Regulatory news: October 2016

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


European Medicines Agency (EMA)

Clinical Trial Transparency: New reports Go Live

On the 20th October, EMA announced the launch of an online database where clinical trial data underpinning the authorisation of medicines in the European Union will be published as part of the Transparency Regulation. EMA has said it will include the clinical overview, summary and study reports (CSRs), including data from several appendices (protocol and protocol amendments, sample case report forms and documentation of statistical methods) for all marketing authorization applications, so-called Article 58 procedures, as well as applications for new indications and variations to already-approved drugs. It is the first regulator to proactively publish CSRs from companies.

There are currently clinical reports for two drugs uploaded in the database, Kyprolis (approved in the EU in 2015 for multiple myeloma) and Zurampic (approved in the EU in 2016 for hyperuricemia). EMA is working through a backlog of reports for marketing authorisation applications, after allowing the industry including pharma, biotech and academia to get its data organised since the policy came into effect on the 1st January 2015. Currently, EMA expects to publish 4,500 clinical reports per year, all of which must be reviewed and redacted to mask both commercially confidential and patients' personal data.

The EMA press release adds that “this is will be a learning curve for the Agency and all its stakeholders, as they start to apply the policy for the first time. While the policy gives an unprecedented proactive access to clinical data, it also demands the highest standard of protection of patients’ personal data. The process will evolve over time as more experience is gained and may lead to adaptations of EMA’s guidance”.

Due to the potential release of commercially confidential information, the access to documents initiative has been challenged by some companies and the EMA was recently blocked from releasing two CSRs by orders from the President of the General Court of the European Union until a further final ruling is given by the General Court. The cases have been appealed by EMA.

The database can be found at

Click here to view the EMA press release.

Updated regulatory information in user guide for micro, small and medium-sized (SMEs) enterprises

The EMA have released an update to their user guide aimed at supporting the development of SME’s. The 92-page document provides a clear overview of the regulatory procedures available in the EU to facilitate the development of new medicines and the requirements to support a marketing authorisation across a range of product classes including ATMPs.

This update clarifies existing sections and addresses new ones related to:

  • Compassionate use: a mechanism that allows the use of an unauthorised medicine for patients with no or unsatisfactory treatment options
  • PRIority MEdicines (PRIME) procedure: a voluntary scheme to support the development of new medicines for human use that address an unmet medical need by offering enhanced early dialogue to facilitate accelerated assessment; SMEs applying for PRIME can benefit from full fee waivers on scientific advice
  • Post-authorisation measures that can be imposed at the time of marketing authorisation
  • Post-authorisation efficacy studies
  • The proactive publication of clinical data for medicinal products for human use– ‘Policy 0070’

Click here to view the user guide.

EMA maps global initiatives on medicines regulation

The first comprehensive overview of global initiatives on medicines regulation has been published by the EMA, carried out on behalf of the International Coalition of Medicines Regulatory Authorities (ICMRA). The ICMRA was formed in 2013 and consists of heads of agency leadership from across the globe with an objective to address emerging global strategic challenges to human medicine regulation.

This includes increasing complexity in medicinal products and manufacturing processes where the globalisation of the cell therapy and gene editing field (from both a research and commercial perspective) has been a strong driver, a growing number of international regulatory initiatives lacking integration and global oversight and a continued pressure to reduce regulatory public expenditures and harmonise practices.

There are a number of international regulatory initiatives which already exist including the International Council for Harmonisation (ICH) and International Coalition of Medicines Regulatory Authorities (ICMRA). The strategic direction of these initiatives, duplicated activities and participation are key topics which the ICMRA mapping project was designed to assess and concluded that “the analyses of key initiatives (multiregional, regional or thematic) showed that there is a myriad of initiatives but no strategic coordination. The focus and membership of the various initiatives are highly variable. Similar initiatives often have differently worded objectives which frequently overlap. There are some recurrent objectives e.g. information sharing and harmonisation, but they usually apply to different regions or thematic areas.”

These results have been shared as a resource for the industry and will inform future work of the ICMRA.

Click here to view the EMA’s report for the ICMRA Mapping Project.

EMA-FDA collaboration on medicines for rare diseases

On September 26th, a new EMA-FDA working group was announced aimed at sharing regulatory approaches and best practices for development of medicines in rare diseases. This will include confidential exchange of draft documents, policies under development, and more detailed information supporting the scientific basis for decision making on medicine development.

The broader goal of this particular group will be to discuss and develop;

  • Design of clinical trials in small populations and the use of statistical analysis methods
  • Selection and validation of trial endpoints
  • Preclinical evidence to support development programmes
  • Design of post-marketing studies, in the context of early access mechanisms such as EMA’s conditional marketing authorisation & FDA’s accelerated approval
  • Risk management strategies for long-term safety issues with medicines for rare diseases.

This group is similar to existing clusters between the two agencies which meet on a regular basis for collaboration on particular topics related to patient engagement, biosimilars, orphan medicines, medicines to treat cancer, medicines for children, and pharmacovigilance.

Click here to view the press release from EMA.


New EU coding platform launched

The European Commission announced a new coding platform for traceability of tissues and cells this month. The free platform is designed to help build the Single European Code (SEC) to be allocated and applied to tissues and cells.

From 29 April 2017, tissues and cells will have the SEC allocated or applied across EU member states. The information contained in the compendia is to be used when labelling tissues and cells with the SEC.

In addition, it contains two compendia:

  • the EU Tissue Establishment Compendium - this contains information about all 2800 tissue establishments authorised in the EU;
  • the EU Tissue and Cell Product Compendium – this contains categories of tissue and cell product codes.

Click here to access the EU coding platform.


EDQM enhances sharing of information with Japanese regulatory authorities and collaboration with Japanese Pharmacopoeia

The EDQM has agreed with the Japanese authorities to enhance information sharing related to therapeutic products common to both EU and Japan, and to strengthen collaboration between the European and Japanese Pharmacopoeias (Ph. Eur. and JP, respectively). The sharing of information will be primarily concerned with the outcome of GMP inspections of manufacturing sites for active pharmaceutical ingredients of interest to both Europe and Japan.

An ad hoc Technical Working Group involving staff members of the EDQM and Japanese regulatory bodies as well as relevant experts will be set up in order to share experiences and information on the development of monographs and methods of testing between the European and Japanese Pharmacopoeia.

Click here to view the press release.

2016 issue of ‘Newsletter Transplant’ now available

Volume 21 of Newsletter Transplant is now available on the EDQM website. Newsletter Transplant is published annually by the EDQM/Council of Europe and gives international figures for 67 countries on organ, tissue and cell donation and transplantation for the previous year. This work is coordinated by the Spanish National Transplant Organization (ONT), which collects and analyses the international data annually through a worldwide network of health authorities and officially-designated individuals.

Click here to view the newsletter.



Updated medical device guidance for notification of clinical investigation

As part of the process of obtaining a CE marking, medical device manufacturers may be required to carry out a clinical investigation. The MHRA recently updated its guidance regarding notification of clinical investigations for medical devices. MHRA must be informed at least 60 days before starting the investigation.

Please click here for further details on the assessment procedure and documentation required.

New guidance for class 1 medical devices

The MHRA has published its advice for manufacturers of class 1 medical devices. This includes a summary of requirements and technical documentation to provide. Reference is also made to the European Council Directive 93/42/EEC concerning medical devices.

Click here for more information on this guidance.

Latest figures on clinical trial authorisation assessments published

New figures providing total number of clinical trial applications (CTAs) and amendments received by the MHRA have been published. These have been split by phase and commercial/noncommercial sponsors) from 2005 – 2015. As expected, commercial sponsors have consistently made more CTAs than non-commercial sponsors since 2005. There was a steady decrease in the number of CTAs across all phases from 2008 until 2012 however this number has been generally increasing since 2012, led by a sharp rise in the number of phase 2/3 trials.

Click here to view this summary.

MHRA and Swissmedic sign a Memorandum of Understanding (MoU)

After a number of months of discussion, the MHRA has signed an MoU with its Swiss counterpart, Swissmedic at the 11th Summit of the Heads of Medicines Regulatory Agencies in Interlaken in October. A key pillar underpinning this formal agreement includes a shared approach to complex regulatory challenges as well as promotion of each other’s regulatory frameworks, requirements and processes.

On signing this memorandum Dr Ian Hudson, MHRA Chief Executive has said “we operate in a global environment and agreements such as these serve to further strengthen our ability to promote good practices and we look forward to working even closer with our Swiss counterparts”.

This official partnership will aim to facilitate an exchange of knowledge, and ensure regulators are better informed of new trends and challenges as well as scientific developments to better protect the health of their respective nations.

Click here to view the announcement.


BioIndustry Association publishes policy recommendations to support early-stage innovative businesses

Ahead of the chancellor’s autumn statement, the BIA has shared its proposals for the UK treasury for maintaining an innovative and internationally-competitive life sciences sector. One particular focus of this statement is on reimbursement schemes for SMEs applying to the UK’s Early Access to Medicines Scheme (EAMS). This is a voluntary procedure launched in 2014 aimed at providing patients with life threatening or seriously debilitating conditions access to medicines that do not yet have a marketing authorisation.

Click here to view the BIA policy proposals.



Organisational restructuring at FDA’s Center for Biologics Evaluation and Research (CBER)

CBER has undergone an internal restructuring effective October 16, 2016. The new CBER structure includes the Office of Blood Research and Review (OBRR), the Office of Vaccines Research and Review (OVRR), and the Office of Tissues and Advanced Therapies (OTAT, formerly known as the Office of Cellular, Tissue and Gene Therapies, or OCTGT). The formation of OTAT involves the transfer of OBRR’s Division of Hematology Clinical Review and Division of Hematology Research and Review, along with appropriate support staff, to OCTGT to constitute the new office. The products now regulated by OTAT include all purified and recombinant versions of therapeutic proteins for hematology. Antivenins have also been transferred to OTAT.



New M10 Guideline in development on Bioanalytical Method Validation

This month, the ICH endorsed a new topic on the validation of bioanalytical methods and study sample analyses in non-clinical and clinical studies. This guideline will provide recommendations on the scientific regulatory requirements for bioanalysis conducted during the development of drugs of both chemical and biological origins.

ICH Q2 Guideline on the “Validation of analytical procedures: text and methodology” has been in use for the quality evaluation of drug substances and drug products since the mid-1990s, where complex matrices are usually not included. In contrast to drug quality evaluation, preclinical and clinical bioanalysis deals with complex biological matrices such as serum, plasma or other body fluids, where variations of conditions among individuals can be quite large. In the absence of international harmonization, developers must validate bioanalytical methods and analyze samples to satisfy the requirements of the guidelines in each region, causing delays in global drug development and adding additional resource and cost burden.

A guideline specific for bioanalytical methods will be established separately from ICH Q2. The first Expert Working Group meeting on this topic will be held in November, 2016.


Presentation by Therapeutic Goods Administration (TGA) – An introduction to the work of Australia's regulator of therapeutic goods

Australia’s TGA recently uploaded a presentation providing an overview of the regulation of biologicals as well medical devices. In Australia, ‘biologicals’ is the name given to Cell and gene therapy products. Their legislative framework came into effect in May, 2011. This framework applies a risk-based system to regulation depending on how far removed these products are from their naturally occurring state (i.e. their level of manipulation) and how closely their intended use matches the natural biological function.

Click here to view the full presentation.

Public consultations



Consultation Period


Concept of 'similar medicinal product' in the context of the orphan legislation

29 July 2016 to 04 November 2016

Public consultation



Consultation Period


Requirements for quality documentation concerning biological investigational medicinal products in clinical trials

1 July 2016 to 31 December 2016

Draft guideline

Concept paper on good manufacturing practice and marketing authorisation holders

1 September 2016 to 30 November 2016

Draft Concept Paper



Consultation Period


MHRA GxP Data Integrity Definitions and Guidance for Industry

21 July 2016 to 31 October 2016

Public consultation



Consultation Period


Deciding When to Submit a 510(k) for a Change to an Existing Device

8 August 2016 to 7 November 2016

Draft Guidance for Industry and FDA Staff

Deciding When to Submit a 510(k) for a Software Change to an Existing Device

8 August 2016 to 7 November 2016

Draft Guidance for Industry FDA Staff

510(k) Third Party Review Program;

13 August 2016 to 14 November 2016

Draft Guidance for Industry, FDA & Third Party Review Organizations



Consultation Period


ICH guideline E17 on general principles for planning and design of multi-regional clinical trials

June 2016 to 31 January 2017

Draft guidance for public consultation



Consultation Period


Regulation of autologous cell and tissue products and proposed consequential changes to the classification of biologicals

21 July 2016 to 31 October 2016

Public consultation

Guidance on variations to biologicals included in the Register

30 September 2016 to 11 November 2016

Public consultation

Orphan drug program

14 October 2016 to 25 November 2016

Public consultation