Regulatory and HTA engagement – Decision Tool
Innovation Task Force
The EMA’s Innovation Task Force (ITF) provides an opportunity for academics, researchers, and SMEs to meet with EMA staff and scientific committee members for informal discussions about their research activities. The discussions can focus on scientific, legal and regulatory aspects relating to the development of new medicines or new scientific approaches that might be used during drug development or approval (e.g. biomarkers, modelling and simulation, or novel clinical trial methodology). The aim of ITF meetings is to facilitate discussions and to identify what other, more formal regulatory procedures might be appropriate for the technology under development.
PRIority MEdicines scheme
The PRIME designation is intended for medicines that meet certain criteria, such as addressing unmet medical needs and possibly oﬀering substantial beneﬁts to patients. The manufacturers of drugs that are accepted into the PRIME scheme receive early support from the EMA. This can include discussions with the EMA on data collection plans to facilitate the earliest appropriate patient access. Drugs that have a PRIME designation also receive accelerated assessment.
SMEs are deﬁned by the EMA as pharmaceutical companies that have fewer than 250 employees and that have an annual turnover of <€50m. The EMA has a dedicated team which provides administrative, regulatory and ﬁnancial support to SMEs. This includes fee reductions for most regulatory procedures such as scientiﬁc advice and marketing authorisation applications.
The EMA oﬀers an accelerated assessment process with shorter assessment times for drugs that meet certain criteria, such as those that are a major interest for public health or aimed at addressing unmet medical needs. The assessment time for marketing authorisation is reduced from 210 days to 150 days or less for accelerated assessments.
Qualification of Novel Methodologies
The QoNM procedure is a type of scientific advice offered by the EMA. It is also possible to request parallel consultations with the FDA or HTA bodies through EUnetHTA. The QoNM procedure allows a regulatory assessment of methods and tools that are intended to be used in drug development (e.g. new biomarkers, disease models, etc). The procedure is available to pharmaceutical companies, research consortia, networks, or public-private partnerships. The result of the QoNM is either a ‘qualification opinion’ or ‘qualification advice’:
- ‘Qualification opinion’ on the acceptability of a proposed new method/tool, based on the assessment of protocols, study reports and supportive data.
- ‘Qualification Advice’ on draft protocols and development plans relating to a proposed method/tool, based on the evaluation of scientific rationale and preliminary data.
Qualification advice/opinion is taken into consideration during the Marketing Authorisation Application.
Scientific Advice & Protocol Assistance
Scientific Advice enables drug developers to ask questions about their evidence development plans and clinical trial designs. The aim of scientific advice is to ensure that evidence generation plans can support marketing authorisation applications and HTA submissions for new drugs.
Several regulatory agencies and HTA bodies provide scientific advice, including the EMA, national regulatory agencies, and HTA bodies.
EMA Scientific advice
The EMA provides scientific advice and protocol assistance on the best methods for generating evidence to demonstrate the quality, safety and efficacy of a medicine. Advice is provided by responding to specific questions from the manufacturer on aspects including quality, trial design and data analysis. Manufacturers can request scientific advice at any stage of a drug’s development and regardless of whether it is eligible for authorisation under the centralised procedure offered by the EMA.
Protocol assistance is a specific type of scientific advice relating to the criteria for marketing authorisation of orphan drugs.
Scientific advice is also offered for post-authorisation safety studies which may be required as part of the authorisation of a medicine or which developers may voluntarily choose to undertake.
National regulatory agencies
Manufacturers can choose to request scientific advice on the scientific and regulatory aspects relating to the development of a medicine from a national regulatory agency in order to gain the perspectives of individual EU member states.
Further details of national regulatory agencies can be found here: https://www.ema.europa.eu/en/partners-networks/eu-partners/eu-member-states/national-competent-authorities-human.
The EMA and FDA (US regulatory agency) offer a parallel scientific advice procedure. This enables manufacturers to receive advice on particular scientific issues based on the requirements and perspectives of both regulatory agencies.
Joint national regulatory agencies-HTA
Manufacturers can request joint advice from a national regulatory agency and HTA body. Examples of countries that offer joint national scientific advice:
A number of HTA bodies offer scientific advice procedures, providing manufacturers with feedback on the country specific clinical (e.g. comparator choice relevant to the national healthcare system) and economic HTA evidence requirements. Advice is available in a number of countries (England (NICE), Germany (G-BA), France (HAS) and Sweden (TLV)) and varies in terms of scope, timescales and costs.
Parallel scientific advice from the EMA and EUnetHTA (provided by national HTA bodies) enables manufacturers to incorporate the evidence requirements for marketing authorisation and reimbursement into their drug development plans. There are 2 pathways available for this procedure:
- EMA-EUnetHTA parallel consultation: the recommendations of all HTA bodies are consolidated.
- Individual parallel consultation: the recommendations from participating HTA bodies are provided individually.
EUnetHTA – Multi-HTA
Multi-HTA scientific advice, coordinated through EUnetHTA, enables manufacturers to request feedback on their drug evidence generation plans from multiple HTA bodies simultaneously.
Mechanism of Coordinated Access
The Mechanism of Coordinated Access (MoCA) pilots provide an opportunity for manufacturers/consortia to engage in informal discussions with payer organisations and patients about the development of orphan medicines and rare disease therapies. Manufacturers can come to MoCA at any stage of a product’s development to identify and discuss potential barriers to access, such as pricing and reimbursement. Discussions are voluntary, non-binding and free-of-charge.
HTA guidance for submissions
The process/methods for HTA vary across different bodies. Further guidance is published on the websites of individual HTA agencies (e.g. HAS (France), EUnetHTA, NICE (England), NCPE (Ireland), NoMA (Norway)). During the assessment process, there may be opportunities to engage with the relevant HTA body regarding any questions or issues relating to the evidence submission. For example, manufacturers can request preliminary discussions with the Zorginstituut (The Netherlands) for advice on the data to include in the submission dossier. NICE (England) offers manufacturers the opportunity to discuss key issues during the 60‑day submission preparation stage of the appraisal. The NCPE (Ireland) also holds pre-submission meetings with manufacturers to provide support prior to finalising submission documentation.
Informal HTA advice on market access and evidence outcomes
Manufacturers should consider informal engagement with HTA bodies when developing a market access strategy, particularly around understanding the value proposition of new technologies being developed. The NICE Office for Market Access (OMA) facilitates engagement meetings between manufacturers and relevant healthcare system stakeholders to support market access planning.