Regulatory news - May 2018

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 publishes two year report on PRIME scheme

PRIority MEdicines (PRIME) is a scheme launched by the European Medicines Agency (EMA) two years ago to enhance support for the development of promising medicines that target an unmet medical need. The scheme aims to offer early and proactive regulatory support to developers of promising medicines to optimise development plans with a view to accelerating the route to market.

The report details key figures on applications received and assessed since its launch which includes:

  • 177 requests for eligibility to PRIME since launch
    • More than half of the requests from SMEs
    • 3 from academic groups
  • 36 medicines accepted, the majority in oncology and hematology area
    • 15 Advanced Therapy Medicinal Products (ATMPs)
    • 16 for pediatric patient populations
    • 30 targeting rare diseases
  • 3 marketing authorisations currently under review – these are Kymriah (Novartis), Yescarta (Kite Pharma/Gilead Sciences) and Luxturna (Spark/Novartis)

EMA continues to receive a high number of PRIME requests for ATMPs which represent currently a large proportion (40%) of eligible products, reflecting the potential for this type of therapy to address unmet medical needs.

The report also outlines how the elgibility criteria have been applied and what type of support applicants have received so far.

  • The vast majority of the requests received are at proof of concept stage supported by (clinical) exploratory data. EMA highlights in the report that applicants from the academic sector and SMEs can apply earlier on the basis of compelling non-clinical data and clinical tolerability data but only eight of these have been granted, with only 1 being an ATMP (according to the list of products granted eligibility). According to the EMA, the main grounds for denial have been:
    • Issues with robustness of presented data,
    • Inconclusive or insufficient effect of the product,
    • Unmet need not acceptable or not sufficiently justified.
  • Based on largely positive feedback from the applicants, kick-off meetings appear to be a key benefit of the PRIME scheme. This is a unique type multidisciplinary meeting to agree on next steps to address any identified issues or to identify potential additional issues. The other key element is the availability and timing of scientific advice including multiple committees and other stakeholders i.e.: Health Technology Assessment -HTA or patients.

The EMA has integrated this experience in new document published this month:

Click here to view the report.

EMA publishes its 2017 Annual Report

EMA has published this month their annual report. The document provides an overview of the EMA work, key figures relating to regulatory procedure and highlights its last year’s major achievements. In 2017, EMA recommended two ATMPs for marketing authorisation:

  • Spherox to treat adult patients who have symptomatic cartilage defects in the knee joint,
  • Alofisel for the treatment of complex perianal fistulas in patients with Crohn’s disease.

ATMPs including CAR-T cells are discussed throughout as promising development and challenge. EMA is currently assessing the first two CAR T-cell products: Yescarta® and Kymriah® for European marketing authorisation The EMA has seen increasing numbers of ATMPs coming for scientific advice especially via PRIME suggesting that the number therapies approaching the market is likely to increase over the next few years.

Click here to access to the report in full.

EMA explores the use of existing patient registries to support safety and efficacy assessment of CAR T-cell therapies

Chimeric Antigen Receptor T-cell (CAR T-cell) therapies pose particular challenges for regulators and healthcare providers. Long-term “real life” is also essential to asses the benefit-risk profile of this products as part of their integration into our healthcare systems. In that context, EMA hosted a workshop in February to explore the opportunities and challenges of using existing patient registries to support CAR T-cell therapy benefit-risk evaluations and post-authorisation follow-up.

The participants with clinical, regulatory, or development experience with CAR T-cell products included representatives from two large registry holders; the European Society for Blood and Marrow Transplantation (EBMT) and the United States-based Centre for International Blood and Marrow Transplant Research (CIBMTR).

The observations/recommendations made during the workshop are compiled in a report published this month.

Key priorities from this workshop include:

  • to collect a set of core commonly-defined data elements – Appendix 1 provides the proposed data to be collected for efficacy and safety, its priority, the current capture status in EBMT and CIBMTR.
  • to harmonise data element definitions across registries,
  • to establish measures that ensure data are collected systematically with appropriate verification and quality assurance,
  • to ensure arrangements are in place to permit data sharing, and
  • to improve communications between registry holders, regulators and marketing authorisation holders and applicants.

Click here to view the report

European Directorate for the Quality of Medicines (EDQM)

EDQM publishes a guide on How to read a Certificate of suitability to the Monographs of the European Pharmacopoeia (CEP)

This document has been created with the intention of clarifying the information to be concluded from a Certificate of suitability to the Monographs of the European Pharmacopoeia (CEP) for industry and the competent authorities. It provides definition and content of the different CEPs. For instance, a Transmissible Spongiform Encephalopathy (TSE) CEP certifies that the substance complies with monograph 1483 of the Ph. Eur. “Products with risk of transmitting agents of animal spongiform encephalopathies”, and reminds that this type of CEP “does not certify that the quality of the substance is suitably controlled by a specific Ph. Eur. Monograph”.

Click here to view the guide


Food and Drug Administration (FDA)

FDA seeks permanent injunctions against two stem cell clinics

The FDA filed two complaints in federal court for permanent injunctions against US Stem Cell Clinic, the California Stem Cell Treatment and the Center California Stem Cell Treatment Center. The objective is to prevent patient administration of unproven and potentially dangerous stem cell products.

  • US Stem Cell Clinic was processing adipose tissue into stromal vascular fraction and administering the product both intravenously or directly into the spinal cord of patients to treat a variety of serious diseases or conditions
  • California Stem Cell Treatment Center was administering to cancer patients a stem product made of a combination of excess amounts of Vaccinia Virus Vaccine and stromal vascular fraction.

The good manufacturing practices (GMP) inspections revealed significant deviations from current GMP like failure to establish and follow appropriate written procedures designed to prevent microbiological contamination of products.

Despite warning letter, the clinics failed to come into compliance with the law, so FDA took action to protect patients.

On his statement Commissioner Scott Gottlieb emphasises that while FDA “supports sound, scientific research and regulation of cell-based regenerative medicine”, it will “continue to take enforcement actions against clinics that abuse the trust of patients and endanger their health with inadequate manufacturing conditions or by purporting to have treatments that are being manufactured and used in ways that make them drugs under the existing law but have not been proven safe or effective for any use.”

Click here to access to FDA press release.

FDA to release clinical development guideline on gene therapy

In the recent Annual Board Meeting of the Alliance for Regenerative Medicine (ARM) the FDA provided some updates to the US framework for regenerative medicines with a view to fostering greater innovative development in this field. This included:

  • Progression on the draft guidance on how FDA intends to apply the Regenerative Medicine Advanced Therapy (RMAT) designation.
  • Intent to release guidance documents articulating the framework for manufacturing and clinical development of gene therapy products. This new guidance will be focused on product-related issues, as well as recommendations for clinical development in certain indications including hemophilia.

Click here for more information.

Kymriah® receives second FDA approval to treat r/r patients with large B-cell lymphoma

Earlier this month, the FDA has approved an extension of Kymriah’s® intial approval for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy. This includes diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma and DLBCL arising from follicular lymphoma.

This approval is based on the pivotal phase II JULIET study. Kymriah® showed an overall response rate (ORR) of 50%, with 32% of patients achieving a complete response (CR) and 18% achieving a partial response (PR) in 68 patients evaluated for efficacy. The median duration of response was not reached at the time of cut-off indicating sustainability of response.

This approval puts Novartis’ Kymriah® in direct competition with Kite/Gilead’s Yescarta®, approved in the same indication by the FDA.

Click here to view the press release from Novartis.

Public consultations




Consultation period


Study supporting the Evaluation of the European Medicines Agency Fee System

02 May to 02 Aug 2018

Draft questionnaire

Targeted stakeholder consultation on duplicate marketing authorisations for biological medicinal products

18 May to 10 Sept 2018

Draft stakeholder consultation



Consultation period


Postmarketing Safety Reporting for Combination Products

21 Mar to 19 Jun 2018

Draft guidance



Consultation period


Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management

16 Nov 2017 to 18 Dec 2018

Draft guidance