state in which the wholesale distribution site is located. In order to obtain a WDL, the applicant must:

  • appoint a Responsible Person for wholesale distribution (RP), who must be appropriately qualified, experienced and reliable, the latter to be evidenced through a clean criminal record certificate;
  • have other appropriately qualified and trained personnel to conduct the wholesale distribution activities, as necessary;
  • have the appropriate premises for performing the wholesale distribution activities; and
  • set up and maintain a quality system, consisting of standard operating procedures, which covers the manufacturing activities, and have the staff trained to its content. This quality system shall in particular ensure that medicines are only sourced from, and supplied to, entities which are authorised to supply or procure such medicines, that all procurement and supply of pharmaceuticals is properly documented, and that recalls can be implemented.

The WDL will only be issued after a successful on-site inspection of the wholesale distribution site by the regulatory authority. The statutory timeframe for issuing a WDL is three months from the submission of a complete application. However, follow-up requests by the authority or deficiencies identified in the inspection stop the clock.

As with a manufacturing authorisation, the WDL is granted for a specific site, for specific distribution activities and for specific types of medicines (including or excluding, eg, blood products, controlled substances, or temperature-controlled products). It is issued for an unlimited time, but remains subject to regular GDP inspections by the competent authority.

The distribution of medical devices is not subject to a governmental authorisation, nor currently regulated in detail. However, under the EU, MDR and IVDR distributors will be subject to certain obligations to ensure that only compliant medical devices are made available on the market (cf Article 14 of the EU MDR).

See 1.3 Different Categories of Pharmaceuticals and Medical Devices.

The import and export of pharmaceuticals is governed by the German Drug Act (AMG), notably its Sections 72 et seq.

The import of medical devices is regulated in the German Medical Device Act (MPG) insofar as it assigns regulatory responsibility to the importer where the manufacturer is not established in the EU and has not assigned an authorised representative (see 6.3 Prior Authorisations for the Importation of Pharmaceuticals and Medical Devices).

In order to import from outside the EU and EEA member states into Germany or to export from Germany outside the EU/EEA, an operator is required to have an EORI-number (EU-wide applicable customs registration number). Applying for a customs credit (deferred payment) and possibly providing a customs guarantee may allow the applicant to benefit from simplified customs operations (eg, electronic customs declarations, payment of duties online, simplified procedures, etc). In addition, an operator may choose to apply for the status of Authorised Economic Operator (AEO), which should entail a pre-approval for most customs authorisations.

With respect to regulatory requirements, see 6.3 Prior Authorisations for the Importation of Pharmaceuticals and Medical Devices.

Pharmaceuticals may only be imported from outside the EU and the EEA member states (Norway, Iceland, and Liechtenstein) into Germany if an MA for any such pharmaceutical is in place and if the importer holds an import authorisation. The issuance, scope, and resulting obligations of an import authorisation are analogous to a manufacturing authorisation (see 4.1 Requirement for Authorisation for Manufacturing Plants of Pharmaceutical and Medical Devices). Exemptions from the requirements of an MA and an import authorisation requirement apply, inter alia, to:

  • pharmaceuticals for the importer's own scientific use (except for clinical trials);
  • pharmaceuticals imported in small quantities by the MAH or an authorised manufacturer as samples or for analytical purposes;
  • pharmaceuticals imported by an authorised manufacturer for further processing;
  • pharmaceuticals imported by an MAH, authorised manufacturer or wholesale distributor intended for further shipment into other EU member states;
  • pharmaceuticals imported in small quantities for personal use;
  • samples imported for use by regulatory authorities; and
  • imports by pharmacies in connection with a "named-patient programme" (see 3.5 Access to Pharmaceutical and Medical Devices without Marketing Authorisations).

The import of medical devices from outside the EU and the EEA member states into Germany does not require a governmental authorisation. However, the imported medical devices must be lawfully CE-marked, based on a complete conformity assessment, and the importer will bear the regulatory responsibility for the device if the manufacturer is based outside the EU/EEA and has not appointed an authorised representative. Under the EU MDR and IVDR, the importer will be subject to additional obligations to ensure that only compliant medical devices are imported and made available on the market (cf Article 13 of the EU MDR).

The applicable non-tariff regulations depend on whether or not an imported product qualifies as a pharmaceutical, a medical device or another type of product. This in turn depends on whether that product meets the statutory product definition under the German Drug Act or the applicable medical-device regulations (for details, see 1.1 Legislation and Regulation for Pharmaceuticals and Medical Devices and 3.1 Product Classification: Pharmaceutical or Medical Devices).

Germany is a member of the EU and thus participates in the free trade arrangements concluded by the EU, and is a member of the World Trade Organization (WTO).

Pharmaceuticals

The German Drug Act (AMG), notably its Section 78, and the German Drug Pricing Regulation (Arzneimittelpreisverordnung, AMPreisV) set out whether or not pharmaceuticals are subject to price controls and, if so, also sets out the margins of wholesalers and pharmacies. Generally, only prescription-only pharmaceuticals which are dispensed in pharmacies are subject to price controls and fixed margins. Non-prescription pharmaceuticals as well as prescription-only pharmaceuticals dispensed to hospitals are exempt from the general statutory price controls.

Under German constitutional law, the pharmaceutical company is free to set its sales price. However, the public health insurance funds are not obliged to reimburse such prices in full. Rather, for pharmaceuticals which are subject to price control under the German Drug Act (AMG) and German Drug Pricing Regulation (AMPreisV), the German Social Code V (Sozialgesetzbuch V, SGB V), which regulates the public health service and public health insurance system that covers approximately 90% of the German population, provides for several price-control mechanisms:

Early benefit assessment and reimbursement price negotiations (AMNOG)

As of 1 January 2011, the so-called AMNOG law has introduced a price-control mechanism for pharmaceuticals with a new active substance. Reimbursement prices for such innovative pharmaceuticals are negotiated between MAH and the umbrella organisation of the German health insurance funds (GKV-Spitzenverband) on the basis of a so-called "benefit assessment". The process has two consecutive preparatory phases of six months each, and therefore only kicks in after the first full year since market launch.

  • Phase 1 (months one to six since product launch): upon the launch of the medicine on the German market, the MAH must submit a dossier demonstrating (through clinical evidence) the additional therapeutic benefit of the new medicine by comparison to the current standard therapy. Orphan drugs enjoy certain exemptions from this requirement if the annual out-patient turnover in Germany does not exceed EUR50 million. Based on the assessment of the data in the submitted dossier, a joint body of the German public health insurance system (Gemeinsamer Bundesausschuss, GBA) determines the scope and degree of the additional therapeutic benefit of the new medicine.
  • Phase 2 (months seven to 12 since product launch): the additional therapeutic benefit determined by the GBA is a key factor for subsequent reimbursement price negotiations between the MAH and GKV-Spitzenverband during the months seven to 12 since launch. The agreed reimbursement price will apply for all patients in Germany (including the privately insured) from the 13th month since the market launch onwards. If the MAH and GKV-Spitzenverband fail to agree on a reimbursement price for the new medicine, a reimbursement price will be unilaterally set by an arbitration board, with retroactive effect to the 13th month since the market launch.

In the first year of the marketing and until the reimbursement price kicks in at the beginning of the 13th month since the market launch, the new medicine will by default be reimbursed at the price set by the MAH.

Reimbursement price caps for established therapeutic classes

The GBA can establish therapeutic classes of pharmaceuticals that cover a group of pharmaceuticals of similar or comparable active substance and comparable therapeutic effect. For each class, GKV-Spitzenverband will set, and review annually, reimbursement price caps, which generally lie in the lower third of the range between the lowest price and the highest price of all pharmaceuticals in that class. Public health insurances will only reimburse these pharmaceuticals up to the cap; if the MAH sets a higher price, the patient will need to pay the difference. This price control primarily, but not exclusively, affects generics.

Statutory rebates

MAHs must reimburse a statutory rebate of 7% (for patent-protected pharmaceuticals) and 16% (for generics) to public health insurance funds. Statutory rebates do not apply for pharmaceuticals in established therapeutic classes subject to the reimbursement price caps.

Price freeze

Since 1 August 2010,MAHs must pay back to public health insurance funds any increase in price beyond the price effective on 1 August 2009. Since 1 August 2018 going forward, the price level will be adjusted annually for inflation. The price freeze does not apply where a reimbursement price is set based on the early benefit assessment or capped for an established therapeutic class.

The prices for pharmaceuticals which are not covered by Section 78 of the AMG and AMPreisV can be negotiated freely.

Medical Devices

German medical-device law does not provide for price controls. German public healthcare law, in turn, does not provide for a common reimbursement and pricing mechanism for all medical devices. Rather:

  • where medical devices are part of the outpatient medical therapy (eg, ophthalmic medical devices which can be implanted in an out-patient setting), the healthcare-provider is generally reimbursed for the purchase price by the public health insurance fund; however, regional collective agreements may provide for particular reimbursement requirements and price caps;
  • medical devices prescribed by a healthcare-provider which serve to secure the medical therapy, or mitigate or compensate the effects of injuries, are qualified as auxiliary devices (Hilfsmittel). Suppliers of auxiliary devices must meet pre-qualification requirements and enter into supply agreements with public health insurance funds in order to be entitled to supply, and be reimbursed for, auxiliary devices to insured patients. Furthermore, auxiliary devices may be grouped in established therapeutic classes similarly to pharmaceuticals as previously stated, with a view to capping the reimbursement price.

The actual sales price in other European countries shall be taken into account in the AMNOG reimbursement price negotiations for innovative pharmaceuticals (see 7.1 Price Control for Pharmaceuticals and Medical Devices).

90% of the German population is enrolled in the statutory health system. These patients have a right to be provided with all treatments, including pharmaceuticals and medical devices, which are medically necessary, sufficient and cost-effective. This means that the coverage of pharmaceuticals is generally limited to prescription-only medicines, and the cost is controlled through various statutory price control mechanisms (see 7.1 Price Control for Pharmaceuticals and Medical Devices) and by tenders of the health insurance companies.

The additional benefit of novel pharmaceuticals by comparison to the standard therapy is a key factor in negotiating the reimbursement price (see 7.1 Price Control for Pharmaceuticals and Medical Devices).

Physicians are subject to various mechanisms to ensure that their prescribing of pharmaceuticals is cost-efficient. Physicians who prescribe excessively may be required to pay damages to the public healthcare system.

In order to curb pharmaceutical spending, pharmacies must observe several substitution rules designed to increase the dispensing of generics or cheaper parallel-imported pharmaceuticals instead of originator products. A pharmacist who fails to comply with those substitution rules must pay back to the public healthcare system the full price of the dispensed product, without the option to offset the theoretical cost of the cheaper alternative that should have been dispensed under the substitution rules.

Medical apps may qualify as medical devices if the app meets the definition of a medical device (see 3.1 Product Classification: Pharmaceutical or Medical Devices). The MEDDEV guideline 2.1/6 on the qualification and classification of standalone software offers additional criteria to operationalise the general medical-device definition for software. A key criterion within the five-step decision tree proposed by the MEDDEV guideline is whether the app performs actions on data for a specific patient which goes beyond mere storage, archival, lossless compression, communication, or simple search. A test is whether the app creates or modifies medical information through its own algorithm.

If a medical app qualifies as a medical device of class I or IIa, that medical app can qualify as a Digital Health Application (DiGA) and be eligible for prescription by physicians and reimbursement by the public health insurance system ("app on prescription"). This reimbursement mechanism for medical apps was introduced in late 2019 and is the first statutory reimbursement mechanism for medical apps in the world. In order to be included in the DiGA Directory of reimbursable apps, the manufacturer of the DiGA must submit an application to the BfArM, showing that:

  • the main function and medical purpose of the DiGA is based on digital technologies and functions;
  • beyond security and functionality (evidenced through the CE mark), quality, data protection, data security and inter-operability requirements are met; and
  • the use of the DiGA provides positive care effects (medical benefit, structural and procedural improvements).

If positive care effects are not excluded, but supporting data is not yet available, DiGAs can be temporarily admitted to the DiGA Directory for up to 12 months to generate that data. Once the data is available, the reimbursement price for the DiGA will be negotiated in a process which is comparable to the AMNOG procedure for novel pharmaceuticals (see 7.1 Price Control for Pharmaceuticals and Medical Devices).

German doctors in most states may provide telemedicine services where face-to-face patient contact is not medically required. In 2019, the anachronistic prohibitions to advertise for such telemedicine services and to dispense medicines prescribed through a telemedicine services have been lifted.

In the public healthcare system, the telemedicine services which are reimbursed to the doctors is currently limited, but growing. The collective agreement between GKV-Spitzenverband and the doctors' head association sets out requirements on patient authentication, data privacy and quality requirements for the telemedicine service-provider that must be complied with in the public healthcare system.

There are no special rules for the online promotion and/or advertising of medicines and medical devices. Rather, companies promoting their medicines or medical devices online must comply with all applicable requirements, including advertising limitations set forth in the Health Product Advertising Act (Heilmittelwerbegesetz, HWG), pharmacovigilance obligations, and data privacy and telecommunications laws.

From a regulatory perspective, German drug law (German Drug Prescription Regulation, AMVV) and German medical-device law (German Medical Device Dispensing Regulation, MPAV) already allow for prescriptions to be issued electronically and be signed by electronic qualified signature. Pharmacy law also already allows pharmacists to accept electronic signatures.

From a reimbursement perspective, though, the public healthcare system has so far not provided for the processing and invoicing for reimbursement of electronic prescriptions. However, new legislation introduced in 2020 provides that electronic prescriptions will be introduced and recognised in the public healthcare system from 1 January 2022 onwards.

Medicines and medical devices may be sold online. German pharmacies may also sell both prescription-only and pharmacy-only medicines online if:

  • the pharmacist also holds a mail-order pharmacy permit (Versandhandelserlaubnis); and
  • the mail-order business is conducted "out of the pharmacy" in addition to the retail pharmacy business. Mail-order pharmacy activities without running a "bricks-and-mortar" pharmacy are not permitted in Germany.

In addition to German pharmacies, several Dutch online pharmacies located at the Dutch/German border supply the German market, leveraging the free movement of goods within the EU.

In the public health system, which covers approximately 90% of the German population, the electronic patient file (ePA) is being rolled out during 2021, currently on a voluntary basis, and shall be fully functional by 2022. The ePA is regulated in the Social Code V (see 7.1 Price Control for Pharmaceuticals and Medical Devices).

As electronic health records qualify as "special categories of personal data" under the GDPR, the considerations on clinical trial data in 2.5 Use of Resulting Data from the Clinical Trials apply mutatis mutandis to electronic health records.

In Germany, the Patent Act contains the relevant provisions for patents.

There is a huge variety of general patent law issues, which can become relevant for pharmaceutical and medical device products, ranging from the determination of the widest possible scope when applying for a patent to a potential infringement under the doctrine of equivalents in infringement proceedings. In addition, the specific provisions regarding a second and subsequent medical use, as well as the extension of the patent term by way of a supplementary protection certificate set out in 9.3 Patent Term Extension for Pharmaceuticals, often play an important role. Not strictly resulting from patent law provisions, yet of high relevance in patent strategies and litigation, agreements between originators and generic entrants may also be considered as anti-competitive.

There are no specific patentability requirements for pharmaceuticals or medical devices as such. Even though methods for treatment by surgery or therapy and diagnostic methods are not patentable, the use of substances in these methods is explicitly not covered and thus patentable. Further restrictions regarding patentability relate to processes for cloning human beings and for modifying the germinal genetic identity of human beings.

A second or subsequent medical use is patentable if the medical indication is new. Therefore, the type of application or the area of use must not be previously known.

However, generally, it is not sufficient to modify the dosage regime even if this improves the effectiveness of the drug. Notwithstanding, the discovery of the use for new patient populations is patentable if the new patient group can be clearly distinguished from the previously known group.

The preparation and use of the drug for the claimed (second or subsequent) use constitutes patent infringement regarding the (new) patent. Preparation for such use can result from instructions for use delivered with the drug. Nevertheless, the drug can be used in a non-infringing manner for the previously known purpose, provided that this application is not protected (anymore). If there is a prior product patent with broad claims, the patent covering a second or subsequent use may be a dependent invention.

The patent-holder of an authorised medicinal product can apply for a supplementary protection certificate (SPC) within six months from the grant of the marketing authorisation. The SPC can extend the protection term by the time that elapsed between the application for the patent and the marketing authorisation, reduced by five years. This potential extension is limited to five years, plus six months in cases with completed studies in compliance with an agreed paediatric investigation plan. For each medicinal product, only one SPC can be granted and the product must be covered by a first marketing authorisation.

Generally, the certificate confers the same rights as the basic patent with certain limitations regarding the intended export of the products.

Any third party can bring an action for declaration of invalidity of the certificate before the German Federal Patent Court, according to Section 81 of the German Patent Act.

As for any product patent, infringing actions include the manufacturing, offering, placing on the market or use of a product, as well as importing or possessing it for the aforementioned purposes. Advertising a product may also infringe a patent, even if the advertising only relates to subsequent distribution after the lapsing of the patent.

In order to get injunctive relief, the infringement must be (at least) imminent. The application for marketing authorisation is not considered to fulfil the requirement of imminent infringement.

In the case of a medical product, which has been authorised more than a year before the term of the patent but which has not been brought on to the market since then, the Higher Regional Court of Düsseldorf found that the grant of the authorisation was generally not sufficient to show that infringement was imminent. Thus, the court rejected imminent infringement, provided that the authorisation would not be withdrawn if it were not used until the end of the patent term.

The German Patent Act provides for an experimental use exemption and in particular also for the "Roche-Bolar" exemption, which allows the generic entrant to proceed with the application for marketing authorisation before the expiry of the patent. The exemption covers all actions which are necessary in order to receive the marketing authorisation.

Furthermore, there is a (theoretical) option for compulsory licences based on Section 24 of the German Patent Act. Even though this option is not strictly limited to pharmaceuticals or medical devices, the only case in which such a compulsory licence has been granted by the Federal Patent Court (upheld by the Federal Court of Justice) was related to a pharmaceutical product (an anti-retroviral HIV/AIDS medicament called "Isentress"). The interested licensee must apply for the grant of the compulsory licence and demonstrate:

  • that he or she failed to receive a licence in compliance with reasonable and common business practices after having tried to receive that licence over a reasonable period of time; and
  • that the public interest requires the granting of a compulsory licence.

Especially with regard to the current pandemic, it is worth noting that the Patent Act provides for the option that a patent shall have no effect in as far as the Federal Government orders that the invention is to be used in the interest of public welfare.

Typically, the patent-holder and the exclusive licensee can bring proceedings for patent infringement. The action can include claims for injunctive relief, rendering of accounts, recall and destruction of infringing products as well as damages.

The typical procedure starts at one of the most commonly used regional courts for patent litigation, which are Düsseldorf, Mannheim and Munich. The first-instance decision, which is provisionally enforceable, will be reached after eight to 15 months, depending on the court. This decision can be appealed before the Higher Regional Court.

These actions can be requested as preliminary measures, in which case the courts would generally require that the patent in suit has survived an inter partes validity attack. However, this requirement is often not applied to preliminary measures against generic entrants, thus preliminary injunctions can be granted. Only recently, the regional court of Munich has submitted a request for a preliminary ruling to the CJEU, asking whether the general requirement of inter partes validity proceedings in order to grant a preliminary injunction is compliant with the IP Enforcement Directive.

Since Germany has a bifurcated patent system, invalidity is not available as a defence in infringement proceedings on the merits. The alleged infringer must bring a separate nullity action before the Federal Patent Court to invalidate the patent. However, this nullity action usually takes more than two years, so that there is a so-called "injunction gap" between the (provisionally) enforceable infringement decision containing injunctive relief and the potential declaration of nullity of the patent in suit.

Even though German courts generally tend to be strict when granting preliminary injunctions if the patent has not been confirmed in inter partes validity proceedings, they often make an exception for cases against generic entrants. Therefore, if a generic entrant wishes to enter the market before the expiry of the originator's patent, he or she could file a nullity action before the Federal Patent Court in order to make sure that the potentially infringed patent will be invalidated before market entry. However, this option is very expensive and time-consuming.

There is no patent linkage system in place. Patent law and the laws governing the marketing authorisation of a generic drug are separate in Germany.

Other than using patent law, an IP rights-holder can take action against counterfeit pharmaceuticals and medical devices primarily based on trade-mark law:

Trade-mark infringement grants the rights-holder various remedies, including claims against the counterfeiter to cease and desist infringing the trade-mark, claims for damages and siphoning off the profits, and claims for destruction of the infringing products. In order to prevent counterfeit medicines from being imported, the rights-holder can also under EU Regulation (EU) No 608/2013 request the customs authorities to detain products suspected of infringing the holder's trade marks for further determination. Furthermore, trade-mark infringement can be criminally sanctioned and expose the counterfeiter to imprisonment of up to three years or monetary fines.

Pharmaceuticals and medical devices may not use names which are misleading, particularly regarding the efficacy and safety of the product (Section 8 of the  German Drug Act (Arzneimittelgesetz) (AMG), Section 4 of the Medical Devices Act (Medizinproduktegesetz) (MPG). Similarly, the EU MDR and IVDR prohibit in their Article 7 the use of any trade mark, name or text in the labelling, instructions claims, marketing and promotion which may mislead the patient regarding the device's intended purpose, safety or performance.

Specifically for pharmaceuticals, the regulatory authorities have issued guidelines on the acceptability of names or human medicinal products. For pharmaceuticals to be authorised centrally by the EU Commission, the guideline by the EMA applies. For pharmaceuticals to be approved nationally, the guideline by the BfArM and the PEI applies. Both guidelines set out further requirements and recommendations for developing an invented name for the pharmaceutical. The German guideline also addresses under which conditions one brand name can be used as an umbrella brand for several products of a product family.

The trade dress and design of pharmaceuticals, medical devices and their packaging may be protected by design rights and by copyright, potentially also by trade marks. This protection will depend on whether the trade dress or design in question meets the criteria for such protection. Registering design rights may present a relatively inexpensive way to protect the design of pharmaceuticals and particularly medical devices. Furthermore, the Act against Unfair Trade Practices (UWG) may afford the product-owner claims against competitors which pass off their products as the original products.

For pharmaceuticals, the data provided by the MAH in support of the MA application is protected by regulatory data exclusivity for eight years following the granting of the MA. For this eight-year period, other applicants may not cross-refer to the original clinical and pre-clinical data in support of an MA application for a generic copy of the pharmaceutical.

Furthermore, a generic product for which a MA has been granted through reference to the originator MA data may only be placed on the market after ten years following the granting of the original MA. If, during the first eight years, a new therapeutic indication has been added to the original MA which brings a major clinical advantage in comparison to existing therapies, the marketing exclusivity can be extended by up to one more year to eleven years (so-called "8+2+1" rule). These rules apply equally to chemical drugs and biologics.

For medical devices, no data-exclusivity rules apply because medical devices do not require an MA.

The BfArM has been granted authority to grant exemptions from various requirements of German drug law. This includes, where necessary, granting permissions to distribute medicines (i) with non-compliant labelling, (ii) which have been manufactured not in full compliance with GMP, or (iii) which are past their expiry date, granting exemptions from requirements applicable to clinical trials, MA applications, import of medicines, and compassionate-use programmes.

With respect to medical devices, based on the Commission Recommendation 2020/403, special temporary regimes have been in place until late summer 2020 allowing for the placing on the market of face masks which are not CE-marked, and enforcement against non-compliant face masks has been limited to those presenting a health hazard. Since face masks are no longer in short supply, regulatory enforcement against non-CE-marked face masks has increased.

The EMA has issued guidance on the management of clinical trials during the pandemic, to which the BfArM has issued complementing guidance. The EMA guidance provides that, subject to a number of specific circumstances, patients participating in clinical trials may exceptionally have investigational medicines delivered to their homes, with that delivery to be carried out by the trial sites or hospital pharmacies, or exceptionally through distributors.

Importers and manufacturers of face masks have requested of the BfArM in 2020 to be exempted from performing a full conformity assessment for non-CE-marked imported masks under Section 11 MPG (see Article 59 of the EU MDR), and to rely on a fast-track assessment by certain notified bodies. Since face masks are no longer in short supply, this pathway appears to be used less.

Generally, GMP certificates for manufacturing and importing sites in the EEA have been automatically extended until the end of 2021. Inspections are carried out remotely/virtually if needed.

In late February/March 2020, the German government temporarily banned the further export of protective masks. Subsequently, the enforcement of the regulations applicable to face masks imported into the EU and Germany was temporarily halted, but resumed since (see 11.1 Special Regulation for Commercialisation or Distribution of Medicines and Medical Devices).

The German healthcare system is undergoing a concerted digitalisation effort, including the wider use of telemedicine, which had been initiated before and independently of COVID-19. According to public polls, however, COVID-19 has sparked both more doctors to provide, and more patients to use, telemedicine services.

The German government has not announced any intention to issue compulsory licences for COVID-19-related treatments or vaccines.

No liability exemptions have been introduced for COVID-19-vaccines or treatments.

No manufacturing sites in Germany have been requisitioned or converted due to COVID-19.

The general rules governing public procurement have not been changed due to COVID-19. Based on the Protection against Infections Diseases Act (IfSG), the federal government can promulgate regulations allowing the government to take measures inter alia for procuring and stockpiling drugs and other necessary products. A number of tenders suggest that public purchases are increasingly placing stronger emphasis on more local manufacture and supply-chain resilience.

Baker McKenzie

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martin.altschwager@bakermckenzie.com www.bakermckenzie.com/en/people/a/altschwager-martin
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Law and Practice in Germany

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Baker McKenzie was founded in 1949 and is one of the world’s largest and most effective law firms, with more than 12,000 employees across 77 offices. The German offices seek to play their part in fulfilling the global vision of the firm’s two founders – Russell Baker and John McKenzie. Over 200 lawyers, spread across Berlin, Dusseldorf, Frankfurt/Main and Munich, can represent clients' interests, not only in Germany, but also beyond its borders, combining comprehensive expertise with long-standing experience. As one of Germany’s leading law firms, Baker McKenzie advises national and international companies and institutions on all aspects of commercial and tax law. In so doing, the firm concentrates on understanding the economic background to the work, while remaining focused on helping clients realise their business goals.