Regulatory news - February 2017

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


European Medicines Agency (EMA)

Report published following December’s conference on optimising development of advanced therapies

On the 16th December 2016, the fifth annual conference conference jointly organised by European Biopharmaceutical Enterprises (EBE) and the European Medicines Agency (EMA) was held in London to discuss the challenges facing ATMP development and accelerating patient access, nearly a decade after ATMP Regulation (EC) No 1394/2007 was adopted. A range of issues were identified as obstacles to greater uptake of these treatments from a lack of sustainable funding models to insufficient transparency and regulatory guidance for companies.

For the industry, manufacturing challenges was a key topic for discussion. The report focusses on the example of an ex vivo autologous gene therapy product with a centralised manufacturing facility versus decentralised, regional manufacturing hubs, where more processes can be automated, and hones in on three aspects:

  • Vector scale-up, moving from adherent culture (small batch sizes) to fully disposable and scalable suspension platforms, eliminating the need for ongoing plasmid manufacture
  • Ex vivo cell processing, currently a manual process (extraction) requiring highly skilled operators and where scale-out needs can be significant since patient populations, particularly in oncology, can be large
  • Change management and comparability for manufacturing changes aiming to enable the treatment of larger populations.

Challenges of integrating the Environmental Risk Assessment (ERA) for EU clinical trials with GMO-based ATMPs was also raised in light of the the Clinical Trial Regulation due to be implemented in October 2018. This new regulation will harmonise clinical trial applications across the EU however it will not address ERAs for investigational medicinal products.

The report goes on to say:

“The preferred options for industry for resolving challenges resulting from different implementation across the EU Member States are having a co-ordinated ERA with one dossier via one central point, as for marketing authorisation applications, or as a minimum, having a harmonised data template, procedures and timings across Member States.”

Click here to view the full report.

EMA publishes follow-up activities to address stakeholder comments from May 2016 ATMP workshop

On 27 May 2016, the EMA hosted a workshop to foster ATMP development and enable expanded patient access in the EU by exploring solutions to challenges across a fairly diverse set of topics ranging from orphan similarity to development of patient registries and stakeholder engagement.

The report, published in early February, lists the main issues raised during the workshop as well as outcomes and the agency or group responsible for managing any actions to be taken. The proposed outputs of the workshop will be considered for a wider EU plan to be developed by EMA, CAT, the EC and the National Competent Authorities (NCAs).

The document does not contain any proposals that would require changes to the legal ATMP framework and revison of the legislation underpinning ATMPs in Europe is currently not foreseen.

Click here to view the the report.

EMA outlines GCP inspection plan for 2017

The European Medicines Agency (EMA) recently released its 2017 work plan for good clinical practice (GCP) inspections, which involves collaborating with the US Food and Drug Administration (FDA) to limit duplicative inspections.

The following key objectives will drive the working group’s agenda:

  • define in advance the number of GCP inspections to be requested in 2017
  • ensure a broad coverage of product types, therapeutic areas/indications, target populations, sponsors/contract research organizations (CROs)/vendors, studies and sites
  • proactively select the focus areas on indications, populations, geographical locations of sites, recruitment rates, size of sponsors, size of CROs and tasks and other general trends
  • ensure that diverse geographical regions are selected for inspection, including countries outside the EU from which a substantial amount of clinical trial data derives
  • ensure that GCP inspector’s resources are allocated for the conduct of routine and “for cause” GCP inspections in the context of the centralised procedure

Revisions on GCP guidelines for advanced therapy medicinal products and recommendations on the qualifications of inspectors verifying trial compliance with GCPs will be finalized in 2017.

Click here to view the 2017 work plan for the GCP inspectors group in more detail.

EMA proposes further transparency revisions regarding access to corporate documentation

The EMA is proposing a revision to its policy on accessing documents, extending its scope to include its corporate documents and increasing the publication of clinical data for pharmaceuticals. Since October 2016, the EMA has published pharmaceutical trial data for eight marketed drugs via its new website.

The revision to the European Medicines Agency policy on access to documents (POLICY/0043) takes into account the experience gained since the introduction of the policy in December 2010. It also extends the scope of the policy from pertaining to documents related to medicinal products for human or veterinary use to also pertaining to corporate documents.

EMA’s implementation of the concept of public access to documents is a two-fold approach. The first relates to the adequate follow-up to written requests for access to any document in full respect of EU legislation. The key features (i.e. classification of EMA documents, handling of initial and confirmatory applications) will be adhered to as described in the polcy. The second, is the proactive disclosure of EMA documents on the EMA website as part of broader commitment by agency to transparency. This includes information on the medicinal products and regulatory procedures for which EMA is responsible as well as agendas and minutes of the scientific committees’ meetings.

Other procedural details and definitions have also been updated.

Click here to to view the policy revision.

EMA publishes new concept paper for public consultation covering quality requirements of medicinal products containing a device component

The European Medicines Agency (EMA) has released a new concept paper for public consultation to address a need for a guideline on dossier requirements for medical devices that are supplied along with medicinal products or where a device is necessary for administration or localisation (site-specific delivery) of a medicinal product (e.g. pre-filled syringe, auto-injector).

Unlike the US, where the FDA oversees the regulation of both drugs and devices, CE marked medical devices are reviewed separately (by an accredited Notified Body) but in some cases are co-packaged with the medicinal product. As the EMA describes, “the assessment performed by the Notified Body may not fully take into account the characteristics of the specific medicinal product that the device is to be used with. This could have an impact on the overall quality, safety or efficacy of the medicinal product when used along with the specified medical device”.

The guidance will not specifically address issues related to the integral device as part of combined advanced therapy medicinal products (cATMPs as per Regulation (EC) No 1394/2007) but it is expected that the same principles will apply. However, quality issues related to devices when used for a delivery function in cATMP products will be covered.

Click here to view the concept paper.

European Parliament

EU Parliament committee backs report to increase access to medicines

The European Parliament’s committee for Environment, Public Health and Food Safety (ENVI) has backed a draft report calling on the commission to analyse the impact of intellectual property on pharmaceutical access, as well as review the regulatory framework for orphan medicines and fast-track approvals, among other provisions.

The draft document mentions a number of topics related to patient access which include:

  • Price of medicines
  • Barriers to access
  • Drug shortage
  • Research and development priorities
  • Cost transparency
  • Urgency of antimicrobial resistance threats
  • National and regional health technology assessment (HTA)
  • Harmonized criteria to assess the added therapeutic value compared with the best available alternatives

Click here to view the draft document.



MHRA announces 'regulatory ready' stem cell lines for clinical development

At the end February the UK medicines regulator published a press release announcing that the UK Stem Cell Bank (UKSCB) at the National Institute for Biological Standards and Control (NIBSC) is releasing its first stem cell lines suitable for development into novel cell-based medicines, aimed at researchers wishing to bring new and innovative therapies to clinical trial.

The stem cell lines are produced and quality-controlled under European regulations and considered qualified for use as starting materials in cell therapy manufacture. According to background information provided by the MHRA,.these stem cell lines will be produced by a handful of UK universities and deposited at the UKSCB in compliance with the quality standards described in the European Tissue and Cells Directive. In the coming months, the stem cell lines produced by the University of Sheffield, University of Manchester and King's College London will be made available, followed by additional stem cell lines from Newcastle University and Roslin Cells by the end of the year.

Click here to view the MHRA press release.

MHRA launches 2017 guides covering UK pharmaceutical regulations, EU directives and guidance

The new guides (referred to as the Orange and Green guides) are aimed at manufacturers and distributors of human medicines. The 2017 editions have been updated to incorporate changes and additions made to the detailed European Community guidelines on Good Manufacturing Practice (GMP) and the revised EU Guidelines on Good Distribution Practice (GDP).

The Orange guide contains new sections on:

  • GMP for excipients
  • Guidance on revised Annex 16 of GMP
  • Data Integrity definitions and guidance for industry

The Green Guide provides a single source of guidance to, and legislation for, the distribution of medicines in Europe and UK.

There are new sections on:

  • Guidelines on principles of Good Distribution Practice of active substances for medicinal products for human use
  • Matters relating to unlicensed medicines
  • Sourcing and exporting medicinal products – non-EEA countries
  • Data integrity
  • The EU regulation on safety features for medicines

The Orange and Green Guides are available to be ordered from Pharmaceutical Press. They are also both available online via MedicinesComplete.



Deadline for FDA's eCTD transition approaches

Beginning 5th May 2017, all pharmaceutical, biologic and generic manufacturers will have to submit to the US FDA Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) all New Drug Applications (NDAs), Biologics License Application (BLAs) and Abbreviated New Drug Applications (ANDAs) using the electronic Common Technical Document (eCTD).

The CTD is a common global standard for companies to electronically submit the quality, safety and efficacy information required for approval to the regulatory agencies in the US, EU, Canada and Japan. It was designed to make regulatory submissions easier and more efficient by implementation of a common global standard for companies to electronically submit their data.

For sponsors, eCTD submissions can be less expensive to produce and ship, provided they have business processes to accommodate the change from a paper-based format to an all-electronic one. With e-submission becoming mandatory, smaller companies, and those with fewer resources will need to ensure they can manage this transition.



ICH E11(R1) draft addendum on clinical investigation of medicinal products in the pediatric population under public consultation

Since the adoption of the ICH E11 Guideline on Clinical Investigation of Medicinal Products in the Pediatric Population in 2000, pediatric drug development has been enhanced by advancements in several areas of general adult drug development. In the last decade, targeted scientific and technical issues relevant to pediatric populations, regulatory requirements for pediatric study plans, and infrastructures for undertaking complex trials in pediatric patient populations has made significant progress, without a parallel development of harmonised guidance in these areas.

The purpose of the 15 page addendum, approved by the ICH Assembly in October 2016, is to complement and provide clarification and current regulatory perspective on the relevant topics in pediatric drug development but does not alter the scope of the original guideline.

Section 2 on ethical considerations, section 4 on age classification and pediatric subgroups (including neonates), and section 7 on pediatric formulations, supplement the content in ICH E11 (2000). Section 3 on commonality of scientific approach for pediatric drug development programs addresses issues to aid scientific discussions at various stages of drug development in different regions. Section 5 on approaches to optimise pediatric drug development includes enhancement to the topic of Extrapolation, and introduces Modelling and Simulation (M&S).

Click here to view the ICH E11(R1) draft guideline.

Public consultations




Consultation period


Strategy for pharmacopoeial public quality standards for biological medicines

9 Jan 2017 to 10 April 2017

Draft for public consultation



Consultation period


How to prepare a pre-request for designation (Pre-RFD)

13 Jan 2017 to 14 Mar 2017

Draft guidance for public consultation

Considerations in demonstrating interchangeability with a reference product

Guidance for industry

18 Jan 2017 to 20 Mar 2017

Draft guidance for public consultation

Considerations in demonstrating interchangeability with a reference product

18 Jan 2017 to 20 Mar 2017

Draft guidance for public consultation

Medical product communications that are consistent with the FDA-required labeling — questions and answers

19 Jan 2017 to 19 Apr 2017

Draft guidance for public consultation



Consultation period


ICH E11(R1) guideline on clinical investigation of medicinal products in the pediatric population: Step 2b

12 Oct 2016 to 13 Apr 2017

Draft guidance for public consultation