Regulatory news - November 2017

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


European Commission (EC)

New guidelines on Good Manufacturing Practice (GMP) specific to Advanced Therapy Medicinal Products adopted by the EC

A new GMP guideline adapting current European GMP requirements has been published by the EC. This guideance outlines requirements specific to GMP manufacturing of ATMPs which have been granted a marketing authorisation as well as those used in a clinical trial setting.

The latest guidance was first released for public consultation in 2016 as part of a joint action-plan launched by the Directorate General for Health and Food Safety (DG SANTE) of the European Commission and the European Medicines Agency (EMA) based on Article 5 of Regulation 1934/2007 (the ‘ATMP’ regulation).

The guidance aims to foster a risk-based approach to manufacture and testing of ATMPs which ‘permits the manufacturer to design the organisational, technical and structural measures that are put in place to comply with GMP -and thus to ensure quality according to the specific risks of the product and the manufacturing process’.

This approach is aimed to be reflective of technological advancements in the field which are often developed in an academic or hospital setting under quality systems different to those typically utilised for the manufacture of conventional pharmaceuticals. However, there has been some concern within the industry that the creation of a standalone guidance document may lead to disparities in standards, creating confusion for companies as well as challenges to inspection by the Competent Authorities.

In a letter signed by PIC/S (Pharmaceutical Inspection Co-operation Scheme) Chairman Paul Hargreaves of the UK’s Medicines and Healthcare Regulatory Agency and Deputy Chairman Boon Meow Hoe of Singapore’s HSA, some concerns on regulatory equivalency were raised:

"Your decision to amend Annex 2 and repeal Annex 13 of the EU [PIC/S] GMP Guide is a serious setback in terms of co-operation between the EU and PIC/S. It is very unfortunate that under your leadership the process of GMP harmonisation between the EU and PIC/S GMP Guides has resulted in a divergence that may be difficult to reconcile in the future".

Currently, these new technologies must comply with general GMP guidelines set out in Volume 4 of The rules governing medicinal products in the European Union. However from 22 May 2018, ATMP manufacturers will need to ensure they are compliant with the new Part IV of EudraLex Volume 4.

Click here to read the new ATMP GMP guidelines.

EC closes public consultation on the definition of orphan drug ‘similiarity’ in relation to ATMPs

In 2016, the EC launched a public consultation on the concept of ‘similarity’ in relation to orphan drugs – a concept which sets the limit of market exclusivity in the European Union. The 10-year orphan exclusivity afforded by Regulation No 141/2000 prevents the EMA from accepting an application for marketing authorisation “for the same therapeutic indication, in respect of a similar medicinal product.”

Commission Regulation No 847/2000 defines the concept of “similar medicinal product” which is especially important to define for ATMPs given their composition and manufacturing process and the fact that many target rare diseases. The 2016 consultation was aimed at updating the definition in light of scientific and technical progress that has taken place over more than 15 years since its implementation.

Following public comments received and follow-up ATMP workshops at the agency a further update was a released for consultation. For ATMPs, it provides the following definitions:

“(3.1) Cell-based ATMPs: Two related cell-based medicinal products are not similar if:

- there are differences in starting materials or the final composition of the product which have significant impact on the biological characteristics and/or activity relevant for the intended therapeutic effect of the product. The different source of the starting materials (e.g. as in the case of autologous ATMPs) is not sufficient to support a claim that two products are non-similar; or

- there are differences in the manufacturing technology having a significant impact on the biological characteristics and/or activity relevant for the intended therapeutic effect of the product.

(3.2) Gene therapy medicinal products: Two gene therapy medicinal products shall not be considered similar when there are differences in the therapeutic sequence, viral vector, transfer system or regulatory sequences that significantly affect the biological characteristics and/or activity relevant for the intended therapeutic effect of the product.

Differences in the therapeutic sequence without a significant impact on the intended therapeutic effect are not sufficient to support the claim that two gene therapy medicinal products are non-similar.

(3.3) Genetically modified cells. The considerations under (3.1) and (3.2) apply.

A summary from the first wave of public responses received between July and November 2016 can be found on the website of the European Commission.

Click here to view the latest draft regulation from the European Commission.

European Medicines Agency (EMA)

EMA headquarters will move to Amsterdam in 2019

The European Medicines Agency (EMA) will relocate to Amsterdam in 2019 following the United Kingdom’s decision to withdraw from the European Union. The location was decided on 20th November 2017 by 27 Member States in the European Council. The EMA has been based in London since it was established in 1995 and currently employs nearly 900 staff members at its headquarters in Canary Wharf, London.

EMA staff indicated that Amsterdam ticked many of its boxes for relocation. The agency’s Executive Director Guido Rasi said in a statement that “[Amsterdam] offers excellent connectivity and a building that can be shaped according to our needs. I am very grateful that the Member States took into account our requirements for business continuity and gave priority to the protection of public and animal health.”

Following this announcement, the EMA also recently published practical guidance on the procedure for Brexit supported by a Q&A document. Some of the clarifications include:

  • As of 30th March 2019, the UK will become a “third country”
  • Marketing authorisations and orphan designations currently held by UK entities must be transferred to a legal entity in the EEA
  • QPs, QPPVs and PSMFs must continue to be located in the EEA
  • Grouping Brexit related variations will be possible in certain scenarios
  • Variation categories are defined for certain changes to manufacturing, EU QC testing and batch release sites

Click here to view the EMA’s press briefing on its relocation to Amsterdam.

Guidance and Q&A to support companies in their move following Brexit can be found on the EMA website.

Novartis submits a Marketing Authorisation Application (MAA) for Kymriah

Following its recent submission to the FDA to extend Kymriah’s indication to r/r DLBCL, Novartis announced its MAA submission to the European Medicines Agency (EMA) this month for treatment of children and young adults with relapsed or refractory (r/r) B-cell acute lymphoblastic leukemia (ALL) and adult patients with r/r diffuse large B-cell lymphoma (DLBCL).

Whilst it has not been officially announced whether Kymriah will have an ‘accelerated assessment’ at the agency which would reduce the assessment timeframe to 150 days from up to 210 days, this is expected given that Kymriah (CTL019) has already been granted PRIME designation and orphan status in Europe as well as having a priority review in the US in the lead up to approval.

Novartis’ MAA submission is based on the multicenter, phase II ELIANA and JULIET trials, conducted in collaboration with Penn. These two global trials examined patients across 27 centers in the US, Canada, Australia, Japan and the EU including Austria, Belgium, France, Germany, Italy Norway, Spain and The Netherlands.

Click here to view the press release from Novartis.

United Kindgom (UK)

Government announces new accelerated access scheme

A new, fast-track route into the UK National Health Service (NHS) for “breakthrough” medicines and technologies was announced by the Government last month in response to the independently chaired Accelerated Access Review (AAR).

The new Accelerated Access Pathway is expected to go live in April 2018 and is aimed at dramatically speeding up the time it takes for patients to benefit from ground-breaking therapies. Similar to breakthrough therapy / RMAT designation in the US, and PRIME in Europe, under the UK scheme a number of products would receive “breakthrough” designation each year, unlocking a comprehensive package of support that will allow firms to accelerate clinical development and benefit from a fast-track route through the NHS’s approval processes.

Whilst official guidance is still to be announced, the new pathway is likely to include:

  • Streamlining the pathway from market authorisation through to patient use for designated products
  • Support in the generation of real-world evidence, in addition to clinical trials data
  • Early price negotiation and the potential for flexible and confidential commercial arrangements

Click here to view the full story on the UK government website.



FDA launches policy framework for regenerative medicines

Last month, the FDA announced a new policy framework for regenerative medicine advanced therapies (RMAT) through release of two draft and two final guidance documents. This new framework was eagerly anticipated by the industry, based on previous statements by FDA Commissioner Scott Gottlieb as well as legislation announced in the 21st Century Cures Act.

The final guidance documents clarify when cell and tissue-based products are exempt from the established regulations and how the FDA interprets “minimal manipulation” and “homologous use.” These factors are not only important in determining what regulations must be considered by developers but also the products which could be eligble for regulatory benefits.

The first draft guidance relates to the evaluation of devices used in combination with regenerative medicine advanced therapies. The second, describes the expedited programs that may be available to sponsors of regenerative medicine therapies in the US, including the new RMAT Designation, Priority Review, and Accelerated Approval.

The guidance specifically describes the products that may be eligible for RMAT designation which include cell therapies, therapeutic tissue engineering products, human cell and tissue products, and combination products using any such therapies or products, as well as gene therapies that lead to a durable modification of cells or tissues (including genetically modified cells).

As part of the guidance document, FDA has also published a help comparative table including below, which highlights some of the differences between the already exisiting Breakthrough Therapy Designation and the latest RMAT designation at the agency.

Click here to view the press release from FDA, including all new draft and finalised guidances.

Public consultations



Consultation Period



Reflection paper on statistical methodology for the comparative assessment of quality attributes in drug development

01 Apr 2017 to 31 Mar 2018

Draft reflection paper




Consultation Period



Breakthrough Devices Program - Draft Guidance for Industry and Food and Drug Administration Staff*1

25 Oct 2017 to 24 Dec 2017

Draft guidance