Regulatory news - January 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)

Report published for Conditional Marketing Authorisations (CMA) granted from last 10 years

CMA is granted to medical products with a positive risk/benefit assessment that address unmet needs and whose availability would result in a significant public health benefit. The concept foresees that limited data for initial marketing authorisation is complemented by further data generated in the imposed specific obligations, in order to bring the overall data available to a comprehensive level.

The EMA has published a report with data collected between 2006 and 2016 following 10 years experience with CMA. The report provides a data summary of the 30 medicinal products which have received a CMA including applicants, outcomes, indications and study design. One interesting aspect is that the CMA delivered has been dominated by indications in Oncology (17/30 CMAs) and Infectious disease (9/30 CMAs). The report also provides insight into failed CMA applications which is important to consider when applying for a CMA.

Molmed’s Zalmoxis and Chiesi’s Holoclar are the only ATMPs granted a CMA to date. Under the provisions of the conditional marketing authorisation, both companies will be required to complete a post-marketing study confirming the clinical benefit previously observed. The CHMP has accepted Molmed’s TK008 trial and Chiesi’s HLSTM03 trial as post-marketing confirmatory study.

Note: Glybera was approved under the Exceptional Circumstances Scheme

Click here to view the report.

Human medicines: EMA highlights for 2016

The EMA recently published a new infographic, highlighting its regulatory activity for 2016. The agency recommended 81 medicines for marketing authorisation, including 27 new active substanceswhich include two ATMPs:

Strimvelis a gene therapy manufactured from a patient’s own immature bone marrow cells that improves their ability to fight infection

Zalmoxis a cell therapy medicine for patients receiving a haploidentical haematopoietic stem cell transplant (HSCT), which contains T cells that have been genetically modified

This brings the total number of approved ATMPs to eight since the ATMP regulation was implemented.

2015 Imlygic genetically engineered oncolytic virus to melanoma

2014 Holoclar tissue engineered product’. It consists of cells taken from the patient’s limbus (at the edge of the cornea) and then grown in a laboratory so that they can be used to repair the damaged corneal surface.

2013 MACI Matrix applied characterised autologous cultured chondrocytes for the repair of symptomatic cartilage defects of the knee

2013 Provenge Autologous peripheral blood mononuclear cells activated with pap-gmcsf for the treatment of metastatic castrate resistant prostate cancer

2011 Glybera engineered copy of the human LPL gene packaged with a tissue-specific promoter in a non-replicating AAV1 vector for treatment of patients diagnosed with familial lipoprotein lipase deficiency (LPLD).

2009 ChondroCelect autologous cartilage cells (for Repair of single symptomatic cartilage defects of the femoral condyle of the knee)

Click here to view the summary infographic from EMA.



MHRA launches public consultation to develop strategy for creation of quality standards for biological medicines

The Medicines and Healthcare products Regulatory Agency is developing a strategy for the creation of pharmacopoeial public quality standards for biological medicines. This public consultation seeks input from stakeholders regarding how they are used and can be improved as well as feedback on the Agency’s draft strategy.

Click here to view the consultation.

Health Research Authority (HRA)

HRA publishes new proportionate consent guidance

This new guidance proposes new options for ICFs preparation and ways of approaching patients for consent in low risk, pragmatic trials, where the treatment is close to standard of care, using an already licensed product or is observational. The suggestion is that for these studies SIS-ICFs can be shorter and less burdensome.

One approach that can be generalised to more complexe trial is to decompose the current ICFs into multi layers documents in order to make them more patient friendly.

Click here to view this guidance.



ANSM publishes positive results following year long pilot of the Clinical Trials Regulation

The new Clinical Trials Regulation (Regulation (EU) No. 536/2014) was adopted in 2014 with the primary goal of providing more efficient, coordinated assessments for Clinical Trial Applications (CTAs) in the EU using a central portal. However there has been some delay in its implementation (aimed for 2016) due to preparation of the portal and relevant databases.

In order to prepare for enforcement of the regulation France’s Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM) began a pilot a 2015 with industrial and academic CTA sponsors as well as collaboration with ethics committees (EC).

According to ANSM, the pilot phase indicates a positive outcome for relevant stakeholders. This analysis was based on 112 CTAs reviewed from a total of 897 to the agency with an average review time of 64.3 days for final notification.ANSM welcome the positive reception for this scheme illustrated by:· Collective commitment and constructive exchanges between sponsors, the EC and the ANSM

  • Increase of sponsors’ participation (academic and industrial)
  • Strong mobilisation from voluntary ethics committees (21 out of the 39 existing) and from the ANSM

Click here to view the ANSM report.



Citing quality standards from alternative compendia

FDA’s Office of Pharmaceutical Quality published an update to clarify its position on the appropriate use of quality standards for excipients, drug substances, and drug products found in alternative compendia in place of or in addition to the United States Pharmacopeia/National Formulary (USP/NF).

The update was published in the Manual of Policies and Procedures, updated from 2007 and 2014 versions and addresses British Pharmacopoeia (BP), European Pharmacopoeia (EP) and Japanese Pharmacopeia and goes on to say that “equivalent standards have the same acceptance criteria and make use of analytical procedures based on similar principles (e.g., chromatographic, spectroscopic, titration) and performance characteristics (e.g., specificity, accuracy, precision). A standard can be considered better than a corresponding standard for a number of reasons, including narrower ranges for acceptance criteria or superior performance of the analytical procedure (e.g., improved specificity, greater accuracy)”

The applicant will be responsible for justifiying the BP, EP or JP standards used in lieu of the USP/NF and provide a copy of of the monograph / analytical procedure.

Click here to view the manual of policies.

FDA begins accepting applications for Regenerative Advanced Therapy (RAT) designations

Following December’s signature of the new 21st Century Cures Act, which described the new pathways for accelerated development of regenerative medicines, the FDA has already unveiled a new designation refereed to as Regenerative Advanced Therapy (RAT) on its website under Cellular & Gene Therapy Products.

To qualify for the designation FDA notes;

  • The drug is a regenerative medicine therapy, which is defined as a cell therapy, therapeutic tissue engineering product, human cell and tissue product, or any combination product using such therapies or products, except for those regulated solely under Section 361 of the Public Health Service Act and part 1271 of Title 21, Code of Federal Regulations;
  • The drug is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition; and
  • Preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such disease or condition

The request for RAT designation must be made either concurrently with submission of an Investigational New Drug application (IND) or as an amendment to an existing IND. Companies have to direct to FDA guidance on on Expedited Programs for Serious Conditions – Drugs and Biologics in order to help determine whether they would qualify for such a designation.



ICH working group to provide more detailed guidance for MedDRA

The Points To Consider (PtC) working group provides guidance documents for MedDRA, a standardised terminology to facilitate sharing of regulatory information internationally.

Following a concept paper endorsed by ICH Management Board in late 2016, a proposal has been made on 23rd January to expand the remit of PtC to provide more detailed guidance, examples and Q&As on topics of regulatory importance which the ICH says can include data quality, medication errors and quality issues.

The concept paper goes on to say:

“…there are certain topics where users could benefit from having more detailed information and guidance pertaining to the use of MedDRA than can be covered in the existing documents. One topic is that of data quality in regulatory submissions - both in clinical trials and postmarketing -where it is recognized that poor quality in the initial data collection and subsequent coding and analysis steps can compromise the ability to evaluate safety issues with regulated products.”

Click here to view the final concept paper

ICH reflection paper on “GCP Renovation”; Good clinical practice revisions

On 12th January 2017, ICH invited public review and comment on a reflection paper on Good Clinical Practice (GCP) "Renovation". This contains the proposal for further modernization of the ICH Guidelines related to clinical trial design, planning, management, and conduct. These changes would impact two current guidelines; ICH E8 regulation on General Considerations for Clinical Trials and further revision to E6 Guideline for Good Clinical Practice - already undergoing modernisation with the recent production of ICH E6(R2).

In the introduction to the reflection paper, the ICH outlines:

“In a February 2016 letter to ICH, stakeholders conveyed concerns that the current ICH E6 guideline fails to sufficiently recognize variations in the level of risk for participants in different types of trials and allow corresponding flexibility in managing the risks. Another major concern was related to E6’s limited scope. It was felt that a guideline entitled “good clinical practice” should more holistically address the planning and conduct of clinical trials. The proposed renovation would address these broad and important concerns through targeted revisions made to two current ICH guidelines”

Comments should be submitted to ICH before March 11, 2017.

Click here to view the reflection paper.

Public consultations




Consultation Period


Strategy for pharmacopoeial public quality standards for biological medicines

9 Jan 2017 to 10 April 2017

Draft for public consultation



Consultation Period


Labeling of Red Blood Cell Units with Historical Antigen Typing Results Draft Guidance for Industry

3 Jan 2017 to 3 Apr 2017

Draft guidance for public consultation

Considerations in Demonstrating Interchangeability With a Reference Product

Guidance for Industry

18 Jan 2017 to 20 Mar 2017

Draft guidance for public consultation



Consultation Period


Reflection on “GCP Renovation”: Modernization of ICH E8 and Subsequent Renovation of ICH E6

12 Jan 17to 11 Mar 17

Draft for stakeholder comment