Regulatory News - July 2021

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)

Combined Review Process for Clinical Trials

The MHRA have announced plans to streamline the review of clinical trials for medicinal products. In partnership with the Health Research Authority (HRA), the agency have developed the combined review service (formerly known as Combined Ways of Working (CWoW)), which offers a single application and co-ordinated review leading to a single UK decision for clinical trials of investigational medicinal products (CTIMPs). This work is part of the transformation of the Integrated Research Application System (IRAS) being led by the HRA in collaboration with the MHRA, the devolved administrations, the National Institute for Health Research (NIHR) and other research partners.

From January 2022 all new CTIMPs in the UK will be subject to a combined review from the MHRA, Research Ethics Services and HRA. However, the service is now in operation, and applicants are encouraged to start using the service prior to January 2022 to ensure internal systems and processes are aligned in time for full implementation.

For more information, see here. The combined review platform is available here.


European Medicines Agency (EMA)

How Sponsors can Prepare for the Clinical Trials Information System

The Clinical Trials Information System (CTIS) has been created as part of the EU Clinical Trials Regulation (Regulation (EU) No 536/2014) and will act as the single-entry point for clinical trials authorisation and supervision in the EEA. The EMA hosted a webinar on the 29th July 2021 to further inform on how sponsors can prepare for the implementation of the CTIS. Topics presented include:

  • how sponsor organisations can prepare ,
  • how Member States aim to support sponsor preparedness and adoption,
  • the role of the Clinical Trial Regulation,
  • how sponsors can best make use of EMA’s CTIS training materials.

A recording of the webinar will be available after the event.

The webinar recording will be uploaded here. See here for further information on the EU Clinical Trial Regulation and CTIS.

EMAGuideline on Quality Documentation for Medicinal Products when used with a Medical Device

The EMA have released a guidance document describing the information that should be presented in the quality part of a marketing authorisation dossier for a medicinal product when it is used with a medical device.

There is a focus on product-specific quality aspects of a medical device (integral, co-packaged or separately obtained and referenced in the product information) that may have an impact on the quality, safety and efficacy of a medicinal product.

This guideline should be read in conjunction with the Q&A on the implementation of the Medical Device Regulation.

The guidance document is available here. The Q&A on the implementation of the Medical Device Regulation can be accessed here.

EMA Review Zynteglo Viral Vector Link to Blood Cancer

Zynteglo, a gene therapy for treatment of the blood disorder beta thalassaemia which uses a viral vector to deliver working copies of the beta-globin gene into patients’ blood cells, has been under review amidst concerns the viral vector used in the gene therapy may result in insertional oncogenesis.

The review assessed two cases of acute myeloid leukaemia (AML) in patients participating in a clinical trial for sickle cell disease, who had been treated with an investigational medicine (bb1111), which uses the same viral vector as Zynteglo. No cases of AML have been reported for Zynteglo, however as both medicines use the same viral vector there was a concern the vector may be implicated in the development of the cancer.

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) and Committee for Advanced Therapies (CAT) completed the review, concluding that the viral vector was unlikely to be the cause. The viral vector was not present in the cancer cells in one patient, and its presence was detected in the second patient but at a site (VAMP4) that does not appear to be involved in cancer development.

The Committee for Medicinal Products for Human Use (CHMP) endorsed the review findings and has agreed updated monitoring recommendations for patients. Going forward, patients should be checked at least once a year over 15 years for signs of blood cancers. It was previously recommended to check patients once a year.

For further information and all CHMP recommendations, see here.

European Commission (EC)

Gene Therapy Skysona Approved for Treatment of Early CALD

On 21 July the EC approved bluebird bio’s gene therapy Skysona, a one-time gene therapy for the treatment of early cerebral adrenoleukodystrophy (CALD) in patients less than 18 years of age, who do not have a matched sibling blood stem cell donor. CALD is a rare neurodegenerative disease caused by mutations in the ABCD1 gene primarily affecting males. This life-threatening disorder occurs in childhood and can rapidly lead to progressive and irreversible loss of neurologic function.

SKYSONA uses ex vivo transduction with the lentiviral vector Lenti-D to add functional copies of the ABCD1 gene into a patient’s own hematopoietic stem cells (HSC). Previously, the only therapeutic option available to CALD patients was transplantation of donor stem cells.

2 years after treatment, Skysona was shown to stabilise disease by preventing further inflammation and destruction of the myelin of nerve cells in patients.

See here for bluebird bio press release and here for EMA overview.


Food and Drug Administration (FDA)

FDA Q&A on Enforcement Policy for Human Cells, Tissues, or Cellular or Tissue-Based Products

The FDA guidance Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use was released in November 2017 and updated in July 2020. Aligned with this guidance, a 3-year period of compliance and enforcement discretion was in place to allow manufacturers of human cellular and tissue-based products (HCT/Ps) to bring their processes in line with the new regulations, ensuring compliance with Investigational New Drug (IND) and pre-marketing approval requirements. All establishments that manufacture HCT/Ps regulated as drugs or biological products must have an approved biologics licence application (BLA) in place to lawfully market these products, or while in development stages an IND must be in effect for distribution for clinical use.

This period of discretion came to an end on 31st May 2021, meaning that the agency no longer intends to exercise enforcement discretion for IND and pre-market approval requirements. The FDA’s Center for Biologics Evaluation and Research (CBER) have released a Q&A document for industry to address challenges which may arise now that this discretion policy has come to an end.

To read the Q&A document, see here.


National Pharmaceutical Regulatory Agency (NPRA)

NPRA Publish Cell and Gene Therapy Manufacturing Guidance

Malaysia’s NPRA has released a Guidance Note for Cell and Gene Therapy Products (CGTPs) Manufacturing Facility in Malaysia. The guidance aims to inform organisations and establishments in setting up manufacturing facilities for CGTPs and describes the regulatory process requirements, including details on good manufacturing process (GMP) inspections involved.

The guidance sets out the legal requirements and practical steps for organisations to follow, with direction for preparation of a Pharmaceutical Quality System and frequently asked questions.

The guidance document is available here.

Pharmaceutical Inspection Co-operation Scheme (PIC/S)

PIC/S Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments

The PIC/S has announced the finalisation of its new guidance on good practices for data management and integrity for pharmaceutical manufacturers and distributors. The guidance is applicable to both on-site and remote inspections of sites performing GMP and GDP activities, aiming to assist the Inspectorate in planning risk-based inspections in relation to data management.

See here for the final guidance document.

Public Consultations







ICH S12 guideline on nonclinical biodistribution considerations for gene therapies

24 Jun 2021


24 Oct 2021

Public Consultation