Marketing authorisation and clinical testing of new drugs

Facilitation of clinical trials and access to marketing authorisation during the COVID-19 pandemic

In the fight against the COVID-19 pandemic, reports of potentially promising treatment options are reported almost daily. Everybody gets informed that numerous vaccine candidates against the corona virus are being developed worldwide or may even soon be available. In addition, already known drugs and agents are used for the treatment of people suffering from Sars-Cov-2 that do currently neither have marketing authorization for this indication, nor has sufficient proof of efficacy yet been collected due to the short duration of the pandemic. The Ebola drug "Remdesivir", the malaria drug Hydroxychloroquine and the HIV drug Kaletra (combination of ritonavir and lopinavir) are said to be among the most promising candidates at present, and various clinical trials are underway worldwide.

Clinical trials and current limitations on feasibility

Notwithstanding these measures to combat the current pandemic and its urgency, it must also be ensured that the "normal" course of clinical trials for active substances against other diseases is not completely suspended. The need for effective treatments for other diseases will continue to exist in the post-Corona period. Ongoing clinical trials, however, currently have to struggle with considerable hurdles due to the general restrictions of public life. Contact bans on the one hand and the strict requirements of uniform procedures for clinical trials on the other hand are currently in considerable diametric contradiction.  

Clinical trials for new uses and the patent law experimental privilege

Insofar as the use of already known active substances such as Kaletra, Remdesivir or Hydroxychloroquine, which are already patent-protected as such, is discussed in clinical trials, the basic idea of German patent law applies that the use of active substances that are patent-protected should not constitute a patent infringement if it is used for "experimental purposes".

This so-called "experimental privilege" is regulated in the provision of Sec. 11 No. 2 German Patent Act and has led to some particularly practice-relevant decisions of the German courts.  

In particular, the two cases "Clinical Trials I" and "Clinical Trials II", decided by the Federal Court of Justice (BGH) in the late 1990s, that had a decisive influence on the understanding of the exemption, are of importance here.

In the decision Clinical Trials I (BGH, 11 July 1995, Ref. X ZR 99/92) it was stated that the German Patent Act allows all trials which serve to obtain information and thus to carry out a scientific purpose, including those which serve to discover the effects of a substance or possible new, previously unknown uses. It should be irrelevant whether the experiments serve to verify the statements made in the patent or to obtain further, more recent research results. In particular, the Federal Supreme Court held that it is irrelevant that the tests are carried out for the purpose of obtaining a marketing authorisation.

In the decision Clinical Trials II (Federal Supreme Court, April 17, 1997, file no. X ZR 68/94), the Federal Supreme Court decided that the experimental privilege of Sec. 11 no. 2 German Patent Act should also apply if and to the extent that the trials serve the purpose of researching the subject matter of the invention which is actually protected by patent. The exemption from otherwise applicable patent law provisions applies irrespective of any additional motives and purposes which the results might serve; they may range from purely scientific experiments to concrete commercially indicated experiments.

Similar to other European legal systems (e.g. UK), however, the use of research tools and the performance of bioequivalence tests is not exempted, as these measures do not provide new insights into the subject matter of an invention. Purely commercial purposes, such as the use of the invention in market surveys, for example to determine whether there might be a commercial demand, are also not exempted.

Patent freedom for tests and studies to obtain marketing authorisation ("Bolar rule")

For the purpose of European harmonisation of an experimental privilege, in particular for the purpose of obtaining marketing authorisations for medicinal products, the so-called "Bolar rule" was introduced in Sec. 11 No. 2b German Patent Act in 2005. According to this provision, the effect of a patent does not extend to studies and tests and the resulting practical requirements that are necessary to obtain a marketing authorization for medicinal products in the European Union or a marketing authorization for medicinal products in the member states of the European Union or in third countries.

This wording as such is relatively broad and does not distinguish, for example, whether the authorisation should be granted to generic or innovative medicines. The provision also covers studies and trials necessary to obtain a marketing authorisation in the European Union and in third countries. The import of an active ingredient that was manufactured in a foreign country without a patent and imported into the patent protected domestic market for the purpose of carrying out trials to obtain a marketing authorisation also falls under the Bolar exception in the opinion of the Düsseldorf Higher Regional Court (5 December 2013, Case No. I-2 U 68/12). It justified its decision with the purpose of the Bolar exception, which is to enable the immediate market entry of generics and the strengthening of the generics industry in the EU from the time of the expiry of a patent protection. However, since the Bolar Directive is based on EU law and the referral decision of the OLG Düsseldorf to the European Court of Justice as unfortunately not been decided, there is still a certain degree of uncertainty as to whether imports for trial or market approval purposes are permitted.

These regulations could become particularly relevant if - as is currently the case – already known, patent-protected active substances are used for the purpose of research into possible efficacy against the corona virus. It can be assumed that with an increasing chance of having found a candidate, the covetousness will also increase and may lead to legal discussions. Even before the product is ready for the market and any orders for use/compulsory licenses are issued, the experimental privilege and the Bolar rule could be "used" here.

Clinical trials during the COVID-19 pandemic

Irrespective of patent law issues, the current restrictions also lead to various legal uncertainties in ongoing clinical trials. The European Medicines Agency (EMA) and the German Federal Institute for Drugs and Medical Devices (BfArM) have recognised this and published corresponding proposals for the adaptation of the problematic regulations in particular. Apart from stating that it is questionable whether any clinical trials that have not yet started should be postponed if necessary and whether ongoing studies should be interrupted, the guidelines particularly concern the following aspects of clinical trials:

• Remote monitoring of clinical trials and shipment of investigational medicinal products in lieu of personal appearance of trial subjects, where this is compatible with national data protection.

• Revision of existing study designs, insofar as the COVID-19 pandemic could have an impact (including any necessary change notifications and early contact with the competent authorities in case of uncertainties).

It is to be assumed that the data protection regulations in particular, but also the implications in terms of licensing law, may lead to discussions in the medium term, but these should be avoided now if possible.

Current information on clinical trials in the context of COVID 19 can be found on the BfArM website. 

We have compiled on our website comprehensive information and recommendations for action in response to the legal implications arising from the coronavirus pandemic: Coronavirus - legal issues