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.

Background

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.

Continue Reading EMA Guidance on Comparability Exercise for ATMPs

You will be aware from previous posts that industry has been concerned for some time about the amount of work to be done to ensure compliance with the Medical Devices Regulation (MDR), and whether this can be completed by May 2020, the date of application of the Regulation. However, so far, the Commission’s response has been that the current deadline is “realistic and achievable” and that there were no plans to delay implementation.

This week, as an early Christmas present to industry, while there is no delay to the data of application of the MDR, there is some good news: a “corrigendum”, or correction, to the MDR, has been approved by the Parliament that adds certain Class I devices to those devices that benefit from the transitional period under the MDR. This will give manufacturers of certain Class I devices additional time to comply with the Regulations.

Continue Reading Delays to the EU Medical Devices Regulations

This is a follow up to our previous posts relating to the European Medicines Agency’s (EMA) various policies on access to documents. This continues to be an area of activity for the EMA and there have been a number of developments that have impacted the EMA’s position. Firstly, Brexit has directly affected one of the main pillars of the transparency activities of the EMA, namely the proactive publication of clinical trial data submitted by pharmaceutical companies in support of certain types of regulatory submissions to the Agency (the EMA’s Policy 0070).

Secondly, while the reactive transparency activities of the EMA relating to access to documents in accordance with Regulation (EC) No 1049/2001 (the EMA’s Policy 0043) have been less affected by Brexit, there may be other challenges for the EMA ahead.

Continue Reading Latest Developments in the Transparency Activities of the European Medicines Agency

EU law places strict controls on the use of nutrition and health claims on food labelling and in advertising. Under Regulation (EC) No 1924/2006 (the Regulation):

  • a nutrition claim is any claim which states, suggests or implies that a food has particular beneficial nutritional properties due to the energy and/or nutrients or other substances it provides or contains (e.g., “low fat” or “source of fibre”); and
  • a health claim is one which states, suggests or implies that a relationship exists between a food category, a food or one of its constituents and health (e.g., “Calcium is needed for the maintenance of normal teeth”).

Under the Regulation, it is only possible to use nutrition claims that are listed in the Annex to the Regulation, and/or health claims that have been authorised by the European Commission following a European Food Safety Authority scientific review. The only exception to these requirements is in relation to claims that are trade marks (or brand or “fancy” names) and general, non-specific health claims (e.g., “Good for you” or “Healthy”). These claims may be used without prior approval, provided they are accompanied by an approved claim (which, in the case of a general health claim, must be an authorised specific health claim, such as the calcium example given above).

Continue Reading Latest View on Health Claims on Foods in the EU

Earlier this month, the European Commission and representatives of the EU Member States discussed potential revisions to the European Commission’s Note on handling of duplicate marketing authorisation applications (the 2011 Note). According to the information published by the Commission, the discussion took place on 7 November 2019 during the latest Pharmaceutical Committee meeting. The discussion was intended to be focussed on duplicate marketing authorisations for biological medicinal products and the outcome of the related public consultation that took place in 2018.

Background

As we set out in our previous blog, the 2011 Note provides guidance on how the European Commission handles requests for duplicate marketing authorisations submitted through the centralised marketing authorisation procedure in accordance with Article 82.1 of Regulation (EC) No 726/2004 which was motivated by concerns that several MA’s granted for the same product could lead to partitioning of the market. As a general principle, the Regulation contemplates the existence of duplicate marketing authorisations only in two situations; first, where co-marketing with an independent company is envisaged and secondly “where there are objective verifiable reasons relating to public health regarding the availability of medicinal products to health-care professionals and/or patients”. In this latter case the Commission has required the applicant to demonstrate that the grant of a duplicate marketing authorisation will result in improved availability of the medicinal product in the EU. The 2011 Note states that, in principle, the grant on “public health” grounds of a duplicate marketing authorisation for a “first generic” granted to an originator (known as an “authorised generic” in the USA) is possible because of its potentially positive impact on the availability of the medicinal product.

Continue Reading Update on EU Duplicate Marketing Authorisations

On 16 October 2019, the European Commission published the Guidelines for Good Clinical Practice (GCP) specific to advanced therapy medicinal products (ATMPS) covering gene therapies, cell therapies and tissue engineered products. These Guidelines are available at the website of the European Commission.

Background

The European Commission was legally required to adopt the GCP Guidelines specific to ATMPs (the Guidelines) by Regulation (EC) No 1394/2007 (ATMP Regulation) with the technical input from the European Medicines Agency (EMA). The Guidelines were adopted after a period of public consultation with the targeted stakeholder consultation in the second half of 2018.

The Guidelines reflect the experience gained by the European Commission and the EMA in the field of ATMPs and in the assessment and authorisation of this type of medicinal products. Due to their complex nature, ATMPs present specific practical operational and regulatory challenges related to GCP compliance.

Continue Reading Latest Updates on Good Clinical Practice for Advanced Therapies in the EU

A recent CJEU judgment serves as a useful reminder to pharmaceutical companies of the dangers of registering a trade mark prematurely in the development of pharmaceutical products.

Background of the case

On 28 November 2017, Viridis Pharmaceutical Ltd brought an appeal before the CJEU against the General Court’s verdict to uphold the EUIPO’s Board of Appeal decision to revoke Viridis’s BOSWELAN trade mark for pharmaceutical products. The trade mark was originally revoked by the EUIPO following a claim by Hecht-Pharma GmbH that Viridis’s trade mark had not been put to ‘genuine use’.

Viridis appealed the General Court’s decision before the CJEU on the following grounds:

  1. The BOSWELAN trade mark had been put to ‘genuine use’ during the course of clinical trials; and
  2. There was a ‘proper reason’ for non-use of the trade mark which was sufficient for the purposes of avoiding revocation of the mark.

Continue Reading Pharmaceutical companies: beware of revocation of EU trade marks for lack of ‘genuine use’ during clinical trials

On 6 September 2019, Regulation (EU) 2019/1381 of the European Parliament and of the Council on the transparency and sustainability of the EU risk assessment in the food chain (the “Regulation”) was published in the Official Journal of the European Union.

Review of the matters addressed by the Regulation was initially prompted by a European Citizens’ Initiative (#StopGlyphosate), which campaigns against the use of toxic pesticides and for reform of the EU pesticides approval procedure.

The new Regulation principally amends Regulation (EC) No 178/2002 laying down the general principles and requirements of food law (the “General Food Law Regulation”). It also amends eight sector-specific legislative acts, concerning genetically modified organisms, feed additives, smoke flavourings, food contact materials, food additives, food enzymes and flavourings, plant protection products and novel foods.

Continue Reading Strengthened Transparency in the EU General Food Law Regulation

We recently published an Advisory on a decision of the CJEU earlier this month on parallel trade. Ordinarily, medicinal products can only be placed on the EU market if they have a valid marketing authorisation in the relevant Member State. However, within the EEA, the principle of free movement of goods applies, meaning that, subject to certain exceptions, Member States cannot prevent free movement of goods once they are lawfully on the market. Therefore, once a product has lawfully been placed on the market, it is possible for third parties to move that product between Member States, subject to certain requirements. This is known as parallel trade.

There have been many decisions in the CJEU considering when medicinal products can be parallel traded across the EU, and the limits on such trade. This recent decision from Poland (Case C-387/18, Delfarma), is the latest in this line of case law.

Continue Reading Recent Important Decisions on Regulatory Requirements for Parallel Trade in the EU

RoHS refers to Directive 2011/65/EU on the restriction of the use of certain hazardous substances in electrical and electronic equipment (EEE). It is illegal to place EEE products on the market that are non-compliant with RoHS, and doing so risks criminal prosecution, with potentially unlimited fines on conviction.

The original RoHS legislation was made in 2003. Under RoHS, EEE must not contain the restricted substances, which comprised lead, cadmium, mercury, hexavalent chromium, polybrominated biphenyls (PBB) and polybrominated diphenyl ethers (PBDE). Only trace amounts, no higher than the specified “maximum concentration value by weight in homogeneous materials” may be tolerated. There are also exemptions for certain uses.

Now, Directive 2015/863, which updates RoHS, has added four phthalates (chemicals typically used to soften plastic) to the restricted list from 22 July 2019: butyl benzyl phthalate (BBP), di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and diisobutyl phthalate (DIBP).

Continue Reading RoHS: EU Phthalate Restrictions in Electrical and Electronic Equipment