Regulatory news - October 2019

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


European Medicines Agency (EMA)

MolMed Withdraws Conditional Marketing Authorisation for Zalmoxis Cell Therapy

Zalmoxis was conditionally approved in June 2016 to treat patients with high-risk blood cancers. The cell therapy was an add-on treatment for adults who had received haematopoietic stem cell transplants (HSCT).

MolMed said it decided to withdraw after taking into account the “overall results of the interim analysis voluntarily carried out by the company as part of the review of the product development plan, as well as the interactions with EMA in the latest months”.

See here for official press release and the here for the European Public Assessment Report from the EMA.

European Commission (EC)

EC Releases Final Adopted Guidelines on Good Clinical Practice for ATMPs

The EC has published the final Guidance document on Good Clinical Practice (GCP) for ATMPs. The guidelines have been adopted after a period of public consultation with stakeholders in 2018. The Guidelines will not replace the ICH GCP guidance but will serve to give additional guidance specific to ATMPs.

See here for the final guidance document.

EC Publishes a Good Practice Document for GMO Requirements in Clinical Trials

The EMA has published a Good Practice document on the assessment of GMO related aspects in the context of clinical trials with AAV clinical vectors to improve the interplay between GMO and pharma legislation. It gives guidance on what should be included in the Environmental Risk Assessment (ERA) for clinical trials with AAV vectors, such as potential hazards to human health and the environment, likelihood of adverse events linked to the vector, accidental transfer of the AAV to non-target individuals, transmission through shedding and risk management strategies.

The EMA has also published a common application form for contained use and deliberate release of medicinal products containing AAV clinical vectors to accompany the guidance. Both documents have been endorsed by 17 Member States.

See here for guidance.

The EC Publishes an Evaluation of the EU Blood, Tissues and Cells Legislation

The Blood, Tissues and Cells (BTC) legislations were developed to ensure public health protection for all stages of procurement and testing processes for BTC substances, defining minimum quality and safety standards at Union level and aiming to facilitate increased exchange of BTC substances between Member States.

The Blood Directive (2002/98/EC) adopted in 2002, and the Tissues and Cells Directive (2004/23/EC) adopted in 2004 have been assessed for effectiveness, relevance, efficiency, coherence and EU‑added value. The evaluation concluded the following:

  • The legislation effectively increased the level of safety and quality for BTC across the EU;
  • Many of the current rules are no longer up to date with the dynamic BTC sectors;
  • Key oversight requirements were not adequately specified to ensure robust oversight of the BTC sectors;
  • Some groups, such as donors are not adequately protected;
  • The legislation does not keep in pace with innovation;
  • Provisions are limited to help achieve sufficiency and continuity of supply.

The results of the evaluation were discussed at a conference on the 28 October 2019 in Brussels and the EC have published the Commission Staff Working Document on their website.

See here for the evaluation.


Medicines and Healthcare products Regulatory Agency (MHRA)

MHRA Updates Clinical Trial Authorisation Guidance Due to Update in End of Trial Legislation

The MHRA has made changes to the end of trial section for their “Clinical trials for medicines: manage your authorisation, report safety issues” guidance.

The legislation only requires global end of trial to be submitted but there is also a facility to inform the MHRA when a trial ends in the UK. The MHRA will no longer acknowledge local end of trial notifications, but still expect to receive relevant safety updates and substantial amendments for an ongoing trial until a global end of trial notification is received.

If an exemption to this requirement is needed, this can submitted as a substantial amendment for approval.

For more information see the guidance here.

MHRA Guidance and Publications About a Possible No-deal Brexit

The MHRA has published a series of guidance documents for industry and stakeholders.

The Agency are continuously updating their guidance about a possible no-deal Brexit; no major updates have been made this month. There have been minor changes to the following headings:

  • Marketing authorisations, variations and licensing guidance
  • Medicines for children

To view the guidance, see here.



US Food and Drug Administration (FDA)

FDA Revises Guidance on Drug Master Files

The FDA have revised their guidance on drug master files (DMFs). DMFs contain all confidential information about facilities, manufacturing, processing, packaging and storing drugs. This is the first revision since its publication in September 1989.

The update includes more detailed instruction on submitted original DMFs versus amendments, a reference to the electronic submission requirements and more guidance on the format and delivery of DMFs.

See here for the draft guidance document.

Pharmaceutical Inspection Co-operation Scheme (PIC/S)

PIC/S Revises GMP Guide Annex 2 (Manufacture of biological medicinal substances and products for human use)

PIC/S have revised Annex 2A (Manufacture of Advanced Therapy Medicinal Products for Human Use) and 2B (Manufacture of Biological Medicinal Substances and Products for Human Use) and have invited stakeholders to comment.

The revisions for Annex 2A consider international developments in the regulation of ATMPs and accommodates for technological change in future.

See here for the consultation and here for the revised Annex.