Regulatory news - September 2018

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


European Medicines Agency (EMA)

Luxturna : CAT/CHMP recommends granting marketing authorisation

Spark Therapeutics’ Luxturna, approved by the US FDA at the end of 2017, has been recommended for marketing authorisation by the European Medicines Agency’s (EMA) Committee for Advanced Therapies (CAT) and the opinion adopted by the EMA’s Committee for Medicinal Products for Human Use (CHMP).

Luxturna is an adeno-associated virus gene therapy for the treatment of adults and children suffering from a rare genetic disorder knowns as inherited retinal dystrophy which is caused by RPE65 mutations, which causes vision loss and usually leads to blindness.

Luxturna delivers a functional RPE65 gene into the cells of the retina via a single injection. This gene encodes an enzyme in the retinal pigment epithelium (RPE) thereby improving the patient’s ability to detect light.

The safety and efficacy of Luxturna has been established in a total of 41 patients between the ages of 4 and 44 years. In the main clinical trial supporting the approval of Luxturna, patients treated with the medicine showed a significant improvement of night vision, one of the typical symptoms of the disease, after one year, while no improvement was seen in the control group.

Given the novel approach and the limited number of treated patients, follow-up studies which are required include:

  • a post-authorisation safety study (PASS) based on a disease registry in patients with vision loss due to inherited retinal dystrophy caused by confirmed biallelic RPE65 mutations
  • a 15-year follow-up program of efficacy and safety outcomes for all patients treated in the clinical program

The CHMP opinion will now be sent to the European Commission for legal adoption across the EU and EEA.

Click here to view EMA press release.

Click here to view Spark Therapeutics press release.

EMA highlights the use of Real World Data

In a recent article published in the American Society for Clinical Pharmacology and Therapeutics journal, the EMA together with relevant stakeholders have proposed improvements in the use of Real World Data (RWD) to support development and utitilisation of innovative pharmaceuticals.

As outlined in a recent report from the Organisation for Economic Co-operation and Development (OECD):

While all countries are investing in health data infrastructure, and electronic health records are now widely used, significant cross-country differences exist.

The paper outlines the growing demand for a ‘learning healthcare system’ that makes full use of RWD to complement evidence based on randomised controlled trials. RWD has the potential to substantially increase the effectiveness and efficiency of all processes in the development and utilisation of medicines including regulatory decision-making, pricing and reimbursement decisions if robust and reliable data from sources such as electronic health records can becollected on a consistent basis.

Ultimately, information collected this ‘real-world’ context, as opposed to data generated in a “research-setting” can be highly informative for a range of stakeholders, in allowing for a more robust understanding of the efficacy and safety risks of a particular medicine.

Click here to view the article in full

United Kingdom

MHRA/HRA allows electronic consent form for clinical trials

The Medicines and Healthcare products Regulatory Agency (MHRA) together with the Health Research Authority (HRA) (and endorsed by the UK health departments in Northern Ireland, Scotland and Wales) have published a joint statement on seeking and documenting consent using electronic methods (eConsent).

According to MHRA, eConsent offers a number of potential benefits such as improving understanding, testing and reinforcing participant comprehension, providing feedback on how consent materials could be improved, improving patient recruitment process and reducing dropout rates, enabling process efficiencies.

The statement sets out the legal and ethical requirements for eConsent. For Clinical Trials with Investigational Medicinal Products (CTIMPs), eSignatures that involve the participant tracing their handwritten signature using a finger or a stylus or biometric eSignatures should normally be used as they allow for direct comparison with eSignatures and/or wet-ink signatures previously used by the participant for the purpose of audit or where the consent is contested.

This electronic approach can supplement or replace the traditional paper-based approach where appropriate.

Click here to access to statement in full.

MHRA/BIA publishes the conference report on “Collaborative Working in the UK, Driving Innovation Forward

The UK BioIndustry Association (BIA) and the Medicines and Healthcare products Regulatory Agency (MHRA) have recently published a report from their 8th Annual joined Conference.

This conference reflects continued dialogue between the stakeholders involved in getting innovative medicines to patients in the UK such as the MHRA, the National Institute for Biological Standards and Control (NIBSC), the Clinical Practice Research Datalink (CPRD), the Department of Health and Social Care, the National Institute for Health and Care Excellence (NICE), the Office for Life Sciences, notified bodies, the life science industry, research charities and patient organisations.

The key topics discussed during the one-day conference included the current regulatory environment and perspectives post-Brexit, accelerated access pathway for breakthrough therapies and technologies, drug device combinations and the importance of real-world evidence in regulatory decision-making.

Click here to view the BIA/MHRA Conference report in full.

MHRA consultation on EU exit no-deal legislative proposals

The UK is exiting the EU on 29 March 2019. The terms and conditions are still currently being negotiated. The MHRA is preparing for all potential outcomes including the worst case scenario. The MHRA opened a consultation on how its legislation and regulatory processes would have to be modified in the event of the UK not securing a deal with the EU after the UK’s exit, with no implementation period.. The consultation covers no-deal proposals on medicines, clinical trials and medical devices. The MHRA said that the below principles having been applied:

  • pragmatic and proportionate approach in establishing UK regulatory requirements.
  • the UK regulator’s ability to take regulatory action to protect public safety.
  • minimum disruption and burden on companies as the UK exits the EU

The MHRA is seeking stakeholders views on theirs proposals. The consultation will close on first of November 2018.

Click here to access to the consultation


European Commission (EC)

EC informs stakeholder about the impact of Brexit on clinical trials

This month, the EC published a note to stakeholders informing them about the implications of Brexit for clinical trials under a no-deal scenario. In the event of a no-deal Brexit scenario, the UK will become a 'third country' in relation to the EU This has the potential to impact a range of areas which are particularly pertinent to multi-centre clinical trials including:Supply of Investigational Medicinal Products (IMP): IMP imports from the UK to the EU would be subject to the holding of an authorisation which includes the holder to have permanently and continuously at their disposal the services of at least one qualified person located in the EU. This would still be required if only part of the manufacturing is performed in the UK (e.g. packaging or repacking, for example).

  • Establishment requirements for the sponsor or the legal representative: sponsor established in the UK and conducting a clinical trial in EU must ensure that a sponsor or a legal representative is established in the EU.
  • Submission of clinical trial information:
    • protocol-related information: UK-specific trial information will no longer have to be submitted to EudraCT, except when the trial is part of an agreed Pediatric Investigation Plan and the UK is the only country in which the protocol has been submitted.
    • result-related information: results of clinical trials conducted in the UK and completed before the withdrawal date must be submitted to EudraCT if the reporting of these results is due before the withdrawal date. Results of clinical trials conducted only in the UK and results of multi-country trials where the UK was the only EU/EEA Member state where the clinical trial was conducted have to be submitted to EudraCT, also after the withdrawal date, if this is required for non-EU/EEA studies.

Click here to view the note to stakeholders.

Please note the UK MHRA has also published its own technical guidance related to Brexit and is currently consulting on legislative proposals in the event of a ‘no-deal’ EU exit (see below).


Food and Drug Administration (FDA)

CBER clarifies the purpose/scope of the INTERACT meetings

In June, Food and Drug Administration's (FDA) Center for Biologics Evaluation and Research (CBER) launched a new program for early meetings with biologics developers. The new program, called INTERACT (INitial Targeted Engagement for Regulatory Advice on CBER ProducTs), replaces the existing pre-, pre-investigational new drug (IND) meeting program for all products regulated by CBER.

The format of these meetings is broadly comparable to those already available with the EMA’s Innovation Task Force (ITF) and MHRA’s Innovation Office (IO).

This month, the FDA further clarified the purpose/scope of the INTERACT meeting which aims to:

  1. assist sponsors conducting early product characterisation and preclinical proof-of-concept studies;
  2. initiate discussion for new delivery devices;
  3. inform sponsors about overall early-phase clinical trial design elements; and
  4. identify critical issues or deficiencies for sponsors to address in the development of innovative products.

The FDA also specifies the overall submission process and describes the high-level content of the application. The FDA aims to hold these meetings within 90 calendars days of request

Click here to view FDA press release.

FDA releases draft guidelines on adaptive clinical trial designs and master protocols for cancer trials

Adaptive designs for clinical trials of drugs and biologics

This guidance will replace the 2010 draft guidance for industry Adaptive Design Clinical Trials for Drugs and Biologics. The FDA defines adaptive design as “a clinical trial design that allows for prospectively planned modifications to one or more aspects of the design based on accumulating data from subjects in the trial”. The guidance describes important principles for designing, conducting, and reporting the results from an adaptive clinical trial. These concepts are particularly useful for early-phase or exploratory clinical trials as well as trials conducted to satisfy post-marketing commitments or requirements. The draft guideline also discusses the limitations of this approach as well as adaptive designs based on comparative data vs. non-comparative data.

Click here to access to the document.

Master protocols: efficient clinical trial design strategies to expedite development of oncology drugs and biologics

This guidance provides recommendations to sponsors of drugs or biologics for the treatment of cancer regarding the design and conduct of clinical trials intended to simultaneously evaluate more than one investigational drug and/or more than one cancer type within the same overall trial structure (master protocols) in adult and pediatric cancers. Also referred to as “basket” trials, these approaches intend to expedite late-stage drug development.

The draft guidance describes aspects of master protocol designs and trial conduct and related considerations, such as biomarker codevelopment and statistical analysis considerations. It also provides advice on the information that sponsors should submit to FDA and on how sponsors can interact with FDA to facilitate efficient review.

Click here to access to the document.

New draft guidance on labeling of biological products

In July, the FDA released a draft guideline on “Indications and usage section of labeling for human prescription drug and biological products”.

The document covers circumstances in which a clinical indication can be broadened or limited from what was initially approved based on clinical trial data. This 20-page document has been released in order to ensure indications and usage section within a product label is ‘clear, concise, useful, and informative and, to the extent possible, consistent within and across drug and therapeutic classes’.

It should be followed by applicants who are developing indications and usage section for a new drug and when revising this section for a currently approved drug, including when seeking approval of a new indication.

Click here to view the guideline in full

Public consultations



Consultation period


MHRA consultation on EU exit no-deal legislative proposals

04 Oct 2018 to 01 Nov 2019

Draft legislation




Consultation period


Good Clinical Practice for Advanced Therapy Medicinal Products

01 Aug 2018 to 31 Oct 2018

Draft guidance




Consultation period


Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management

16 Nov 2017 to 18 Dec 2018

Draft guidance