Regulatory news - August 2019

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


Medicines and Healthcare products Regulatory Agency (MHRA)

Further Guidance from the MHRA for a no-deal Brexit

The MHRA has published further guidance for industry and stakeholders in the event of a no-deal Brexit.

Further guidance note on the regulation of medicines, medical devices, and clinical trials if there’s no Brexit deal

If there is a no-deal Brexit, the UK will no longer participate in the European medicines regulatory network (EMRN) and the MHRA would take on the functions currently undertaken by the EU for human medicines on the UK market. All current Centrally Authorised Products (CAPs) will automatically become UK Marketing Authorisations (MAs) on exit day. Marketing Authorisation Holders (MAHs) will have 1 year from exit day to provide the MHRA with baseline data for CAPs that are converted into UK MAs. However, holders will have a short period of time after exit day to opt-out of having a UK MA if they so choose. The MHRA will also have oversight of all pharmacovigilance activities.

The MHRA will offer new assessment procedures for applications with products containing new active substances and biosimilars alongside the existing 210-day national licensing route.

The UK will have a system for rare disease medicinal products with orphan status determined at the point of MA. The orphan criteria will still be based on the current EU criteria, but UK-specific data will be incorporated.

The MHRA will not charge a fee for scientific advice to any small and medium-sized enterprises (SMEs) established in the UK. This is to provide support to SMEs and help retain research and development in the UK.

The MHRA will also have a system for Paediatric Investigation Plans (PIPs), with the same rewards as the EU system for PIP compliance.

The UK will continue to recognise QP certification from EU/EEA countries after Brexit. However, to ensure public safety, the MHRA will limit this to purchase of medicines that have been QP certified in the EU/EEA.

With a no-deal Brexit, the UK’s current participation in the EU regulatory network for clinical trials would end, and the MHRA would take on the regulation of clinical trials for the UK. The UK will continue to recognise existing approvals - both for regulatory and ethics approvals.

To read the full article see here.

List of approved countries for authorised human medicines if there is a no-deal Brexit

In the event that the UK leaves the EU without a deal, the Human Medicines Regulations 2012 will refer to lists of countries approved for the following activities:

  • import of medicines under a wholesale dealer’s license;
  • batch testing of medicines;
  • manufacturing of active substances with regulatory standards equivalent to the UK.

The guidance released by the MHRA provides the lists of countries and a summary of the circumstances under which the lists can be used.

For more information see here.

Guidance on qualified person responsible for pharmacovigilance (QPPV) including pharmacovigilance system master files (PSMF) in a no-deal Brexit

In a no-deal scenario, marketing authorisation holders (MAH) are to operate a pharmacovigilance system for UK authorised products, have an appropriately qualified person responsible for pharmacovigilance (QPPV) that resides and operates in the UK and maintain and make available upon request a PSMF that describes the pharmacovigilance system for UK authorised products. There will be a temporary exemption in place which allows you until 21 months after exit day to appoint a UK QPPV that resides and operates in the UK.

For more information see here.

Guidance on substantial amendments to a clinical trial if the UK leaves the EU with no deal

This guidance applies to substantial amendments to a clinical trial including changes to the trial sponsor/legal representative, investigational medicinal product (IMP) certification and importation and amendments to the Research Ethics Committee (REC).

For changes to the trial sponsor/legal representative, an amendment would need to be submitted to both the MHRA and REC. In the event of a no-deal Brexit, where the sponsor is from the rest of the world and has a legal representative in the UK and sites in the EU/EEA, the sponsor will need to assign an EU/EEA legal representative for the EU/EEA sites.

A substantial amendment will be required for submission to the MHRA for a change to any IMP manufacturing, importation or certification site relevant for supply of IMP to an ongoing UK trial.

For more information see here. The Health Research Authority (HRA) has also produced guidance on handling amendments in a no‑deal Brexit, clarifying when amendments are required to be submitted for REC review.

Guidance on handling of Decentralised and Mutual Recognition Procedures in a no‑deal Brexit

The MHRA has provided guidance describing the approach they intend to take for products approved or pending in decentralised procedure (DCP) or mutual recognition procedures (MRP) for a no-deal Brexit.

All medicinal products approved in the UK via DCP or MRP before the UK leaves the EU have been issued with a national (UK) MA. These MAs will be unaffected and remain valid in the UK. Any subsequent variation to the MA will need to be submitted as a national variation using current procedures.

All ongoing DCP/MRP procedures that are positively finalised on or before the day the UK leaves the EU but are in the 30-day national phase of the procedure, will continue to be processed and issued with a national (UK) MA.

For more guidance about pending DCP or MRP procedures see them here.

Licensing of biological products: biosimilars and ATMPs in a no-deal Brexit

The MHRA has offered guidance for biological products in a no-deal Brexit.

The guidance covers new applications and assessment procedures for biosimilars and how ATMPs will be regulated and assessed post-Brexit.

For more information see here.

Guidance note on new assessment routes in a no-deal Brexit

The MHRA will be introducing new routes of assessment for evaluation of marketing authorisation applications which include targeted assessment, accelerated assessment and a rolling review.

Targeted assessment (TA) process

The TA “intended to support the timely availability of new medicines for patients in the UK”. Timelines for approval will be within 67 days of submission. A positive scientific opinion from the Committee for Medicinal products for Human Use (CHMP) is needed to be eligible for TA.

Accelerated Assessment pathway

The ‘Accelerated Assessment’ process is “aimed at enhancing the availability of novel medicines for patients in the UK.” Timelines for approval will be within 150 days of submission. Accelerated Assessment applies to all products containing new active substances, including biologicals for whom the applicants wish to obtain a marketing authorisation in the UK.

Rolling Review route

The Rolling Review is a new route for MA applications intended to enhance development of novel medicines by offering on-going regulatory input and feedback.

For further information see the full guidance document here.

Dr June Raine to become interim Chief Executive Officer of the MHRA

Dr June Raine will become interim Chief Executive of the MHRA from 20 September 2019 replacing Dr Ian Hudson who steps down after 18 years with the agency.

To read the full article see here.

Human Tissue Authority (HTA)

EU Exit Guidance Update

The HTA has published guidance for the Human Application and Organ Donation and Transplantation sector in relation to import and export of tissues and cells to and from the EU/EEA following Brexit.

In the event of a no-deal Brexit, the UK will become a third country for the purposes of the EU Tissues and Cells Directive and the EU Organ Donation Directives. The UK will also consider EU/EEA Member States to be third countries. Consequently, tissues and cells from EU/EEA Member States would need to be covered by the appropriate HTA import license. An export license will be required to send tissues and cells to any EU/EEA Member State.

There will be a six-month transitional period to allow establishments time to comply with any new UK requirements.

Two statutory instruments were published in November 2018:

Please see here for the full article.


Food and Drug Administration (FDA)

FDA Rejects Sarepta Therapeutics' Therapy for Duchenne Muscular Dystrophy (DMD)

The FDA have rejected Sarepta Therapeutics' New Drug Application for Vyondys 53. The agency refused the application due to the risk of infection linked to intravenous infusion ports and kidney toxicity seen in pre-clinical studies.

Vyondys 53 was designed to treat approximately 8% of Duchenne patients with a specific genetic mutation.

Sarepta will request a meeting with the FDA to determine next steps.

See here for the full press release.


Pfizer Invests $500M to Advance Gene Therapy Manufacturing Facility

Pfizer is investing $500 million into a manufacturing plant in North Carolina and will hire another 300 workers. The larger facility will allow Pfizer to support their continuing investment in gene therapy research and development and produce and supply both clinical- and commercial-scale quantities of gene therapy medicines to patients around the world.

See here for the full press release.


International Conference on Harmonisation (ICH)

ICH to Hold Global Meeting on E8(R1) Guideline on General Considerations for Clinical Trials

The ICH will hold a global meeting on E8(R1) in October 2019 to provide information and get input from non-ICH Members and stakeholders on the draft revised E8(R1) Guideline “General Considerations for Clinical Trials.”

The draft guideline was released for public consultation in May 2019.

See here for the full press release.

Alliance for Regenerative Medicine’s (ARM)

ARM Issue Principles for Human Genome Editing

ARM released a statement of principles setting out their bioethical framework for the use of gene editing in therapeutic applications.

ARM’s five key principles for the ethical use of gene editing and genetic modification include:

  1. The endorsement of investigation of therapeutic applications of somatic cell gene editing;
  2. Supporting the use of gene editing standards to facilitate the development of safe and efficacious gene-editing therapies;
  3. Supporting continued evolution of national and regional regulatory frameworks governing the development of somatic cell gene editing techniques;
  4. Identifying that germline gene editing is currently inappropriate in human clinical settings until safety, ethical, legal and societal issues are resolved;
  5. Common commitment to focusing on somatic cell approaches to therapeutic treatments and cures for disease.

See here for the full press release and here for the final statement of principles.

World Health Organisation (WHO)

WHO Launches Global Registry on Human Genome Editing

A new global registry to track research on human genome editing has been approved by a WHO expert advisory committee.

Dr Tedros Adhanom Ghebreyesus, WHO’s Director-General, said “new genome editing technologies hold great promise and hope for those who suffer from diseases we once thought untreatable. But some uses of these technologies also pose unique and unprecedented challenges – ethical, social, regulatory and technical”.

To ensure the registry is fit for purpose and transparent, the advisory committee will engage with a range of stakeholders on how it will operate through online consultations and in-person engagement.

For more information see here.

Public Consultations






ICH guideline E8 (R1) on general considerations for clinical studies

10 May to 30 Sept 2019

Public consultation



Consultation period


Population Pharmacokinetics

11 July to 11 Sept 2019

Public consultation

Providing Regulatory Submissions in Electronic Format – Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications

16 July to 16 Sept 2019

Public consultation

Rare Pediatric Disease Priority Review Vouchers

30 July to 28 Sept 2019

Public consultation