Regulatory news - July 2019

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


European Commission (EC)

Batch Testing Must be Transferred from the UK to EU by 2020

The EC have released further information on batch testing of medicinal products in the context of withdrawal of the UK from the EU. The agency has published a notice reiterating the requirement for Marketing Authorisation (MA) holders to ensure that all batch testing facilities are fully transferred to the EU27 Member States and/or EEA countries by 2020 if the UK becomes a third country. Currently, unless the Withdrawal Agreement is endorsed and in place by 31 October 2019, or a further extension period is requested, the UK will become a third country as of 1 November 2019.

In such case, MA holders must ensure they are prepared to have all batch testing facilities transferred to the EU27/EEA and necessary regulatory submissions completed by 1 January 2020. In certain situations, competent authorities may allow continued batch testing in the UK for a limited period of time after the withdrawal date, covered by ‘the exemption’, under the following conditions:

  • A batch release site in the EU27/EEA is identified by the MA holder by the withdrawal date;
  • The batch release site is supervised by a qualified person established in the EU27/EEA by the withdrawal date;
  • The establishment designated by the third party conducting the quality control testing may be verified by a competent authority of the EU27/EEA, including on the spot checks;
  • All necessary steps have been taken to prepare the transfer of the quality control testing from the UK to the EU27/EEA.

This requirement will have significant impact on MA holders for ATMPs undergoing batch release testing in the UK, particularly for products with short shelf-lives or those for in vivo administration. MA holders are advised to ensure an agreed strategy is in place to reduce the risk of logistics and supply challenges.

To read the full notice, see here.

EU and US Reach a Milestone in the Mutual Recognition Agreement

The European Union (EU) and the United States (US) have now fully implemented the Mutual Recognition Agreement (MRA) for inspections of manufacturing sites for medicinal products in their respective territories. EU national authorities and the FDA have inspected many production sites of medicinal products in the EU, US and elsewhere in the world, auditing their supervisory systems to ensure they are in compliance with good manufacturing practice (GMP), and to confirm comparable procedures are in place to carry out GMP inspections. With the final positive assessment of Slovakia, this process has now been concluded for GMP inspectorates.

Now that the MRA is fully implemented, EU and US regulators can rely on each other’s inspections for human medicines production in their own territories, avoiding duplication of work.

For more information, see here.

European Medicines Agency (EMA)

EMA Call for Sponsors to Publish Clinical Trial Results in EudraCT

The EC, EMA and Heads of Medicines Agencies (HMA) co-signed a letter reminding all sponsors of clinical trials conducted in the EU of their obligation to prepare summaries of results of concluded trials publicly available in the EU Clinical Trials Database (EudraCT). It has been the responsibility of sponsors to ensure that protocol information and results of all clinical trials is submitted in EudraCT one year after the end of trial (or six months for a paediatric trial) since July 2014. This information is then made publicly available in the EU Clinical trials Register (EU CTR). A review of the number of clinical trials posted in EudraCT was conducted in April 2019, showing there is significant progress to be made to improve compliance on posting results.

As a result of this, the MHRA has also updated their guidance on ‘Clinical trials for medicines: manage your authorisation, report safety issues’ to include further information for end of trial procedures, reminding sponsors of their responsibility to publish summaries of results of concluded trials in EudraCT, in line with the EMA requirement.

For further information, see here. To read the joint letter by the EC, EMA and HMA, see here.

EMA and FDA Publish Report on Supporting Developers in Early Access Approaches

The EMA and FDA held a workshop, which was a joint collaboration between the EMA and its relevant working parties (Biologics Working Party [BWP], Quality Working Party [QWP] and Inspector’s Working Party [IWP]) and the US, on 26 November 2018. The aim being to discuss scientific and regulatory approaches to addressing quality and manufacturing challenges encountered during the development of medicines under early access programmes, such as the PRIority MEdicines scheme (PRIME) in the EU and Breakthrough Therapy designation in the US. The report summarises the discussions and conclusions from the workshop, including specific industry case studies covering biologics and ATMPs. Some key areas of discussion included:

  • Quality (CMC) challenges with accelerated development and early access programmes where data requirements must be in line with scientific guidelines according to the EU legislation (Annex I of Dir. 2001/83/EC).
  • Support for ATMP PRIME applications; where it is not possible to meet all the legislative requirements, the content of the application can be adapted under a risk‑based approach and relevant alternative sources of data (e.g. platform/pilot scale data) may be considered.
  • Out of specification (OOS) products, the importance of quality risk management and possible administration of cell/tissue based ATMPs that are OOS. The management of OOS ATMPs and supply of products where the risk from GMP limitations must be carefully balanced against the benefit to patients. This topic was highlighted by the agencies for further follow-up, particularly in the case of autologous treatments.
  • ATMP comparability challenges encountered during the manufacture of autologous products; due to the high-unmet medical need, and thus short development timelines of ATMPs, in conjunction with limited product and process understanding, process changes during development are inevitable, even in late stage development or post-approval. Thus, comparability exercises are required more frequently for ATMPs and are usually more complex compared to biopharmaceuticals. Where proposed process changes are concerned, a robust risk assessment is the basis for the decision of whether comparability studies are required as well as the design of the studies.

For further information, see here. The full report is available here.


Medicines and Healthcare products Regulatory Agency (MHRA)

Continuity in Uncertain Times: MHRA Brexit Provisions Webinar

Dr Christiane Niederlaender (Acting Unit Manager, Biologicals Unit) from the MHRA joined CGT Catapult to discuss the provisions the MHRA is putting in place to prepare for the UK’s departure from the EU.

The webinar ‘Continuity in uncertain times: MHRA Brexit provisions’ covered the following topics:

  • MHRA preparations for different outcomes of the UK Brexit negotiations;
  • The regulatory framework for the event of a no deal scenario;
  • Options for ‘in-flight’ applications;
  • New assessment time frames and opportunities;
  • Alignment with the EU.

The webinar recording is available to watch here, and the presentation slides can be found on the CGT Catapult website.


Food and Drug Administration (FDA)

CBER Plans Draft Guidance on ‘Sameness’ of Gene Therapies Under Orphan Drug Regulations

The FDA’s Center for Biologics Evaluation and Research (CBER) has added a new draft guidance on the list of guidance document it plans to publish this year: ‘Interpreting Sameness of Gene Therapy Products Under the Orphan Drug Regulations’. This guidance will be highly anticipated seen as around 70% of gene therapies are developed for rare diseases. In addition to this, CBER also plan to release the following guidance for this year, highlighting their focus on gene therapy topics:

  • Human gene therapies for hemophilia, retinal disorders and rare diseases;
  • Chemistry, manufacturing and control (CMC) information for human gene therapy IND applications;
  • Interpreting the sameness of gene therapy products under orphan drug regulations;
  • The testing of retroviral vector-based human gene therapy products for Replication Competent Retrovirus (RCR) during product manufacturing and patient follow-up;
  • Long term follow-up after human gene therapy product administration; and
  • Working with the FDA on complex and innovative clinical trial designs for drugs and biological products.

For more information, see here. The Guidance Agenda: Guidance Documents CBER is Planning to Publish During Calendar Year 2019 can be found here.

Public consultations



Consultation period


Guideline on the quality requirements for drug-device combinations[1]

03 Jun to 31 Aug 2019

Draft guidance

[1] Only applicable to ATMPs where a device is considered part of the container closure system. The guideline does not apply to combined ATMPs



Consultation period


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