The EMA and the competent authorities of the EU Member States have issued guidance to manage the conduct of clinical trials and the supply of medicinal products during the COVID-19 pandemic. This Guidance is particularly important for all sponsors conducting studies in the EU and for pharmaceutical companies supplying medicines in the EU. We discuss the key elements and practical implications for the concerned pharmaceutical companies in our recent advisory.
With only two months to go before the date of application of the Medical Devices Regulation (MDR) on 26 May 2020, the Commission has taken various steps towards its implementation. As we have discussed, while there are lots of good intentions, there is still much to be done – although it now seems that a delay to the May date is on the horizon.
Last week, the MDCG published a number of guidance documents providing much needed clarity on some of the “priority” areas. These are set out below, with particular comments on the guidance relevant to the transitional provisions under the MDR.
As set out in our previous post, it is two months until the (current) date of application of the Medical Devices Regulation (MDR) on 26 May 2020. In this series of posts, we wanted to update you on the state of implementation given the fast-approaching deadline. However, as we were speculating that the current timeframe was looking increasingly untenable, the Commission announced yesterday (25 March) that it was working on a proposal to postpone the date of application by a year. This is intended to allow national authorities and industry to focus on responding to the coronavirus crisis.
The statement notes that “The Commission is working to submit this proposal in early April for the Parliament and the Council to adopt it quickly as the date of application is the end of May.” It has also been reported that the Parliament is receptive to such a proposal, and is aware of the tight timeline.
While we don’t yet know what the terms of the proposal will be, or how it will operate with all the various transitional provisions within the MDR, it will be welcome news to the industry, which is already under pressure due to the new provisions under the MDR, and now the coronavirus pandemic. We will keep you updated as more information is published.
There are now only two months to go before the date of application of the Medical Devices Regulation (MDR) on 26 May 2020. We have previously published updates on various implementation activities, and the concerns of industry and stakeholders that the deadline has been fast approaching but that there remains a huge amount to be finalised. The difficulties surrounding Brexit, and now the coronavirus pandemic, only add to these concerns. With the short amount of time remaining, we set out in this series of posts a summary of recent key developments.
As expected, the recent activity is focused on the MDR, and does not, on the whole, address the In Vitro Diagnostics Regulation (IVDR), which is due to be applicable in 2022. While this is a pragmatic approach from the institutions given current timing, it remains the case that IVD manufacturers have little clarity on how the IVDR will operate, and it seems, are unlikely to obtain any in the near future.
The Neurim CJEU decision of July 2012 has arguably caused an equal amount of excitement and controversy. On the one hand, it seemed to open the door to supplementary protection certificates (SPCs) for second or further medical uses. On the other, it seemed to go against a number of previous decisions. On a strict literal interpretation of Article 3(d) of the SPC Regulation, it should not be possible to obtain an SPC for new applications of old active ingredients that had already been the subject of a marketing authorisation. In Neurim, based on a teleological interpretation to the SPC Regulation, the CJEU held that such an SPC could be validly granted.
A recent Opinion from Advocate General M. Giovanni Pitruzzella in the Santen SPC preliminary reference urges the CJEU to expressly reject the Neurim decision, considering that the mere limitation of its application or marginalisation would not be a satisfactory option.
The facts in Santen
On 3 June 2015, Santen filed an SPC application relying on European Patent No. 057959306 as the basic patent in force (the “basic patent”) and on an EMA marketing authorisation granted on 19 March 2015 for the drug Ikervis (an eye drop emulsion containing the active ingredient ciclosporin used to treat severe keratisis). The French National Institute of Industrial Property (“INPI”) rejected the application on the ground that a marketing authorisation had been previously issued for the same active ingredient for a medication called Sandimmun (an oral solution with several therapeutic indications including the eye disease uveitis, an inflammation of some or all of the uvea (the middle part of the eye)).
INPI held that the conditions in Neurim had not been satisfied for two reasons:
- the basic patent was not limited to the severe keratisis indication – the claims included product only claims and claims to numerous other eye diseases; and
- Santen had not demonstrated that the marketing authorisation constituted a ‘new therapeutic indication’ within the meaning of Neurim (for example, where the mode of action of the active ingredient differs or where the medical field differs).
Santen appealed the decision to the Paris Court of Appeal and it, in turn, decided to stay proceedings referring two preliminary questions to the CJEU. The first question has asked the CJEU to consider how the concept of “different application” of an old active substance as understood in Neurim should be interpreted and the question provides a range of possible options from strict to broad interpretations. The second question asks whether, in the context of determining whether the “[SPC application is] within the limits of the protection conferred by the basic patent” as understood in Neurim, the scope of the basic patent should be the same as the marking authorisation relied upon (i.e. it should be limited to the new medical use corresponding to the therapeutic indication of that marketing authorisation).
Less than six months after the preliminary reference was made by the Paris Court of Appeal, the CJEU had the opportunity to consider the scope and relevance of the Neurim decision in the Abraxis SPC case. In that case the CJEU did not openly criticise the Neurim decision and, instead, limited its ramifications by referring to it as an “exception to the narrow interpretation of Article 3(d)” which “does not, in any event, refer to cases of new formulations of the product at issue”.
Opinion of the CJEU Advocate-General in Case C-581/18 RB v TÜV Rheinland LGA Products GmbH, Allianz IAED SA: application of the principle of non-discrimination on grounds of nationality in a medical device case.
The effects of the Poly Implant Prothèse SA (PIP) defective breast implant scandal continue to be felt almost ten years since it first came to light that PIP had fraudulently used cheaper, industrial grade silicone in the implants that it manufactured. Due to PIP’s insolvency, those affected have attempted to obtain compensation from other sources, including the relevant notified body, TÜV Rheinland, on the basis that this body had negligently certified PIP’s products and the French regulatory authorities.
Case against PIP’s insurer
The Opinion of Advocate-General Bobek in Case C-581/18 RB v TÜV Rheinland LGA Products GmbH, Allianz IARD SA concerns a German claimant (RB) who pursued a case for compensation in respect of defective breast implants in Germany against Allianz, the insurers of the now-defunct PIP in France. Medical device manufacturers were required under French law to have insurance cover for harm suffered by third parties arising from their activities. PIP had a policy of cover with Allianz, but the cover was limited to damage caused in France. Allianz relied on that territorial limitation. RB maintained that the territorial limitation of insurance cover to French territory was not lawful and constituted an infringement of free movement of goods.
The German court referred the case to the Court of Justice of the European Union (CJEU), asking whether the territorial limitation in the Allianz insurance policy constituted a violation of Article 18 TFEU, which prohibits discrimination on the grounds of nationality.
Within the scope of EU law
Allianz and the French government argued that the case fell outside the scope of EU law on the basis that the issues involved a German patient who underwent surgery in Germany and were therefore purely internal to Germany. The Commission seemingly adopted a similar view.
Advocate-General Bobek disagrees, concluding that it is not possible to say that the situation in the present case falls outside the scope of EU law as it involved the cross-border movement of goods (PIP implants) and provision of services (insurance) in the context of the partial harmonisation of medical devices and liability for defective products under EU law.
The UK government published its Medicines and Medical Devices Bill (the Bill) on 13 February 2020. The Bill seeks to introduce delegated powers which will allow the Secretary of State to amend or supplement the existing UK regulatory framework for medicines, medical devices, clinical trials and veterinary medicines at the end of the transition period for the UK’s departure from the EU (the Transition Period), which is currently scheduled for 31 December 2020. The Bill also consolidates and expands on the existing UK medical devices enforcement powers and provides for an information gateway to permit sharing of information held by the Secretary of State in relation to medical devices.
Yesterday, the Food Standards Agency (FSA), which regulates foods and food businesses in England, Wales and Northern Ireland, issued its long-awaited statement on CBD in foods.
In January 2019, the European Commission updated the Novel Food Catalogue to state that extracts of Cannabis sativa L. and derived products containing cannabinoids are considered as novel foods, as a history of consumption has not been demonstrated. As a result, all extracts of hemp and derived products containing cannabinoids (including CBD) are now regarded by the European Commission as novel. The FSA responded by stating that it accepted the conclusion of the Commission and was “committed to finding a proportionate way forward…to clarify how to achieve compliance in the marketplace in a proportionate manner”.
Following the UK’s departure from the European Union, the current rules on novel foods will continue to apply until 1 January 2021, when the transition period under the UK’s withdrawal agreement from the EU comes to an end. However, the FSA has now confirmed its position on enforcement and prescribed actions which it considers “are a pragmatic and proportionate step in balancing the protection of public health with consumer choice“.
Advocate General Kokott issued her opinion last week in the preliminary ruling referral from the UK Competition Appeal Tribunal (CAT). The CAT proceeding is itself an appeal against an infringement finding against a number of companies (except one, IVAX, which is now part of TEVA, which received a ‘No Grounds for Action’ letter).
AG Kokott finds that an agreement to settle a patent dispute may constitute a restriction of competition by object or by effect and that entering into such an agreement may be an abuse of a dominant position. This is in line with the General Court’s recent judgments in Perindopril and Lundbeck, but her views diverge on market definition where she seems to side with the CAT on a narrow, molecule-level definition.
On 13 December 2019, the European Medicines Agency (“EMA”) published a Questions and Answers document (“Q&A”) providing guidance on the conduct of comparability exercise for advanced therapy medicinal products (“ATMPs”). The Q&A addresses various regulatory questions that arise in situations in which companies developing or marketing ATMPs introduce changes to the manufacturing process and need to generate related comparability data.
EMA’s experience suggests that changes to the manufacturing of ATMPs are “frequent” and even more so in the development of the medicinal product. These changes need, however, to be introduced in accordance with the Good Manufacturing Practices (“GMP”). Moreover, the changes may require a variation of the marketing authorisation for authorised ATMPs or substantial amendments to the clinical trial protocol for ATMPs used in clinical trials.
In addition, the changes to the manufacturing of the ATMP must be supported by the data generated in a comparability exercise. This exercise should focus on the characteristics of the ATMP prior and after the introduction of the manufacturing change. This is valid for both investigational ATMPs and authorised ATMPs.
The position of the EMA is that changes to the manufacturing of the ATMP should not undermine or impact adversely the quality, efficacy or safety of the medicinal product or the related risk-benefit balance. The objective of the comparability exercise is to facilitate the assessment and demonstration of this.