Regulatory news - June 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)

Yescarta® and Kymriah® are recommended for marketing authorisation in Europe

Kymriah® and Yescarta® are two Chimeric Antigen Receptors (CAR) T cells products recommended for Marketing Authorisation (MA) by the Committee for Advanced Therapies (CAT) and Committee for Medicinal Products for Human Use (CHMP). These two products, which were approved in US in 2017, are the first CAR-T cells products to receive a favorable opinion in Europe.

The two Advanced Therapy Medicinal Products (ATMP) are based on collecting and genetically modifying patients own cells to express an CAR that targets CD19 to treat patients with particular heamtological cancers.

  • Kymriah is indicated for the treatment of paediatric and young adult patients (up to 25 years of age) with B-cell acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse, and in adult patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) after two or more lines of systemic therapy.
  • Yescarta is indicated for the treatment of adult patients with relapsed or refractory DLBCL and primary mediastinal large B-cell lymphoma (PMBCL), after two or more lines of systemic therapy.

The two products are also the first medicines recommended for MA that have been supported through EMA’s PRIority MEdicines (PRIME) scheme, a voluntary scheme launched within in the EU in 2016 which aims to enhance and accelerate the development of medicines that target an unmet medical need.

Innovative treatments such as CAR-T cells have potential to change the outlook for patients with cancer” commented the chair of the CHMP.

The opinions adopted by the CHMP are an intermediary step on Kymriah® and Yescarta® path to patient access. The CHMP opinions will now be sent to the European Commission for the adoption of decisions on EU-wide MA. Once the MA has been granted, decisions about price and reimbursement will take place at the level of each Member State (MS), taking into account the potential role/use of these medicines in the context of the national health system of that country.

Click here for more information.

Click here to view Novartis press release (Kymriah®).

Click here to view Kite Pharma press release (Yescarta®).

EMA drafts qualification opinion on cell therapy module of EBMT Registry

Kymriah® and Yescarta® are innovative products that have great potentials, but they come with unique scientific and regulatory challenges. From a clinical perspective, these products can be associated with immediate severe adverse event like Cytokine Release Syndrome (CRS), which is a systemic response to the activation and proliferation of CAR-T cells causing high fever and flu-like symptoms, and neurologic toxicities which can be life-threatening and, in some cases, even fatal. Additionally, the long-term efficacy and safety of these treatment is still unknown.

For these reasons, it is crucial to establish a robust system of safety data collection for the post-authorisation phase. The methods should allow a tight monitoring of the benefit-risk profile of these medicines and allow a better risk management of the side effects. As part of that work, the EMA has released a draft qualification opinion on European Society for Blood & Marrow Transplantation (EBMT) registry for collection of post-authorisation safety and efficacy data.

The EBMT Registry holds data on patients given a Haematopoietic Stem Cell Transplantation (HSCT) procedure. EBMT has developed the Minimal Essential Data form for Cellular Therapy, including chimeric antigen receptor (CAR)-T cell therapy.

This draft qualification opinion is now open for public consultation until 21 August 2018. The report provides detailed information on cellular therapy module of the EBMT registry together with CHMP’s response to the questions posed by EBMT.

Click here to view the draft qualification opinion.

EMA launches a new submission portal for orphan designation application

As part of a longer-term program that aims to make the handling of product-related applications easier, the EMA has launched a new secure online portal for sponsors to submit applications for orphan designation.

The portal, named 'Iris', provides a single space where applicants can submit and manage the information and documents related to their applications for orphan designation. This is expected to reduce the time needed to prepare and submit the applications. Furthermore, during the review process, applicants can check the status of their applications and receive automatic notifications.

Guidance document have been updated according to the new submission process and applicants are strongly encouraged to start using the new portal from today athough the already existing submission process is still valid until 19 September 2018.

In future, the new IRIS system may be extended to include other procedures.

Click here for more information.

EMA/EC updates guidance and Q&A on Brexit preparedness

The EMA/EC continues to prepare pharmaceutical companies on Brexit by covering new topics on their guidance and Q&A documents on Brexit preparedness. The updated versions include now information on how the UK’s withdrawal will affect

  • the status of inspection outcomes by the UK national competent authority,
  • CE certification of medical devices by UK notified bodies,
  • scientific opinions of the CHMP for ancillary medicinal substances in medical devices requested by UK notified bodies.

Click here to view the updated guidance

Click here to view the updated Q&A

European Commission (EC)

The EC published a Q&A on the concept of ‘similarity’ in relation to orphan ATMP drugs

In the European Union, 10-year market exclusivity is afforded to drugs that meet the criteria described in Orphan Regulation No 141/2000. This incentive prevents the EMA from accepting an application for marketing authorisation “for the same therapeutic indication, in respect of a similar medicinal product”. Last month, the EC published the Commission Regulation (EU) 2018/781 on the concept of ‘similarity’ in relation to orphan drugs. The document aims at setting the limit of market exclusivity. This month, the EC published a Questions and Answers (Q&A) document regarding the assessment of ‘similarity’ in relation to ATMPs which may be elgible for orphan designation.

The document covers the following relevant areas:

  1. Does the route of administration play a role in the assessment of similarity?
  2. In the case of ATMPs, differences in the manufacturing technology can be relevant to demonstrate non-similarity between two products. What is the meaning of "manufacturing technology"?
  3. Which safety attributes are relevant for the purposes of assessing similarity between two ATMPs?
  4. Are all differences in the therapeutic sequence, viral vector, transfer system, or regulatory sequences relevant for the purposes of assessing similarity between two gene therapy medicinal products?

Click here to view the Q&A in full


EMA/FDA seek to strengthen their regulatory collaboration

EMA and Food and Drug Administration (FDA) have a long history of close cooperation in various areas of medicines development. During their two-day 2018 bilateral meeting which took place in June, EMA and FDA have reiterated their wish to further strength their continuous close collaboration and allowed to the agencies to review their cooperative initiatives as well as discuss strategic priorities for the coming years.

The topics discussed included:

  1. EU-US mutual recognition agreement (MRA) on pharmaceutical inspections on good manufacturing practices (GMP). The MRA came into operation in November 2017. The agreement allows the recognition of each other’s inspection outcomes of manufacturing sites for human medicines and hence better use of inspection expertise and resources. The plan for the agreement to be operational in all EU MS by 15 July 2019. Currently, the MRA covers 14 MS.
  2. ATMPs. Both agencies recognise the great potentials of ATMPs but face the same regulatory challenges and agree to encourage early parallel scientific advice to support a common scientific approach on the regulation of these medicines and post-market data collection.
  3. Real-World Evidence (RWE). EMA/FDA agreed that RWE holds major promise to strengthen decision-making on medicines throughout their lifespan. The two agencies will regularly exchange information and work together to address methodological and practical challenges in analysing this type of data.

Click here to view EMA’s press release.


Food and Drug Administration (FDA)

CBER launches INTERACT, new program for early interaction with biologics developers

Food and Drug Administration's (FDA) Center for Biologics Evaluation and Research (CBER) announced the launch of a new program for early meetings with biologics developers.

The new program, called INTERACT (INitial Targeted Engagement for Regulatory Advice on CBER ProducTs), replaces the existing pre- pre-investigational new drug (IND) meeting program for all products regulated by CBER. The INTERACT meeting, which is broadly comparable to the EMA’s Innovation Task Force (ITF) and MHRA’s Innovation Office (IO), could include a wide range of development-related topics such as requirements for preclinical testing of a product, aspects of manufacturing required for first–in–human trials, initial clinical development strategies, device or assay design considerations.

The new program is aimed at enhancing input to biologics developers at early stages of development and supporting sponsors to plan their development programs to gather evidence needed for FDA approval more effectively. Additional details related to INTERACT meetings will be provided by the FDA in the upcoming months.

Click here to view FDA press release.

2018 CBER Science Symposium

CBER held its 2018 symposium at the end of June. The purpose of this symposium was to discuss scientific topics related to the regulation of biologics and highlight science conducted at the CBER by showcasing how scientific research informs regulatory decision making and to provide a forum for developing collaborations within FDA and with external organisations. The agenda included sessions on “Immunogenicity and Immunotherapy” and “Advances in Regenerative Medicine”. All video are available on the FDA website.

Click here to access to the Symposium’s video.

FDA published a draft guidance on patient-focused drug development: collecting comprehensive and representative input

As the nature of drug development becomes more targeted and as more of the new treatments address specific aspects of disease, FDA’s approach to development and regulation is becoming more patient focused. A part of its priority, the FDA published this month a draft guidance on patient-focused drug development: collecting comprehensive and representative input. The guidance is the first of a four-part series of guidance documents required under the patient-focused drug development component of the 21st Century Cures Act. The document describes how patient experience data and other relevant information from patients and caregivers can be collected and used for medical product development and regulatory decision-making. The goal is that the resulting treatments offer more of the benefits that matter most to patients.

Click here to view to the draft FDA guidance

Public consultations




Consultation period



Study supporting the Evaluation of the European Medicines Agency Fee System

02 May 2018 to 02 Aug 2018

Draft questionnaire




Consultation period



Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management

16 Nov 2017 to 18 Dec 2018

Draft guidance