Regulatory news - June 2019

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


European Commission (EC)

EC Grant EU Conditional Marketing Authorisation for First Gene Therapy for Blood Disorder

Bluebird Bio announced on 3rd June that the EC granted conditional marketing authorisation for Zynteglo, a gene therapy for patients 12 years and above with transfusion-dependent β-thalassemia (TDT), a rare inherited blood disorder that causes severe anaemia. People with this genetic condition cannot make enough β-globin, meaning that patients require frequent blood transfusions. Zynteglo is used in patients who do not completely lack β-globin, and who are eligible for stem cell transplantation but do not have a matching related donor.

Zynteglo is an autologous gene therapy, consisting of the patients CD34+ cells genetically modified to encode for the βA-T87Q-globin gene, when the modified cells are given back to the patient they are transported in the bloodstream to the bone marrow where they make healthy blood cells that produce β-globin.

TDT is a rare disease and Zynteglo was designated an ‘orphan medicine’ on 24th January 2013. Zynteglo received a conditional marketing authorisation valid throughout the EU on 29th May 2019.

For more information on Zynteglo, see here.

European Medicines Agency (EMA)

EMA Offers Q&A on using OOS Batches of Authorised ATMPs

The EMA’s Committee for Advanced Therapies, together with the GMDP Inspectors Working Group and the Blood Products Working Party have released a Q&A document on how companies should go about using out of specification (OOS) batches of authorised cell or tissue based ATMPs.

The Q&A document explains how the administration of OOS batches of ATMPs may be considered to avoid an immediate significant hazard to the patient, however manufacturers must provide an evaluation of the risks to the treating physicians and notify the EMA and CA within 48 hours of administration of the OOS batch.

For more information, see here. For the Q&A document, see here.

Two Additional Countries to Benefit from EU-US Mutual Recognition Agreement for Inspections

It was confirmed on the 10th June 2019 that Luxembourg and the Netherlands have joined the mutual recognition agreement between the European Union (EU) Member States and the United States (US) Food and Drug Administration (FDA). These two EU Member States have demonstrated capability to carry out good manufacturing practice (GMP) inspections at a level equivalent to the US.

The FDA will now rely on a total of 26 Member States whose inspection results can replace their own. Currently, Germany and Slovakia are the only EU Member States yet to join the agreement, but actions for the agreement operational in all EU Member States by 15th July 2019 are progressing.

For more information, see here.

EMA to Reinstate Some Activities Halted by Brexit

Since making some progress with preparations for Brexit in transferring medicine marketing authorisations from the UK to the EU, the EMA has announced the highest priority activities to be reinstated for the remainder of 2019.

However, due to the number of agency staff expected to leave as a result of the new headquarters being located in the Netherlands, the EMA have noted that most activities will remain on hold, including guideline development, some working party meetings and proactive publication of clinical data.

The activities to be reinstated include projects aiming to increase the efficiency of the EMAs operations, key public health priorities including availability of medicines and the restarting of some EU network working groups.

For more information, see here. For the list of activities the EMA has prioritised, see here.


Food and Drug Administration (FDA)

FDA Tries to Prep Stem Cell Clinics for Upcoming Enforcement

In November 2017, the FDA launched a comprehensive regenerative medicine framework and announced that until November 2020, the agency will exercise enforcement discretion for certain human cells, tissues and cellular and tissue-based products (HCT/Ps) when the use of the product does not pose potential significant safety concerns. Since the framework was announced, progress by regulated industry coming into compliance has been slow.

In light of this, the FDA has introduced the temporary TRG Rapid Inquiry Program (TRIP). TRIP will operate as part of the FDA’s Tissue Reference Group (TRG), in order to help manufacturers of HCT/Ps obtain a rapid, preliminary, informal, non-binding assessment regarding how the specific HCT/P is regulated. The programme will run from 12th June to 31st December 2019.

To read the full article, see here. For further information on TRIP, see here.



Update from the ICH Biannual Meeting

At the International Council for Harmonisation (ICH) biannual meeting in Amsterdam from 1st – 6th June, the ICH Assembly agreed to work on four new topics for ICH harmonization, including:

Q5A(R2) Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of human or Animal Origin - proposed as an update to expand the scope of the guideline to include new biotech products such as viral-like particles and viral-vectored particles.

E6(R3) Guideline for Good Clinical Practice - revision to address the increasing diversity of study types and data sources used to support regulatory and health policy decisions in line with the ICH reflection paper on GCP renovation.

E2D(R1) Post Approval Safety Data Management: Definition and Standards for Expedited Reporting – proposed to incorporate “pragmatic potentially risk-based approaches of the management of information from existing and any new data sources, to enable a greater focus on the data sources that will optimize signal detection activities and public health”.

A new Guideline on Non-clinical Biodistribution Studies for Gene Therapy Products, which will “recommend types of nonclinical studies with which collection of biodistribution data is considered informative and/or necessary to support dosing in early clinical trials, and which will provide guidance on the design of the studies. This will result in streamlined development of the gene therapy products with higher scientific rigor while minimizing the unnecessary use of animals”.

The ICH reported this was the largest biannual meeting to date and this demonstrates the efforts being made to encourage harmonization.

For the full report on the ICH Biannual Meeting, see here.

China Food and Drug Administration (CFDA)

China Tightens Genetic Material Rules

From 1st July 2019, China will be enforcing a new set of tighter standards on the use of human materials, including DNA, organs, blood and tissues. The new standards require foreign organisations intending to use human genetic materials to collaborate with local partners in order to obtain samples, and otherwise place limits on the access they have to samples taken in China. Foreign organisations, individuals and institutions will be prohibited from collecting human genetic resources in China and from distributing resources overseas. Fines will apply if organisations and their local partners do not comply with the restrictions.

The report is part of a wider effort to reduce duplication and increase harmonisation among drug regulators from the US, Europe, Japan and elsewhere, and includes the topic of horizon scanning for new innovations, which for most regulators is still in its infancy. In addition, the report addresses novel regulatory pathways, such as expedited and other early engagement pathways with stakeholders such as the Health Technology Assessment agencies.

To read the full article, see here. The report is available here.

Public consultations


[1] Only applicable to ATMPs where a device is considered part of the container closure system. The guideline does not apply to combined ATMPs



Consultation period


ICH guideline E8 (R1) on general considerations for clinical studies

10 May to 30 Sept 2019

Public consultation