Regulatory news - January 2018

Keep up to date with regulatory news from around the world with the Cell and Gene Therapy Catapult regulatory newsletter.


European Commission (EC)

New repository containing national GMO requirements for investigational medicines

For particular advanced therapy medicinal products (ATMPs) in the European Union (EU) which involve genetic modification (in vivo or ex vivo) consideration must be given to legislation for Genetically Modified Organisms (GMOs) in addition to Clinical Trial Authorisation (CTA).

Unlike the relatively harmonsied CTA approval producedure across the EU, GMO notification has until recently been a relatively infrequent consideration for developers of medicinal products. This has led varied interepretation and implementation of the law in each member state affecting how, what, when and to whom to submit as well as the scope of an approval in relation to a clinical trial.

Addressing this European hurdle has been on the EC’s agenda for some time. To help developers, the EC has initially published a new repository with an overview of the key national requirements within Europe. Importantly, the EC has highlighted that these new documents are for information; the legal responsibility for oversight and approval remains with the relevant competent authoritiy.

Click here to access to the repository.

European Medicines Agency (EMA)

Ten-year report on conditional marketing authorisation (CMA)

The Conditional Marketing Authorisation (CMA) was introduced to support early access to medicines that address unmet medical needs of patients in the European Union (EU). It allows for the initial authorisation of medicines if the public health benefit of their immediate availability to patients outweighs the risk (i.e. in seriously debilitiating/life-threatening diseases, medicinal products for use in emergency situations and orphan medicines). The holder is required to complete specific obligations e.g. new studies to obtain complete data to confirm that the benefit-risk balance is positive. The EMA Committee for Medicinal Products for Human Use (CHMP) review the data collected annually and decide about a further renewal of the CMA or its conversion into a standard marketing authorisation.

The report analyses a total of 30 medicines authorised under CMA over 10 years between 2006 and June 2016. The majority (24/30) were for seriously debilitating or life-threatening conditions and 14/30 medicines were orphan indications (14/30). Only 3 products were classified under emergency situations; all for influenza pandemic vaccines. CMAs have been granted for the following therapeutic areas: oncology (17/30), infectious diseases (9/30), neurology (3/30) and ophthalmology (1/30).

The report provides various analyses about successful CMAs including general characteristics, compliance with scientific advice in terms of primary endpoint, comparator and statistical methods, type of data submitted at time of CMA and the characteristics of the specific obligations. The report includes also an analysis of unsuccessful CMAs; the majority of which have been attributed to a negative benefit/risk balance related to ‘methodological, GCP and/or statistical issues mak[ing] data unreliable

The report recognises the success of this regulatory tool. On average, a CMA is converted into a standard marketing authorisation within 4 years. EMA recommends an early dialogue with agency and prospective planning of CMAs to prompt assessment, completion of additional studies and availability of comprehensive data.

Figure 1: status of conditional marketing authorisation by year of authorisation

Extracted from the Conditional marketing authorisation report on ten years of experience at the European Medicines Agency, January 2018

Click here to access to the EMA report in full.

ATMP: Streamlined evaluation process; updated safety and efficacy follow-up and risk management guideline

In October 2017, EMA and EC published a joint action plan to improve the regulatory framework for advanced therapy medicinal products (ATMPs). The objectives are to increase the opportunity for EU patients to be treated with novel innovative therapies and to address the specific bottlenecks for ATMP development.

In accordance with this plan, EMA released this month

  • an update to the procedural advice on the evaluation of ATMPs,
  • a draft revised guideline on safety and efficacy follow up and risk management of ATMPs.

Updated ATMP evaluation process guideline

The document describes the evaluation process and review timetable for ATMPs, as well as the roles and responsibilities of the various rapporteurs and committees involved in the assessments.

Essentially, the new approval process:

  1. Streamlines some procedural aspects:
    1. Same processes for adopting ‘Day 120’ and ‘Day 180’ questions during the evaluation will apply
    2. Simplification of the process for oral explanation at committees
  2. Strengthens collaboration between EMA’s scientific committees. Two assessment teams are appointed from the different EMA committee as follows:

A representant of each committee during discussion will ensure a consistent flow of information and facilitate discussions between committees.

  1. Describes the role of the Committee for Pharmacovigilance and Risk Management (PRAC) in the assessment of the ATMPs. A PRAC rapporteur is also appointed from amongst the members and alternates of the PRAC.
  2. Reflects current practice of providing ATMP developers with the possibility of longer periods (‘clock-stops’) to respond to questions raised during evaluation

Click here to access to the guideline in full, here for the EMA presentation

ATMP safety and efficacy follow-up and risk management guideline

Due to the novelty, complexity and technical specificity of ATMPs, these products need to be managed through the risk management plan. This revised draft guideline is currently in public consultation until 30 April 2018. The document reflects EMA’s experience gained with the authorisation of these medicines, as well as the experience with scientific advice and protocol assistance.

Figure 2: Schematic overview of the risk based approach

The rules described in this guideline are developed to facilitate risk detection of particular ATMP risks and provide a framework for effective mitigation of their impact to patients (e.g. educational programme). The guideline also provides methodological advice on design of appropriate post-authorisation studies to follow up on the safety and efficacy of these medicines.

Click here to access to the guideline in full.

Orphan maintenance assessment report to be published

As part of a medicine’s European Public Assessment Report (EPAR), an orphan maintenance assessment report will now be published for every orphan-designated medicine which has been recommended for marketing authorisation. This new report addresses stakeholder requests for increased transparency with regards to decision-making for orphan medicines market exclusivity.

The new report will summarise the decision making process by the EMA Committee for Orphan Medicinal Products (COMP) on whether a medicine designated as an orphan medicine during its development still fulfils the designation criteria at the time of its authorisation. This confirmation will allow the license holder to benefit from ten-year market exclusivity, considered to be the biggest incentive of the European Union (EU) orphan programme.

In a statement, Bruno Sepodes, the Chair of COMP also highlighted that “health technology assessment bodies (HTAs) might use this additional information when establishing the cost effectiveness of the medicine”.

Click here to access to first orphan maintenance assessment report

Click here to access to EMA’s news

EMA survey on pharmaceutical manufacturer’s preparation for Brexit

The EMA is launching a survey for Marketing Authorisation (MA) holders of centrally authorised medicines regarding their plans to prepare for Brexit.

On its Brexit Q&A published in November 2017, EMA highlighted a future requirement that holders of centrally authorized medicines located in the EU will need to transferthis license to a legal entity in the EEA, ensure a Qualified Person for PharmacoVigilance (QPPV) is located in the EEA as well as ensure any SME is registered in the EEA (directly or indirectly) to continue benefiting from SME incentives.

With this survey, the EMA aims to

  1. identify companies where there is a need for concerted action to address medicines supply concerns due to Brexit
  2. plan resources in the areas where these submissions will be processed.

In the figure below, EMA captured the porportion of UK-based activities that will require action. The survey must be completed by 9 February 2018. Once complete, the EMA will publish a high-level summary of the overall results.

Figure 3: Key figures of ema survey (as of 10 January 2018)

Extracted from EMA's website

Click here to access to EMA press release

United Kingdom

Medicines and Healthcare products Regulatory Agency (MHRA)

MHRA reassured developers on pragmatic approach in the event of no ongoing relationship with EMA networks

In December 2017, the UK and EC agreed to advance Brexit negotiations to a second phase. An agreement has been reached that products placed on the market before the UK's withdrawal should be able to remain on the market in both jurisdictions without modification or re-labeling. EU acknowledged UK proposal for a time-limited implementation period, based on the existing structure of EU rules and regulations. Despite of these reassurance, the industry wanted MHRA to further detail what will happen in case of a ‘no-deal’ scenario with EMA. In January, the MHRA confirmed that “there would be no sudden changes to the UK regulatory framework”, and that a “pragmatic approach” in establishing UK regulatory requirements will be adopted and give adequate notice toensure companies have sufficient time to implement any changes . Both the Association of the British Pharmaceutical Industry (ABPI) and UK Bioindustry Association (BIA) welcomed the MHRA's statement

Click here to see MHRA’s statement in full

Public consultation on draft guidance on health institution exemptions under IVDR/MDR

In May 2017, new EU Regulations were published which include a specific exemption for in vitro diagnostic medical devices (IVDs) and medical devices (MDs) that are used in the same health institution as they are made or modified but with some specific requirements. According to Article 5(5) of both regulations, health institutions will need:

  • to ensure that products meet the relevant General Safety and Performance Requirements;
  • to have an appropriate quality system in place;
  • to have a justification for applying the exemption;
  • to have a technical documentation in place.

MHRA launched an extensive consultation (until 31st March 2019) on the draft guidance on health institution exemptions under IVDR/MDR. The draft includes sections on the transfer of devices, quality management systems, manufacturing, surveillance, governance, distance sales and control of subcontractor. The MHRA would appreciate help from a broad range of stakeholders in developing guidance and feedback on whether MHRA is taking the right approach to the regulation of devices.

Click here to access to MHRA draft guideline in full


Food and Drug Administration (FDA)

New gene therapy guidelines planned for 2018

FDA Center for Biologics Evaluation and Research (CDER) has issued an initial list of planned guidance topics for 2018. Several of these guidelines will be specifically designed for gene therapy products as detailed below:

  • Testing of Retroviral Vector-Based Gene Therapy Products for Replication Competent Retrovirus during Product Manufacture and Patient Follow-up; Draft Guidance for Industry
  • Observing Subjects Who Received Human Gene Therapy Products for Delayed Adverse Events; Draft Guidance for Industry
  • Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs); Draft Guidance for Industry
  • Gene Therapy for the Treatment of Hemophilia; Draft Guidance for Industry

Click here to view the CBER guidances.

FDA to increase transparency of clinical study reports

As part of FDA efforts to enhance transparency, a new (voluntary) pilot program has been launched to evaluate whether disclosing certain information included within Clinical Study Report (CSRs) following approval could improves public access to drug approval information. The EMA began taking similar steps in 2016.

Specifically, it will include the study report body, the protocol and amendments, and the statistical analysis plan for each pivotal study included. The pilot will select up to nine recently-approved new drug applications (NDAs) whose sponsors volunteer to participate.

Click here to access to the press release

Public consultations





Consultation period



Draft guidance on the health institution exemption (HIE) – IVDR and MDR

22 Jan 2018 to 31 Mar 2019

Draft guidance