Regulatory news - May 2017

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EUROPE

European Commission

Stakeholder survey; strengthening EU collaboration on Health Technology Assessment (HTA)

HTA is a used to aid decisions on the reimbursement of new medicines or recommendations for their use within a particular jurisidication. It is indepedant to marketing authorisation from regulatory agencies. The European Commission works with the European Member States to foster collaboration between HTA bodies and during October to January 2017, ran a stakeholder survey to assess stakeholder opnion of this collaborative framework.

Topics covered were diverse and a large majority of the respondents considered that EU cooperation on HTA should continue beyond 2020 (87%). Most respondants agreed that information on comparing new health technologies to previous ones should be accessible to doctors (95%) and patients (84%).

Some of the challenges to the HTA framework in Europe were highlighted in the ‘industry’ perspective within the report:

“…HTA procedures are very diverse across EU, and this diversity constitutes a hurdle for companies, as they have to adapt to various national requirements. […] there are differences regarding the starting moment (e.g. before or immediately after marketing authorisation is granted or at later stage) and length of the HTA procedures, scope of HTA (i.e. all vs a selection of medicinal products), type of assessment carried out on a regular basis (e.g. only relative effectiveness assessments/REA vs sequential clinical and economic assessments vs full HTA), data accepted (e.g. only published vs non-published data), opportunity for early dialogues, level of engagement with stakeholders, availability of relevant documents and background information, and finally the purpose and weight of assessments (e.g. recommendation vs binding opinion for pricing and reimbursement decisions)”.

Click here to view the commission’s survey.

Commission launches stakeholder consultation on European blood, tissue and cells legislation

On the 30th May, the European Commission launched an initial public consultation on Directives 2002/98/EC and 2004/23/EC relating to blood, tissue and cells legislation within the European Union to form the basis of it’s evaluation of the framework.

“The purpose of this consultation is to support a comprehensive evaluation of the Union legislation on blood and tissues and cells and their implementing (technical) Directives, examining their functioning across the EU. In particular the consultation aims to gather views on the extent to which the Directives have met their original objectives and whether they remain fit for purpose. The evaluation is expected to provide a sound evidence base which will be used to consider the need for any changes to the legislation.”

Click here to view a summary of the consultation, open until 31st May 2017.

European Medicines Agency (EMA)

Revamped EudraVigilance system given ‘green light’ for collection and monitoring of suspected adverse reactions

On the 22nd May 2017, EMA management endorsed the launch of a new pharmacovigilance system, to go live on 22 November 2017.

The new system, used by national competent authorities, marketing authorisation holders and clinical trial sponsors, includes enhanced functionality and more efficient processing which includes:

  • Simplified reporting of individual case safety reports (ICSRs) and the re-routing of ICSRs to Member States as marketing authorisation holders will no longer have to provide these reports to national competent authorities, but directly to EudraVigilance, which will ultimately reduce duplication of efforts [An ICSR provides information on an individual case of a suspected adverse reaction to a medicine];
  • Enhanced search and more efficient data analysis capabilities;
  • Increased system capacity and performance to support large volumes of users and reports (including non-serious adverse reactions originating from the EEA);
  • More efficient collaboration with the World Health Organization (WHO) as EMA will make the reports of individual cases of suspected adverse reactions within the EEA available to the WHO Uppsala Monitoring Centre (UMC) directly from EudraVigilance; Member States will no longer need to carry out this task.

Relevant users will need to ensure that this change is manged effectively and that the required IT infrastructure is in place. The EMA will support users through targeted e-learning and face-to-face trainings, webinars and information days. Users will also be able to trial the new functions of the EudraVigilance system in a test environment as of 26 June 2017.

Click here for more information on the new Eudravigilance system.

New ATMP receives positive opinion recommendation for repair of cartilage defects in the knee

On the 19th May 2017, the European Medcines Agency recommended granting a European marketing authorisation for a new advanced therapy medicinal product (ATMP) called Spherox. This was based on the recommendation from the Committee for Advanced Therapies (CAT) to the Committee for Medicinal Products for Human Use (CHMP).

Spherox is developed by CO.DON AG (based in Germany), which focusses on tissue engineered products for treatment and repair of articular cartilage and spinal disc defects. The novel product uses autologous cultured cartilage cells (chrondocyte spheroids) transplanted arthroscopically into the patient's knee where they form new tissue to heal the defect.

According to the EMA’s press release:

“The effects of Spherox were studied in two clinical trials, with patients between 18 and 50 years of age. The first study, a phase II trial, included 75 patients with cartilage defect sizes from 4 to 10 cm² and, the second, a phase III trial, involved 102 patients with defect sizes from 1 to 4 cm². The effect of the treatment was assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire which evaluates patients’ views on their knee-associated problems, such as pain, impact on daily living, sport and recreational activities, and quality of life. Statistically significant improvement of the score was seen in both studies.”

The recommended indication for Spherox is for repair of symptomatic articular cartilage defects on the femoral condyle and the knee patella; defects of up to 10 cm² for adults.

Click here to view the EMA press release.

EMA publishes its 2016 annual report; PRIME initiative highlighted

The European Medicines Agency’s (EMA) has published its 2016 annual report focusing on the Agency’s key achievements in the areas of medicine evaluation, support to research and development of new and innovative treatments as well as the safety monitoring of approved medicines. In 2016, the Agency recommended a marketing authorisation for 81 medicines, including 27 new active substances.

The report covers various facts and figures over the last year as well as the Agency’s main projects, initiatives in 2016. These include the 2016 launch of PRIME (PRIority MEdicines); a new scheme providing early and enhanced support to medicines that have the potential to address patients’ unmet needs.

84 applications were received in 2016 for the PRIME initiative in total, half coming from SMEs with the majority targeting cancer indications. Importantly, around half of the applications granted PRIME designation are advanced therapies. Of the applications which have been rejected, 70% did not contain sufficiently robust data, 40% provided insufficient justification of therapeutic advantage and 20% were too far along in development to be candidates.

As of 26 May 2017, 25 medicines have been granted PRIME, similar in it’s objectives to the US FDA ‘breakthrough therapy designation’.

The agency also highlighted its adaptive pathways approach, of interest to advanced therapy developers who are often looking at intitial treatment in small patient populations;

“Adaptive pathways can be defined as a structured approach aspiring to bring a medicine to patients in a progressive manner. Under this approach, the medicine will initially be authorised in a small patient population that is likely to benefit most from it. Then, additional evidence is gathered over time, potentially resulting in changes to the marketing authorisation reflecting the expanded knowledge acquired.”

The two year pilot project for the approach ended in 2016 and the EMA is currently exploring the concept further, particularly in the context of parallel scientific advice with HTA bodies, with the inclusion of additional stakeholders, such as patients and payer organisations. Developers are invited to submit a proposals to EMA for programmes that would be eligible.

Click here to view EMA’s 2016 report.

Patient involvement at the EMA during the assessment of benefits and risks of medicines

The EMA has published a report on the experience gained during its pilot project to involve patients during assessment of the benefits and risks of medicines. This involvement with the Committee for Medicinal Products for Human Use (CHMP) could be when assessing whether to recommend the authorisation of a new medicine or the maintenance, suspension or revocation of an existing authorisation, or a restriction of indication of an authorised medicine. Over two years, the EMA received oral patient explanations for 6 medicines treating Duchenne muscular dystrophy and multiple sclerosis amongst other indications.

“The overall feedback received from both the CHMP/EMA members and the patients involved during the pilot is very positive and reflects the usefulness and benefit of including patients within CHMP discussions when there is an opportunity to enrich the B/R discussions with a patient perspective…There was also a learning curve with each case whereby there were improvements as experience was gained, e.g. preparing more focused questions for the patient representatives, and generally everyone involved knew better what to expect.”

It has been proposed to continue to invite patients to oral explanations on a case-by-case basis when input could be valuable to the assessment, but also to use additional methods and consult patients on a more regular basis.

Click here to view the report from the EMA.

International

FDA

Comments from FDA highlight regenerative medicine development

A recent article from the Regulatory Affairs Professionals (RAPS) Society highlighted the FDA's new regenerative medicine advanced therapy (RMAT) designation, a direct outcome from the 21st Century Cures Act, and its potential impact on expediting the development and approval of cutting edge cell and gene therapies.

Peter Marks, the Director of FDA’s Center for Biologics Evaluation and Research is reported to have made the following comments on the RMAT designation at a recent Food and Drug Law Institute ‘s annual conference:

"The great part of this is this provision did not lower the safety and effectiveness standard … although we have tremendous flexibility, which we intend to use... We don't stand on ceremony—forget about the old two randomized controlled trials—single arm, compelling studies are okay in this setting”.

Two companies, Humacyte and Enzyvant, have already announced they have received the RMAT designation, and Marks said the first request for the designation came on 14 December 2016, just one day after Cures was signed into law.

On an FDA blog post from the end of March 2017, Peter Marks goes on to say that:

“We have started receiving RMAT designation requests and expect that, as with Breakthrough Therapy Designation, early and frequent communication facilitated by the RMAT designation will help reduce overall product development times. We very much look forward to continuing to work with sponsors of these products and other stakeholders to help make these exciting new therapies available to those in need.”

Click here to view the article from Regulatory Affairs Professionals (RAPS) Society.

Public consultations

EUROPEAN MEDICINES AGENCY (EMA)

 

Title

Consultation Period

Category

1.

Concept paper on the need for revision of note for guidance on quality of water for pharmaceutical use (H+V)

6 Mar t6 June 2017

Draft concept Paper

2.

Draft guideline on multiplicity issues in clinical trials

01 Apr t30 Jun 2017

Draft guideline

3.

Draft guideline on good -clinical -practice compliance in relation to trial master file (paper and/or electronic) for content, management, archiving, audit and inspection of clinical trials

12 Apr t11 Jul 2017

Draft guideline

4.

Reflection paper on statistical methodology for the comparative assessment of quality attributes in drug development

01 Apr t31 Mar 2018

Draft reflection paper

5.

Draft guideline for the notification of serious breaches of Regulation (EU) No 536/2014 or the clinical trial protocol

23 May t22 August 2017

Draft guideline

6.

Stakeholder consultation for the evaluation of EU legislation on blood, tissues and cells

29 May to 31 August 2017

Stakeholder consultation

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