Regulatory news - March 2019

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


European Medicines Agency (EMA)

EMA Now Operating from Amsterdam

The EMA left its London premises on the 1 March and moved into it’s temporary premises, the Spark building, Amsterdam Sloterdijk. The EMA will operate out of the Spark building until the permanent premises in Amsterdam Zuidas becomes available.

Read the full article here.

EMA Qualifies CAR T-Cell Therapy Registry

The EMA has qualified the European Society for Blood and Marrow Transplantation’s (EBMT) registry as a suitable platform for the collection of data for post-authorisation safety surveillance and efficacy studies. This allows the EBMT to perform pharmacoepidemiological studies for regulatory purposes concerning Chimeric Antigen Receptor (CAR) T-cell therapies used in the treatment of haematological malignancies. This was in response to the EMA’s Patient Registry Iniative.

The EBMT is now suitable for the collection of data for post-authorisation safety surveillance and efficacy studies.

Jürgen Kuball, EBMT treasurer and liaison with the EMA, says: “This recognition will lead to an improved communication across the various stakeholders, including registry owners, regulators and marketing authorisation holders, giving confidence to users on the data collected and ultimately bring safe and effective therapies to our patients”.

The registry was used in the evaluation of Zalmoxis which was granted conditional authorisation by EMA in 2016. “The EBMT registry allowed for a matched pair analysis comparing the outcome of patients who received Zalmoxis versus those being treated as standard of care”.

The press release is available here, to view the qualification opinion report, see here.

Zynteglo Receives Positive Opinion from the EMA

The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion and recommended granting a marketing authorisation for the medicinal product Zynteglo. Bluebird Bio’s Zynteglo is a gene therapy to treat transfusion-dependent β-thalassemia (TDT). The gene therapy “adds functional copies of a modified β-globin gene into the patients’ haematopoietic stem cells through transduction of autologous CD34+ cells with BB305 lentivirus vector, thereby addressing the underlying genetic cause of the disease”.

Zynteglo was designated as an orphan medicinal product in 2013 and underwent review through the EMA’s accelerated assessment programme.

See here for the opinion from the EMA.

United Kingdom

Medicines and Healthcare products Regulatory Agency (MHRA)

Webinars Related to Making Submissions to the MHRA if the UK Leaves the EU with No Deal

The MHRA has published a series of webinars which cover how stakeholders can make informed IT plans and preparations in the event of leaving the EU with no deal.

Preparations have been made so that if the UK leaves with no deal, applicants can continue to submit regulatory and notification information to the UK.

If the UK leaves with no deal, the UK will no longer be part of the EU medicines and medical devices regulatory networks and submissions related to human medicines would need to be submitted directly to the MHRA. A contingency programme has been put in place should the UK lose access to the current EU IT systems.

The MHRA are continuously updating their guidance for a no deal scenario. The National Institute for Biological Standards and Control (NIBSC) has provided guidance for manufacturers of biological medicines, information for customers of biological reference materials and information for NIBSC collaborators. Guidance for importing and exporting, pharmacovigilance systems, marketing authourisations, licensing of biological products such as ATMPs, registration of clinical trials for investigational medicinal products, UK paediatric investigation plans (PIPs) and guidance on national scientific advice has also recently been added.

See here for the webinars and further guidance. For the latest updates on guidance for a no deal scenario see here.

MHRA GXP Data Integrity Guidance: Part 1 – A GCP Perspective

The MHRA guidance for GXP Data Integrity (DI) was published in March 2018 and since then, has been well received by the industry and stakeholders. To futher engage with stakeholders, the MHRA is welcoming feedback on guidance issued by issuing a series of GXP blog posts to assist further on the reflections received since the release of the guidance. The posts start with the Good Clinical Practice (GCP) perspective.

Audit Trail Review

The guidance describes the need for a documented audit trail review to identify the trial risks. Sponsors questioned whether there would then be a need to develop Standard Operating Procedures (SOPs) to cover this process. The response from the MHRA was that the need for a review of an audit trail should be determined by a risk assessment based on the requirements of the trial and therefore, to have a generic SOP would not add any benefit to the process and is not mandated by the guidance or expected by GCP inspectors.

Recording of Patient Data

The MHRA made some clarification in regard to having a second person verifying the recording of patient data from a recording instrument. In clinical trials, the same person performing the task can also complete the clinical trial record.

Amount and Resolution of Data to be Collected

The MHRA have been asked what it means to collect data that ‘allows the full reconstruction of activities, the amount and the resolution (degree of detail) of data to be collected’, as per section 6.7 of the DI guidance. Organisations questioned whether they would need to develop an SOP for determining the amount and resolution of data to be collected.

The reponse from the MHRA was that “determining the amount and resolution of the data to be collected is an integral part of clinical trial quality/data management as defined by ICH E6(R2)”. This is usually documented as part of the organisations overall quality management planning, therefore it is up to the organisation to determine the best approach as per their quality system. There is no requirement to have a stand alone SOP.

For the full article see here and see here to view the guidance.


ANSM Introduces Fast-Track Authorisations of Clinical Trials

Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM) is introducing a fast track review process, aiming to speed up the processing and authorisation of clinical trial designs. For ATMPs there are two types of fast-track proposed:

FT1 – Access to innovation: Rapid access to advanced therapy products for patients (new substance or new combination) in clinical trials.

FT2 – Support for development: Accelerate the implementation of clinical trials for substances or combinations of substances already evaluated by the ANSM.

The ANSM target providing a final decision in a maximum of 110 days for FT1, and a maximum of 60 days for FT2 after receipt of a complete CTA for ATMPs.

For further information, see the Practical Information Guide for Applicants.


Food and Drug Administration (FDA)

CBER Finalises Guidance on Use of Standards in Regulatory Submissions

The FDA’s Center for Biologics Evaluation and Research (CBER) finalised guidance on the use of standards in product development and the use of such standards in CBER’s review process.

The guidance offers a series of questions and answers. It explains how the use of standards “can facilitate development by reducing the need to develop unique methods and/or reference materials for individual products” and for data standards “can help promote effective and efficient review of regulatory submissions”.

See here for the guidance document.

Scott Gottlieb Resigns as FDA Commissioner

Scott Gottlieb announced his resignation on 5 March.

Gottlieb advanced the regulatory framework for approving novel technologies, including advancing the reviews of cell and gene therapies. National Cancer Institute Director Ned Sharpless will become the interim leader of the FDA in early April once Scott Gottlieb's resignation becomes effective.

For the full article, see here.

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