Regulatory news: July 2016

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


European Commission

Study on the regulation of advanced therapies in selected jurisdictions

The document can be downloaded here.

The EC published findings from a comprehensive study for the US, Canada, Japan and South Korea with regard to: advanced therapies that are already available to patients; those that are in development phase; and the regulatory frameworks governing advanced therapies in these four jurisdictions. The document can be downloaded here.

Key aspects of the study includes the scope of the advanced therapy regulation, regulation for clinical trials, marketing authorisation, manufacturing and quality requirements, post-marketing requirements, and regulatory pathways to gain access to advanced therapy treatment outside of clinical trials and to marketed products. In addition, the study includes an overview of research activities and availability of advanced therapies and, an analysis of economic aspects of the advanced therapies market in the four jurisdictions. The economic aspects includes relevant intellectual property rights legislation; incentives to support developers of advanced therapies; the average approval procedure time and time to be commercialised after approval of selected products; and a quick scan on pricing and reimbursement policies that exist in each of the jurisdictions.


Proposals to revise the guidance on first-in-human clinical trials

The European Medicines Agency (EMA), in cooperation with the European Commission and the Member States of the European Union (EU), is proposing changes to current guidance on first-in-human clinical trials to further improve strategies to identify and mitigate risks to trial participants.

A concept paper setting out proposed changes to the 2007 EMA guideline for first in human (FIH) trials has been released for public consultation; the deadline for comments is the 30 Sept 2016. The current EMA guideline mainly addresses the non-clinical aspects of drug development and reflects the practice at the time it was developed, which focused on a single ascending dose design for FIH trials. Since then, integration of the non-clinical data available before FIH administrations and the PK, PD and human safety data emerging during a trial has evolved. Consequently, many FIH trials are now performed with integrated protocols potentially combining different study parts. This concept paper outlines aspects to be considered in revising the current guideline to address the evolution of FIH clinical trials protocols. These changes are outlined in a new concept paper which has been released for public consultation. Click here for more details.

Statement on the outcome of the EU referendum

The European Medicines Agency (EMA) acknowledges the outcome of the referendum of 23 June 2016.

EMA would like to underline that its procedures and work streams are not affected by the outcome of the referendum. The Agency will continue its operations as usual, in accordance with the timelines set by its rules and regulations. The EMA staff will continue their mission to protect human and animal health and ensure access to medicines that are safe, effective and of good quality.

Regarding the future of the agency’s location, the agency welcomes the interest of some member state to host the agency, post-brexit. The agency has state that the future location of the EMA will be decided in due course by the representatives of the member states.

Click here for details.

Strengthening interaction with academia

EMA held a workshop on the 15 June 2016 with representatives from academia to explore new ways to engage with academics and researchers. The objectives of the framework included enhancing academia’s understanding of the EU medicines regulatory framework and increasing regulators’ understanding of the needs and expectations of academia. The outcome of the discussion will contribute to the development of the framework which will be presented to EMA’s Management Board for adoption at its December 2016 meeting. Click here for more details.



27-28 Sept 2016: The EDQM is organizing an international conference to mark the publication of the 9th Edition of the European Pharmacopoeia (Ph. Eur.), effective from 1 January 2017 and available now. The 2-day conference will include two plenary sessions and four workshops on Setting pharmacopoeial standards for biotherapeutic products; New technologies and their potential impact on monographs; The control of elemental impurities; International harmonisation. Click here for details

The EDQM has been granted Observer status to International Council for Harmonisation (ICH). Details here



Early access to medicines scheme

MHRA report the number of applications made to the early access to medicines scheme for the promising innovative medicine (PIM) designation and the scientific opinion. They also show the number of applications that have been granted and refused as well as the number of pending applications. Click here for details


Draft GxP data integrity guidance produced for industry and is open to comments. This consultation document provides guidance on the data integrity expectations that should be considered by organisations involved in any aspect of the pharmaceutical lifecycle or GLP studies regulated by MHRA. The guidance is intended to be a useful resource on the core elements of a compliant data governance system across all GxP sectors (good laboratory practice, good clinical practice, good manufacturing practice, good distribution practice and good pharmacovigilance practice). It addresses fundamental failures identified by MHRA and international regulatory partners during GLP, GCP, GMP and GDP inspections; many of which have resulted in regulatory action. Deadline for comments: 31 October 2016. Click here for details

EU referendum

The MHRA updated a statement on the outcome of the EU referendum on the 15 July 2016. The key message is that it is business as usual. Click here for the statement

Clinical trial applications and named contact updates

Effective from 27th June 2016, persons other than the applicant named in the trial application form, who call or email the MHRA CTU, and who report to be from the sponsor/applicants company, know the EudraCT number and security word/phrase (previously provided to MHRA by the named applicant) for a trial may obtain information on that trial. For ongoing studies, the applicant named in section C.1 of the application form should notify the Clinical Trials Unit of their chosen security word/phrase. They should email with the Subject line as ‘Clinical Trials named contact’ and list the EudraCT number(s) in the body of the email. For new applications, the applicant named in section C.1 of the application form is requested to include the security word/phrase in the cover letter for the submission. Click here for details

Device news

A number of manufacturers who have a CE mark for a re-manufactured single-use device (SUD) want to put them on the market in the UK. These companies have been re-manufacturing SUDs for a number of years and such devices are widely used in some countries. Over the last 3 years, the MHRA has carried out a detailed review of re-manufacturers, assessing their technical, regulatory and clinical processes. Following the review, the MHRA has developed a guidance document on the re-manufacture of Single-use devices and expectations around their use. Single-use means that the medical device is intended to be used on an individual patient during a single procedure. It is not intended to be reprocessed and used on another patient. The single-use device should either be discarded, or if appropriate, returned to a re-manufacturer of single-use devices. Re-manufacturing is where a company obtains a CE mark for the re-manufacturing of single-use devices. Click here for details


HTA 2015/16 annual review launched: 'New science, new challenge’

The HTA launched its annual review publication for 2015/16: ‘New science, new challenge”. The publication highlights the challenges faced in this time of significant and accelerating scientific advancement and how the HTA can work to create the right regulatory approach in response to these developments. The focus of the launch publication was to highlight the HTA’s work in the last year including revision of the HTA Codes and Standards and make further improvements to their guidance, improve public understanding of the HTAs work through the newsletter and working collaboratively with other government health bodies to reduce regulatory burden and support innovation. Click here for details.

Click here for more details.


Response to the Regenerative Medicine report

HRA approval for existing studies and for amendments have been higher than expected but have now reduced to near-expected levels.

The HRA response to the publication of the House of Lords Science and Technology Committee’s report on Regenerative Medicine is here. The key message was that the HRA acknowledged the Committees recommendations that relate to regulation, re-iterated their aims to support innovation and commitment to working in partnership with regulators to maximise clarity and minimise burdens.



ICH M4E(R2) Guideline reaches Step 4 of the ICH Process

The revised version of the ICH M4E(R1) Guideline on Enhancing the Format and Structure of Benefit-Risk Information in ICH reached Step 4 of the ICH Process in June 2016 and now enters the implementation period (Step 5). The M4E(R2) Guideline includes greater specificity on the format and structure of benefit-risk information, harmonising the presentation of this information in regulatory submissions. The M4E(R2) is available for download under the Multidisciplinary/CTD Guideline page on the ICH website.

ICH S9 Q&As reaches Step 2b of the ICH Process

The Questions and Answers Document of the ICH S9 Guideline on Non Clinical Evaluation for Anticancer Pharmaceuticals reached Step 2b of the ICH Process in June 2016 and now enters the consultation period (Step 3). The ICH S9 Q&As are intended to facilitate the implementation of the S9 Guideline clarifying its scope as well as its interpretation and implementation. The draft S9 Q&A document is available for download on the Safety Guideline page on the ICH website. You are invited to provide comments on the draft S9 Q&A document by e-mailing the ICH Secretariat. More details under the Open Consultation page.

ICH E17 Guideline reaches Step 2b of the ICH Process

The ICH E17 Guideline on Multi-Regional Clinical Trials reaches Step 2b of the ICH Process in June 2016 and now enters the consultation period (Step 3). This new ICH Guideline is proposed to provide guidance on general principles on planning/designing Multi-Regional Clinical Trial (MRCT). The draft E17 Guideline is available for download on the Efficacy Guideline page on the ICH website. You are invited to provide comments on the draft E17 Guideline by e-mailing the ICH Secretariat. More details under the Open Consultation page.



What’s New For Biologics

Upcoming Workshops, Meetings & Conferences (Biologics)

September 8, 2016: Public Workshop; Scientific Evidence in the Development of Human Cells, Tissues, and Cellular and Tissue-Based Products Subject to Premarket Approval. The purpose of the public workshop is to identify and discuss scientific considerations and challenges to help inform the development of human cells, tissues, and cellular and tissue-based products (HCT/Ps) subject to premarket approval, including stem cell-based products. Click here for details

Recently Issued Guidance Documents

Periodic Benefit-Risk Evaluation Report (PBRER), Questions and Answers, Guidance for Industry, July 2016

The ICH guidance (PBRER) is intended to be a common standard for periodic benefit-risk evaluation reporting on marketed products among the ICH regions. The guidance introduced new concepts linked to an evolution of the traditional Periodic Safety Update Report from an interval safety report to a cumulative benefit-risk report. It changed the focus from individual case safety reports to aggregate data evaluation. In addition, the broadened scope increased the need for integrating information within the report.

So that the guidance can be implemented and interpreted in a consistent way across the ICH regions, a Working Group (IWG) was established to assist with the implementation of the guidance. The IWG has prepared this question and answer (Q&A) document to support implementation of the guidance in practice. The Q&A document is intended to facilitate practical implementation of the PBRER, including points to consider in addressing some of the more novel aspects of the new periodic safety report. Click here for details

Quality Metrics Technical Conformance Guide provides technical recommendations for the submission of quality metric data. It is intended to ensure clear expectations for industry on the submission of quality metric data as described in the Request for Quality Metrics draft guidance.

The Guide serves as the technical reference for implementation of the draft FDA guidance for industry on Request for Quality Metrics. Since publication of the Pharmaceutical CGMPs in 2004, CDER has continued to promote its vision of “a maximally efficient, agile, flexible manufacturing sector that reliably produces high-quality drug products without extensive regulatory oversight.” The draft guidance for industry on Request for Quality Metrics and this technical reference document continue FDA’s policy efforts to ensure successful implementation of CDER’s objectives. FDA expects that quality metrics calculated from data that it collects will provide objective measures that, when used with additional internal data, will provide the Agency with indicators of the effectiveness of pharmaceutical manufacturing quality systems. The goal of these measures is to assure quality drug products are available to patients. The objectives of CDER’s quality metrics program can best be achieved through collaboration and a shared understanding of standards for metric indicators and data exchange/reporting.

This Guide supplements the draft FDA guidance for industry on Request for Quality Metrics and provides recommendations about submission of information that will support the FDA’s calculation of quality metrics. Click here for details

Currently Open Consultations

European Medicines Agency

Start Date



End Date

13 Apr 2016

Draft guideline on the sterilisation of the medicinal product, active substance, excipient and primary container

13 Oct 2016

European Commission

Start Date



End Date

1 Jun 2016

Public consultation on the revision of the "Definition of Investigational Medicinal Products (IMPs) and use of Auxiliary Medicinal Products (AMPs)" (previously called "Guidance on Investigational Medicinal Products (IMPS) and Non-Investigational Medicinal Products (NIMPs))

31 Aug 2016

1 Jun 2016

Public consultation on "Summary of Clinical Trial Results for Laypersons"

31 Aug 2016

1 Jun 2016

Public consultation on "Risk proportionate approaches in clinical trials"

31 Aug 2016

1 Jun 2016

Public consultation on the revision of "Ethical Considerations for Clinical Trials on Medicinal products conducted with Minors

31 Aug 2016

28 Jun 2016

Targeted stakeholder consultation on the draft Guidelines on Good Manufacturing Practice for Advanced Therapy Medicinal Products

26 Sep 2016


Start Date



End Date

10 June 2016

Dissemination of Patient-Specific Information from Devices by Device Manufacturers

09 Aug 2016

16 June 2016

Factors to Consider Regarding Benefit-Risk in Medical Device Product Availability, Compliance, and Enforcement Decisions - Draft Guidance for Industry and Food and Drug Administration Staff

14 Sep 2016

20 June 2016

Evaluation and Reporting of Age, Race, and Ethnicity Data in Medical Device Clinical Studies

19 Sep 2016

15 Jul 2016

Principles for Codevelopment of an In Vitro Companion Diagnostic Device with a Therapeutic Product

13 Oct 2016