Regulatory news - March 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)

EU court of justice denies EMA’s appeal to release documents on two medicines

Late last year, CGT Catapult published an update on the EMA’s launch of its online clinical trial database, where data underpinning the authorisation of new medicines in the European Union is being published as part of the access to documents initative. As mentioned in our October article, the initiative has been challenged by some companies due to the release of commercially confidential information contained within the marketing authorisation and the EMA was in the midst of appealing a ruling from the General Court of the EU, blocking the release of particular documents.

In a ruling earlier this month from the Court of Justice of the European Union, both orders brought against the EMA (by PTC Therapeutics and Intervet) were upheld. The first order halted the release of a clinical study report for PTC Therapeutics’ Translarna, a centrally authorised medicine for the treatment of Duchenne muscular dystrophy, until a judgment in the main case is delivered by the General Court. The second order had suspended the release of three toxicity studies for Intervet’s Bravecto, a veterinary medicine used to treat flea and tick infestations in dogs and cats.

As part of a statement on the EMA website, the agency stated:

“The Agency respects the orders of the Vice-President of the Court of Justice received in early March 2017 and will not release the concerned documents until the General Court rules on the main cases. […] in the meantime, EMA will continue to process requests for access to documents concerning medicinal products in accordance with the Transparency Regulation and its 2010 policy on access to documents.”

Click here to view the full press release from the EMA which also includes a link to the Translarna court case on the Court of Justice website.

European Commission

Commission adopts EU-US agreement on mutual recognition of inspections of medicine manufacturers

Each year, national competent authorities from the EU and the US Food and Drug Administration (FDA) inspect production sites of medicinal products in Europe, the US and the rest of the world, to ensure these sites operate in compliance with good manufacturing practice (GMP). After a series of transatlantic discussions, the US and EU have announced a landmark agreement to mutually recognise one another’s pharmaceutical manufacturing inspections.

This major update will allow US and EU regulators to utilise each other’s good manufacturing practice (GMP) inspections of pharmaceutical and active pharmaceutical ingredient manufacturing facilities, reducing duplicative drug inspections and lowering costs. In the EU, inspections of manufacturing sites are carried out by national competent authorities from EU Member States.

The FDA will continue to assess each EU member state authority individually and a transition phase will be in place until July 2019. Until this time, imported products will still need to be batch tested until the requirement is waived. In future, the need for an EU authority to inspect a site located in the US, or vice versa, will be limited to exceptional circumstances.

Click here to view the full text of the agreement.

Pharma Inspection Co-operation Scheme (PIC/S) criticises European Commission’s proposal for GMP Requirements for ATMPs

The PIC/S Committee, comprises representatives of PIC/S’ 49 Participating Authorities including the US FDA, Health Canada and SwissMedic as well as representatives from partner organisations such as EMA, EDQM and WHO with a stated aim of “leading the international development, implementation and maintenance of harmonized GMP standards and quality systems of Inspectorates in the field of medicinal products”.

This month, PIC/S’ published it’s letter to the EC in which it has taken a strong stance against the proposed stand-alone, ATMP GMP guideline, which was out for a targeted stakeholder consultation until September 2016.

In the letter, PIC/S writes:

“The PIC/S Committee is unanimously concerned about the impact on public health and for the safety of patients that the ATMP GMP Guideline will cause. By lowering the GMP requirements for ATMPs, the European Commission is not only exposing patients to an increased risk to their health; it is also engaging its individual and collective responsibility for any health incident (and related court action) that lower ATMP standards may occasion. We would like you to duly ponder this aspect.”

This is not the first such comment on the new GMP guidance proposed, which received comments from 53 additional stakeholders. Regarding global harmonization and consistency with other documents, the Alliance for Regenerative Medicine (ARM) published the following on it's website in September 2016:

“…the creation of a standalone document may lead to disparities in GMP standards, creating unnecessary confusion for companies with ATMP and non-ATMP product portfolios, as well as presenting challenges to the Competent Authorities at the time of inspection. In addition, ARM is concerned that for those organizations developing ATMPs that may be less experienced in GMP and licensing requirements, the existence and adherence to two separate GMP reference documents could lead to disparate practices, resulting in different quality standards.”

Click here to view PIC/S letter to the European Commission.



Guidance on common issues identified during clinical trial applications

On the 22nd March the UK Medicines and Healthcare products Regulatory Agency (MHRA) published a series of guidances on it’s website covering “common issues with validation and assessment of clinical trial applications and how to avoid them.”

The 5-part series covers the top issues related to application validation, non-clinical and clinical data, information about the product and a list of online resources for relevant guidances and standards for the topics mentioned.

From a non-clinical perspective, the most common Grounds for Non-Acceptance (GNA) relate to a lack of information about pivotal safety studies that have been submitted in support of the application and the nature of the contraceptive advice as outlined within the protocol. GNAs are also often raised because of a lack of justification for the starting dose in humans from a safety perspective. From a clinical perspective, the most common GNA relate to lack of an acceptable Reference Safety Information (RSI) section. GNAs are also often raised because of lack of information about appropriate risk mitigation strategies (including contraceptive requirements, dose escalation stopping criteria and appropriate eligibility criteria) as well unacceptable unblinding procedures in case of medical emergency.

In this release, the MHRA also goes on to mention:

“Every trial will have its own peculiarities and each is assessed on a case by case basis, which may lead to questions needing to be asked on specific areas. By the same token, sponsors who do not comply with some of the issues raised in this guidance might not necessarily receive a GNA if they have provided an acceptable scientific (safety) justification for not complying with guidance.

Click here to view the guidances.

Human Tissue Authority

Consultation on two new EU Directives – the application of a Single European Code and the Import of Tissues and Cells

The European Union (EU) has published two new commission directives on the coding and import of tissues and cells for human application.

The UK Department of Health (DH) is currently consulting on the draft ‘Human Tissue (Quality and Safety for Human Application) (Amendment) Regulations 2017’ - the regulations transposing the two new EU Directives into UK law.

Click here to view the DH consultation on the draft regulations.

Directive 2015/565/EC

The coding directive establishes a coding system to ensure the traceability of all human tissue and cells intended for human application, at all stages from procurement to final use. It requires a single European code (SEC), in a specified format, to be allocated to tissue and cells distributed for human application, including those imported from third countries.

Directive 2015/566/EC

The import directive requires establishments to be approved by the national competent authority for the import of human Tissues and Cells, sets out procedures to verify that human tissue and cells imported from countries outside the EU/European Economic Area (EEA) meets the same quality and safety standards applicable to tissue and cells procured within EU/EEA Member States.

The Directives primarily affect establishments who are licensed by the Human Tissue Authority (HTA) and the Human Fertilisation and Embryology Authority (HFEA although the HFEA will be consulting separately.

Click here to view the HTA press release on the new directives.



FDA grants its first Regenerative Medicine Designation

The 21st Century Cures Act, which was signed into US law in December, introduced a new Regenerative Advanced Therapy (RAT) designation. Since renamed the Regenerative Medicine Advanced Therapy (RMAT) designation, this announcement means that the FDA will help facilitate the efficient development and expedited review of the Humacyte’s Humacyl, an investigational bioengineered blood vessel being tested for use with dialysis patients with late-stage kidney disease.

Based on the experience from earlier FDA ‘expedited’ programs (such as Breakthrough Therapy), the RMAT designation allows for additional development support including timely advice and interactive communication with the agency, as well as proactive and collaborative involvement by senior FDA managers.

Click here to view the announcement from Humacyte.

Public consultations




Consultation Period


Strategy for pharmacopoeial public quality standards for biological medicines

9 Jan to 10 April 2017

Draft for public consultation

The Human Tissue (Quality and Safety for Human Application) (Amendment) Regulations 2017: consultation document

10 Mar to 7 April 2017

Draft for public consultation



Consultation Period


Medical Product Communications That Are Consistent With the FDA-Required Labeling — Questions and Answers

19 Jan 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 to 13 Apr 2017

Draft guidance for public consultation