Regulatory news - April 2019

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


European Commission (EC)

Commission Outlines How EU Data Protection Rules Affect Clinical Trial Sponsors

The EC has published a document detailing the interplay between clinical trial rules and the General Data Protection Regulation (GDPR). The document sets out the data protection requirements of the incoming Clinical Trials Regulation (CTR) and how they interact with GDPR.

The CTR places stronger requirements on sponsors to record, process, store and handle data in ways that enable accurate reporting and interpretation, without threatening the confidentiality of the records. However, the data are also subject to requirements of GDPR and the Commission thinks the onus is on sponsors to ensure data are processed in accordance with data protection rules.

How CTR and GDPR apply depends on whether data is being processed purely for research or if the activity has a health protection objective. The question and answer document created by the Commission sets out the regulations that apply in each situation and their implication for sponsors.

To read the full Q&A document, see here.

European Medicines Agency (EMA)

Two Additional Countries to Benefit from the EU-US Mutual Recognition Agreement for Inspections

The FDA has confirmed the capability of two additional EU Member States to carry out good manufacturing practice (GMP) inspections at a level equivalent to the US. Bulgaria and Cyprus were included into the mutual recognition agreement between the EU and US on the 29th April 2019. This means that these Member States inspection results can replace the FDA’s own inspections.

For further information, see here.

EMA Grants PRIME Designation for Dystrophic Epidermolysis Bullosa (DEB) Gene Therapy

The EMA have granted Krystal Biotech PRIME designation for KB103, a first-in-class topical gene therapy for the treatment of the rare genetic skin disease dystrophic epidermolysis bullosa (DEB).

KB103 is a gene therapy to treat DEB, which is caused by a mutation in the COL7A1 gene responsible for the formation of collagen type C7 protein that anchors fibrils that bind the inner and outer skin layers together resulting in fragile skin. KB103 is a replication defective, non-integrating viral vector HSV-1 that has been engineered to deliver functional human COL7A1 genes directly to a patient’s dividing and non-dividing skin cells.

The EMA awarded PRIME designation for KB103 based on the clinical data to date from an ongoing phase I/II study coupled with non-clinical data.

To read the full article, see here.

United Kingdom

Medicines and Healthcare products Regulatory Agency (MHRA)

MHRA Offers Additional No-Deal Brexit Guidance

The MHRA has released updated information for biopharma companies related to substantial amendments to a clinical trial, updated guidance on applying to release a vaccine or blood product and an updated webinar on making submissions via MHRA Submissions.

The guidance on clinical trials makes clear that in the event of a no-deal Brexit, the UK would require the sponsor or legal representative of a clinical trial to be in the UK or a country on an approved country list, which would initially include EU/European Economic Area (EEA) countries. The MHRA have added that if the trial sponsor is from the rest of the world and the legal representative is established in the UK and there are sites elsewhere in the EU/EEA, the sponsor will need to assign an EU/EEA legal representative for these sites. Sponsors will be required to submit a substantial amendment to the MHRA to add or replace any investigational medicinal product (IMP) manufacturing, importation or certification site relevant for the supply of IMP in an ongoing UK trial. “If the sponsor chooses to retain an existing UK IMP release site for the ongoing UK trial but includes an additional EU/EEA site for trials in the EU/EEA only, then no substantial amendment to the MHRA will be required,” MHRA says. For further information, the MHRA guidance is available here.

Regarding the guidance on releasing blood products or vaccines to the market, the MHRA has added a section with guidance for the Official Control Authority Batch Release (OCABR) Release and Marketing Information Form processes in the event the UK leaves the EU without a deal. See here for the MHRA guidance.

There is also new content added to the MHRA Submissions webinar.

To read the full article, see here (MHRA’s guidance here).

MHRA Offers No-Deal Guidance On Pharmaceutical Product Certificates

The Certificate of Pharmaceutical Product (CPP) is a certificate issued in the format recommended by the World Health Organisation, which establishes the status of the pharmaceutical product and of the applicant for this certificate in the exporting country. The MHRA has published additional guidance covering the process for applying for a CPP in case the UK leaves the EU without a deal. Clarification is included on the CPP request service the MHRA provide and the process for issuing a CPP for a grandfathered centrally authorised product (CAP). A grandfathered CAP is a CAP marketing authorisation (MA) which is automatically converted to a UK MA.

This guidance is part of a series of 41 MHRA guidances and publications on a possible no-deal scenario that have been in development since January.

For further information, see here (MHRA’s guidance is here).


Food and Drug Administration (FDA)

FDA Propose Removing Specific Methods for Mycoplasma Testing in the Regulation to Allow for Alternative Methods to be used

The FDA have proposed to remove specific methods to detect the presence of Mycoplasma in virus harvest pools and control fluid pools of live and inactivated virus vaccines produced from in vitro living cell cultures, as currently required by 21 CFR 610.30. The proposal is part of the FDA’s implementation of the Trump Administration’s “two out, one in” executive order to reduce regulatory burden and provide additional flexibility, and FDA noted the action is needed since “it has become increasingly clear that the test for Mycoplasma requirements is too restrictive… because they specify particular methodologies when alternatives may be available that provide the same or greater level of assurance of safety”.

However, removing this regulation would not remove the requirements for Mycoplasma testing in biologic licence applications (BLA). “A manufacturer of a live virus vaccine produced from in vitro living cell cultures and inactivated virus vaccines produced from such living cell cultures would continue to be required to follow the Mycoplasma test requirements specified in its BLA, unless the BLA were revised to modify or replace the test through a supplement,” the proposal says.

For more information, see here (the FDA article is here).

FDA to Step Up Stem Cell Enforcement and Look Into Pathway for Low-Risk Treatments

The FDA warns that the agency will step up its enforcement efforts against companies illegally marketing stem cell therapies.

The agency are looking into new ways to “delineate an efficient development path” for low-risk stem cell therapies being developed by firms that have filed investigational new drug applications.

For more information, see here (the full article is here).

When a REMS is Necessary: FDA Finalises Guidance

The FDA finalised guidance from 2016 detailing the factors that the agency uses to determine whether a risk evaluation and mitigation strategy (REMS) is necessary for a drug. REMS is a required risk management plan that can include one or more elements to ensure that the benefits of a drug outweigh its risks.

The use of REMS is decided upon on a case-by-case basis and the finalised guidance explains the requirement to consider the following six factors in deciding whether a REMS is required:

  • The seriousness of any known or potential adverse event that may be related to the drug and the background incidence of such events in the population likely to use the drug;
  • The expected benefit of the drug with respect to the disease or condition;
  • The seriousness of the disease or condition that is to be treated with the drug;
  • Whether the drug is a new molecular entity;
  • The expected or actual duration of treatment with the drug;
  • The estimated size of the population likely to use the drug.

All six factors are considered together to inform the FDA’s REMS decision making process and no single factor is determinative as to whether a REMS is necessary. The relative importance or weight of each factor is a case specific inquiry according to the guidance.

For further information, see here (the FDA guidance is here).


International Conference on Harmonisation (ICH)

ICH Updates: What’s Coming in 2019 and Beyond

The FDA and Health Canada held a joint regional consultation on ICH guidelines that have reached Step 3 of the ICH process to highlight what to expect from the ICH over the coming year.

The following guidelines were key topics of discussion:

This revision of the E8 guideline includes the adoption of quality-by-design framework for clinical studies and expansion of the scope to include a broader range of study designs and data sources. The aim is to ensure the guideline is pertinent to today’s world reflecting the variety of clinical trial designs and ability to use more real-world data sources. The guideline is expected to reach Step 2b in early May 2019 and be issued for public consultation.

A new guideline is proposed to provide harmonised guidance on when it would be appropriate to use a targeted approach for safety data collection in some late stage pre-marketing or post-marketing studies, and how this approach would be implemented. Selective safety data collection might be able to occur in some subsets of patients in a trial, or when a drug is already approved by one regulator. However it is emphasised that such a selective approach must be discussed early on with regulators. The guideline is currently at Step 3 with EU setting comments due by 29th September 2019.

S11 deals with the nonclinical safety testing in support of paediatric medicines and industry groups recently called for changes to be made to reduce the need for juvenile animal studies. The guidance is at Step 3 and public comments will be discussed at the ICH meeting in June 2019.

This guidance provides recommendations for the validation of bioanalytical assays for chemical and biological drug quantification and their application in the analysis of study samples for both non-clinical and clinical studies. The document will be discussed at the ICH meeting in November 2019 to bring it into Step 3.To read the full article, see here. The full agenda of the meeting is available here.

Public consultations




Consultation period


A Risk-Based Approach to Monitoring of Clinical Investigations Questions and Answers

15 Mar to 14 May 2019

Draft questions and answers



Consultation period


Optimisation of Safety Data Collection

15 Mar to 14 May 2019

Draft guidance