Submission Of Dossier Research Articles

Dossier submission in the UK after Brexit

The withdrawal of the United Kingdom (UK) from the European Union (EU), commonly known as Brexit, occurred on January 31, 2020, triggering a transition period until December 31, 2020, during which the UK and EU negotiated their future relationship. Brexit has brought significant changes to regulatory frameworks, particularly in the pharmaceutical sector. This article examines the transition of dossier submission procedures in the UK following Brexit, focusing on the implications for marketing authorizations (MAs) and pharmacovigilance. The Medicines and Healthcare Products Regulatory Agency (MHRA) transitioned to an independent regulatory body, establishing new guidelines for pharmaceutical companies seeking MAs in the UK. Key changes in marketing authorization routes include the conversion of centrally authorized products (CAPs) to UK MAs, the introduction of the Decentralized and Mutual Recognition Reliance Procedure (MRDCRP), and the implementation of a 150-day assessment timeline for national procedures. This article compares dossier requirements before and after Brexit in the UK and highlights pharmacovigilance requirements post-Brexit, emphasizing adjustments to reporting obligations, Qualified Person for Pharmacovigilance (QPPV) responsibilities, and the establishment of UK-specific Pharmacovigilance System Master Files (PSMFs). Additionally, it addresses the dossier Module 1 administrative information requirements to provide a comprehensive overview of the changes in regulatory procedures in the UK pharmaceutical sector following Brexit. Overall, the article aims to serve as a valuable resource for industry professionals, regulatory experts, and other stakeholders seeking clarity on the regulatory changes and their implications for pharmaceutical products in the UK following Brexit.

Health-related quality of life (HRQoL) in German early benefit assessment: The importance of disease-specific instruments

IntroductionHealth-Related Quality of Life (HRQoL) data is frequently requested in early benefit assessment in Germany. To test the hypothesis that the importance of HRQoL in general and the significance of disease-specific instruments in particular has increased since the introduction of AMNOG in Germany, we analysed all early benefit assessments between 2011 and 2022. MethodsAll 793 early benefit assessments completed between 01/01/2011 and 03/11/2022 were systematically analysed. The HRQoL instruments featured in the dossier submissions were extracted for all assessments and categorized into generic and specific instruments. All G-BA resolutions were likewise assessed for consideration and acceptance of generic and specific HRQoL instruments. In addition, it was examined whether there was an association between HRQoL data and the extent of additional benefit. ResultsSince 2014 HRQoL data have continuously been submitted in 70% to 80% of assessments per year with the exception of 2022 (63%). Generally, disease-specific instruments are favoured, regarding submissions by industry but especially with higher acceptance by the G-BA in the resolution. Subgroup analyses revealed oncology as a major contributor to the submission and acceptance rates of disease-specific instruments. Disease-specific instruments were submitted in 81% of all oncology assessments and accepted in 53% of assessments. Overall, assessments with accepted HRQoL data tend to reach a higher overall benefit. Procedures with accepted HRQoL were most likely to receive a considerable benefit (31%), while for procedures in which HRQoL data were not accepted, a benefit was most often (65%) not proven. DiscussionIndustry has followed the request for submission of specific HRQoL instruments early on. Higher submission rates of specific instruments over time which at the same time meet the methodological requirements indicate that industry has learned from early assessments. A potential reason for the high submission- and acceptance rates of specific HRQoL instruments in oncology might be the particularly high relevance of HRQoL in this indication. Possible effects of changes in legislature on the future development of submission and acceptance of HRQoL data need to be monitored. ConclusionIn Germany, HRQoL has gained a relevant position in early benefit assessment over time. Overall specific instruments are favoured, regarding submissions by industry but especially through consideration by the G-BA in the resolution. Furthermore, HRQoL data can be supportive for benefit assessments, in particular to show that advantages in morbidity and/or mortality are reflected in HRQoL and not at the expense of HRQoL.

Assessment of genetically modified maize MON 89034 × 1507 × NK603 for renewal authorisation under Regulation (EC) No 1829/2003 (application GMFF-2022-3670).

Following the submission of dossier GMFF-2022-3670 under Regulation (EC) No 1829/2003 from Corteva Agriscience Belgium BV and Bayer Agriculture BV, the Panel on genetically modified organisms of the European Food Safety Authority was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application for the herbicide-tolerant and insect-resistant genetically modified maize MON 89034 × 1507 × NK603, for food and feed uses, excluding cultivation within the European Union. The data received in the context of this renewal application contained post-market environmental monitoring reports, a systematic search and evaluation of literature, updated bioinformatic analyses and a search for additional documents or studies performed by or on behalf of the applicant. The GMO Panel assessed these data for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the context of the original application. Under the assumption that the DNA sequences of the events in maize MON 89034 × 1507 × NK603 considered for renewal are identical to the sequences of the originally assessed events, the GMO Panel concludes that there is no evidence in renewal dossier GMFF-2022-3670 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on maize MON 89034 × 1507 × NK603.

Assessment of genetically modified maize MON 89034 × 1507 × MON 88017 × 59122 and 8 out of 10 of its subcombinations for renewal authorisation under Regulation (EC) No 1829/2003 (dossier GMFF-2022-9170).

Following the joint submission of dossier GMFF-2022-9170 under Regulation (EC) No 1829/2003 from Bayer Agriculture B.V. and Corteva Agriscience Belgium B.V., the Panel on genetically modified organisms of the European Food Safety Authority was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application for the herbicide tolerant and insect resistant genetically modified maize MON 89034 × 1507 × MON 88017 × 59122 and 8 out of 10 of its subcombinations, for food and feed uses, excluding cultivation within the European Union. The data received in the context of this renewal application contained post-market environmental monitoring reports, an evaluation of the literature retrieved by a scoping review, a search for additional studies performed by or on behalf of the applicant and updated bioinformatics analyses. The GMO Panel assessed these data for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the context of the original application. Under the assumption that the DNA sequences of the events in maize MON 89034 × 1507 × MON 88017 × 59122 and 8 out of 10 of its subcombinations considered for renewal are identical to the sequences of the originally assessed events, the GMO Panel concludes that there is no evidence in renewal dossier GMFF-2022-9170 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on maize MON 89034 × 1507 × MON 88017 × 59122 and 8 out of 10 of its subcombinations.

Assessment of genetically modified maize MON 810 for renewal authorisation under Regulation (EC) No 1829/2003 (dossier GMFF-2022-9450).

Following the submission of dossier GMFF-2022-9450 under Regulation (EC) No 1829/2003 from Bayer Agriculture BV, the Panel on Genetically Modified Organisms of the European Food Safety Authority was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application for the insect protected genetically modified maize MON 810, for food and feed uses (including pollen), excluding cultivation within the European Union. The data received in the context of this renewal application contained post-market environmental monitoring reports, an evaluation of the literature retrieved by a scoping review, additional studies performed by or on behalf of the applicant and updated bioinformatics analyses. The GMO Panel assessed these data for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the context of the original application. Under the assumption that the DNA sequence of the event in maize MON 810 considered for renewal is identical to the sequence of the originally assessed event, the GMO Panel concludes that there is no evidence in dossier GMFF-2022-9450 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on maize MON 810.

A Comparative Analysis of Generic Drug Assessment and Regulatory Approval in the USA, Europe and India.

The Abbreviated New Drug Application (ANDA) is used for the regulatory submission of generic drugs, which are pharmaceutical equivalents to brand-name drugs and distributed without patent protection. Different countries have their own regulatory requirements for the approval of generic drugs, enforced by authorities such as the CDSCO in India, EDQM in Europe, and USFDA in the United States. This review aims to compare the regulatory processes and requirements for generic drug approval in India, Europe, and the US, highlighting key differences and challenges. The involvement of regulatory authorities in the drug development process is crucial for expediting approval and addressing queries, helping to minimize delays. The Common Technical Document (CTD) format is employed across regions to harmonize submission requirements. This study underscores the differences in dossier submission for generics across the three regions, illustrating India's position in the global generic drug approval landscape. By comparing approval requirements, this work provides insight into the hurdles India must overcome to streamline its approval process. The ANDA allows generic manufacturers to submit bioequivalence studies, using the original innovator's safety and efficacy data. However, obtaining approval simultaneously from multiple regulatory authorities remains a challenging task. Careful review of regulatory documents by skilled personnel can reduce regulatory queries, ultimately accelerating the market launch of generic drugs. This review provides a comprehensive overview of the generic drug approval process, emphasizing the need for harmonization and improved efficiency in India's regulatory framework.

OP104 Pilot Implementation Of Health Technology Assessment Topic Prioritization In The Philippines: Lessons And Plans For Moving Forward

IntroductionThe Health Technology Assessment (HTA) Council in the Philippines carried out its process tracks while the implementing guidelines were being finalized in 2020, due to the urgent need to respond to COVID-19. Two years later, as mandated by the Universal Healthcare (UHC) law, we opened the nominations for the HTA Council’s topic priority list, which will be assessed to inform government financing decisions.MethodsWe adopted the former Philippine National Formulary System (PNFS) but set the prioritization criteria according to the decision framework stipulated by the UHC law and allowed industry submissions. We streamlined dossier completion for topics with numerous proponents, supplemented dossier deficiencies, and adjusted the timelines of crucial steps for better reach, while accounting for possible setbacks during the time periods. We satisfied the prioritization criteria using a Delphi technique at the HTA Council subcommittee and Core Committee levels in conjunction with consultations with the Department of Health and the national payer. We also shared evidence base and topic prioritization criteria scores with stakeholders during the public consultation.ResultsIn the pilot implementation, we processed a total of 140 nominations (88 complete submissions) and released the priority list in five months. After processing 31 appeals from all key stakeholder groups, the 2022 priority list covered 31 assessments based on topics from the Department of Health, the national payer, industry, hospitals, and medical societies. Although we found gaps in the set timelines, inadequacy in the prioritization criteria parameters, and the need to increase exposure of the public to the process, we were able to accommodate all stakeholder concerns and maintain flexibility in the process.ConclusionsWe need to update our HTA process guidelines, accept joint dossier submissions, and review our topic prioritization process. The changing health system landscape and transitioning of national health priorities require coordination with the Philippine Food and Drug Administration for horizon scanning, early HTA, and managed entry agreements. Finally, there is a need to create special pathways for rare disease and innovative technologies.

3.G. Round table: European Union policies: the basis for EU legislation and the case of the EU HTA regulation

Abstract Among the objectives of the European Union (EU) there is the protection and improvement of European citizens’ health. To this end, several instruments can be enacted at EU level, both of binding legal nature- such as regulations, - and not binding -. EU regulations are binding legislative acts that must be applied across all the EU member states (MS). In the context of the Ordinary Legislative Procedure, proposals are initiated by the European Commission and their development involves two more actors, namely the European Parliament, representing EU citizens, and the Council of the EU, representing EU governments. These act as co-legislators, are requested to review the proposal, and have the right to propose amendments to reach a final agreement on a joint text, often through tripartite meetings on legislative proposals between representatives of the Parliament, the Council and the Commission; these are referred to as ‘Trilogue’ meetings. The EU regulation on Health Technology Assessment (HTAR) was adopted in January 2022, and will become legally binding in January 2025. It provides a first input for the reorganisation of the pharmaceutical market across all EU strategy (Pharmaceutical Strategy). The Pharmaceutical Strategy aims to future proof regulatory frameworks; support industry in promoting research; and foster EU citizens’ access to safe, effective, and high-quality medicines that are used in diagnosis, treatment and prevention of diseases. HTA allows for evidence-informed policy- and decision-making, disentangling the comparative value of health technologies and permits for informed negotiation in terms of pricing, reimbursement and, of course, in terms of establishing priorities for procurement decisions. The HTAR framework allows to overcome specific key challenges stemming from the highly divergent and fragmented HTA procedures across EU MS, ultimately aiming to allow a more timely and equitable access to medicines, vaccines and devices, at EU level, including by allowing a more harmonised approach in terms of dossier submission for companies too. The preparatory phase for the implementation of the HTAR is underway with the establishment of the Coordination Group on HTA (HTACG) and of the HTA Stakeholder Network, the set up of a secure intranet for the exchange of information and the planning of capacity building initiatives. This workshop is intended to provide the attenders with insights into the process behind the development of EU regulation with a focus on HTA regulation and its following implementation. Key messages • European legislative acts set the framework for the protection and the improvement of European citizens’ health and for member states policies. • The EU regulation on Health Technology Assessment will foster European citizens’ access to safe, effective, and high-quality medicines, vaccines and devices and its implementation is underway. Speakers/Panelists Jose A Valverde European Commission, DG Health and Food Safety, Brussels, Belgium Amandine Garde Law & Non-Communicable Diseases Unit, Liverpool, UK Marco Marchetti Italian National Agency for Regional Healthcare Services (AGENAS), HTA unit, Rome, Italy Iñaki Gutiérrez-Ibarluzea Basque Foundation for Innovation And Research (BIOEF), Barakaldo, Spain

Comparative study of Regulatory requirement for preparation of Dossier for Registration of Veterinary Drug in US, EU and Canada

The main purpose of this article is to research the requirement of the veterinary drug dossier submission in the three countries is US, EU, and Canada and the procedure of all the three countries are different for the submission of the veterinary drug dossier and their rules and regulation are different but all the three countries follow the VICH guidelines in these articles all the information available like necessary documents timeline approval procedure are different for US, EU, and Canada.

Strategies for deploying triple artemisinin-based combination therapy in the Greater Mekong Subregion

BackgroundThis is a qualitative study to identify implementation challenges for deploying triple artemisinin-based combination therapy (TACT) in the Greater Mekong Subregion (GMS) of Southeast Asia and to explore strategies to overcome these challenges.MethodsIn-depth interviews were conducted in three countries that have repeatedly been confronted with ACT failures: Cambodia, Vietnam, and Lao PDR. Thirty-nine key stakeholders in the healthcare systems in these countries were interviewed. One participatory workshop was conducted in Cambodia, where scenarios for potential TACT deployment were discussed.ResultsThe results section is organized around four strategic themes that emerged from the data: policy support, data and evidence, logistics and operation, and downstream engagement. The study revealed that countries in the GMS currently rely on ACT to eliminate Plasmodium falciparum malaria by 2025. TACT is, however, considered to be a useful backup strategy in case of future treatment failures and to prevent the re-establishment of malaria. The study showed that a major challenge ahead is to engage decision makers and healthcare providers into deploying TACT, given the low case incidence of falciparum malaria in the GMS. Interview respondents were also skeptical whether healthcare providers would be willing to engage in new therapies for a disease they hardly encounter anymore. Hence, elaborate information dissemination strategies were considered appropriate and these strategies should especially target village malaria workers. Respondents proposed several regulatory and programmatic strategies to anticipate the formation of TACT markets in the GMS. These strategies include early dossier submission to streamline regulatory procedures, early stakeholder engagement strategies to shorten implementation timelines, and inclusion of TACT as second-line therapy to accelerate their introduction in case they are urgently needed.ConclusionsThis paper presents a qualitative study to identify implementation challenges for deploying TACT in the GMS and to explore strategies to overcome these challenges. The findings could benefit researchers and decision makers in strategizing towards potential future deployment of TACT in the GMS to combat artemisinin and partner drug resistance.

Establishing a core dossier for multiple regulatory submissions: a case study in the Latin America region.

The Latin America region comprises several countries that do not follow harmonized regulatory requirements for drug product (DP) marketing authorization applications (MAA), resulting in customized registration dossiers for each country. Here, we established a core dossier for multiple MAA in the Latin America region by examining the similarities between regulatory requirements and reconciling their potential discrepancies through discussions among all national regulatory representatives. The core dossier was used in the submission of a new small molecule, NME1, to nine markets. Assessment of the process included the time to submission; the timing, number, and complexity of questions received; and timing of final national regulatory agencies (NRA) evaluation decisions. The core dossier resulted in an accelerated submission timeline for most markets and earlier receipt of NRA queries from some markets, compared with projections. One round of queries of a low or medium complexity was received from all agencies. The receipt of final NRA evaluation decisions was also accelerated in most markets, compared with the best-case approval timeframes. The core dossier approach was also evaluated against the standard submission of a similar small molecule, NME2. In contrast to the core dossier submission of NME1, a second round of questions, and high-complexity questions were received from two markets for NME2. In conclusion, a core dossier has the potential to simplify the regulatory process for both reviewers and applicants in regions that do not share harmonized regulatory requirements, with a consequential acceleration of DP approvals.

The consistency approach for the substitution of in vivo testing for the quality control of established vaccines: practical considerations and progressive vision.

The aim of this letter is to share the discussions and proposals made by the VAC2VAC consortium on how to support the deployment of the "Consistency Approach" for quality control of established vaccines and thus facilitate the substitution of in vivo testing. This work answers specific questions about " what does a control strategy according to the consistency testing look like" and " how to submit a control strategy defined according to the consistency testing". Some topics were answered in a very straightforward manner. This was the case when the deployment of the consistency approach and the corresponding changes in vaccines control strategy was supported by the generic application of procedures already described in regulatory guidelines/requirements and related to the establishment or change in the control strategy of vaccines. The application of other procedures required more specific attention and some were deeply debated before reaching a proposal. The key outcomes of this work are that robust science must be used to develop a substitution strategy and generate supportive data packages. And this good science can best occur with good scientific collaboration between the different parties involved. Therefore, early interaction between manufacturers and competent authorities before and during dossier submission is critical to success. The consistency approach, when approved and in place, will ensure vaccine products of assured quality reach the patient in a more efficient manner than when relying on in vivo testing. Adapting the mindset was one of the major hurdles to a progressive vision but there is now consensus between manufacturers and competent authorities to foster the elimination of in vivo testing for routine vaccine release testing.

PD63 Impact Of Parallel Submission On The Rollout Time and Health-Technology-Assessment Recommendation Of New-Active-Substances

IntroductionAustralia and Canada have parallel submission processes that allow companies to submit their dossier to the respective Health-Technology-Assessment (HTA) body before the market authorization is issued, aiming to provide timelier access to drugs. The objective of this study is to investigate the associations of parallel submissions with the rollout times and HTA recommendations of new active substances (NASs).MethodsPublic data from 208 HTA appraisals were collected from the Pharmaceutical Benefits Advisory Committee (PBAC) from Australia and the Canadian Agency for Drugs and Technology in Health (CADTH) for NASs obtaining regulatory approval between 2012 and 2020. We implemented multivariable logistic and linear regression models allowing for type of submission (parallel or sequential) and jurisdiction (Australia and Canada) to examine associations with first HTA recommendation (positive and positive with restrictions vs negative) and rollout time (regulatory submission to HTA recommendation), respectively.ResultsA total of 121 appraisals followed a parallel submission. The therapeutic products that most used a parallel submission were antineoplastic agents (Anatomical Therapeutic Chemical Code=L;47.11%). A similar proportion of chemical and biotechnological products followed parallel submissions.Multivariable linear regression showed that parallel submission presented 14-months decrease in rollout time when compared to sequential (p<0.001). Regarding jurisdictions, longer rollout times were seen for Canada when compared to Australia (β:4.0, p-value=0.024).Parallel submission showed no association with HTA recommendation. Canada had higher odds of receiving a positive recommendation (Odds Ratio:4.84, 95% confidence interval:2.63-9.18) when compared with Australia (p<0.001).ConclusionsAntineoplastic agents were the main products using parallel submissions. Appraisals following a parallel submission showed a considerably faster rollout time than those following the traditional sequential submission, illustrating the advantage of this approach for dossier submission. The submission type did not have an impact on the HTA recommendation, indicating that although quicker, the HTA decision was not affected. Canada has a more restrictive criteria regarding the timing of dossier submission compared to Australia, which may lead to disparities in their rollout time.

OP59 The Tunisian Guidelines For Pharmacoeconomic Analysis: What We Need To Know

IntroductionAs a new milestone in health technology assessment (HTA) implementation in Tunisia, L’Instance Nationale de l’Evaluation et de l’Accréditation en Santé (INEAS)—the Tunisian HTA body—published a set of methodological guidelines to support HTA dossier submission by the pharmaceutical industry. Including, ‘guide for submitting clinical data for an HTA at INEAS’, ‘methodological choices guide for pharmacoeconomic analysis at INEAS’, and ‘methodological choices guide for budget impact analysis at INEAS’. We aim to report the major methodological recommendations of the pharmacoeconomic analysis guideline.MethodsThe ‘methodological choices for pharmacoeconomic analysis at INEAS’ guideline was reviewed and the major recommendations were retrieved and reported.ResultsThe reference analysis required by INEAS is the cost-utility analysis systematically combined with a cost-effectiveness analysis (cost per life-year gained) from the public payers’ perspective. The choice of any other type of analysis must be duly justified. Comparators should include alternative treatments which are considered to be ‘the standard of care’ (i.e., interventions routinely used in Tunisia for the same indication) and in which public resources are invested. The time horizon should be sufficiently long to reflect all differences in costs and outcomes. Additionally, a discount rate of 5 percent per year is recommended. The best available evidence for efficacy, safety and quality of life is required. An indirect measure of patient preference, through a validated measurement instrument is preferred for utility calculation. Cost inputs should be identified from Tunisian sources. Health resource utilization should reflect the care pathway in Tunisia. INEAS favors the use of a recognized model. Uncertainty and impact of the input parameters on the results should be assessed and reported through probabilistic and deterministic sensitivity analyses. Model validation tests to assess face validity and internal validity should be performed, and a discussion of the methods used provided. Demonstration of external validity is required. Results should be presented in incremental cost-utility and cost-effectiveness ratios.ConclusionsThe recommendations of ‘methodological choices for pharmacoeconomic evaluation at INEAS’ is an important step to facilitate and harmonize pharmaceutical companies’ submissions and to enhance the use of these analyses in decision-making.

Assessment of the effectiveness and efficiency of the West Africa medicines regulatory harmonization initiative by the member countries.

Background: The West Africa Health Organization launched the West Africa Medicines Regulatory Harmonization Project (WA-MRH) in 2017 with the overarching objective to improve the availability of high-quality, safe and effective medicines and vaccines by the 15 countries in the Economic Community of West African States region. Although this project has made significant progress towards the realisation of its goals, challenges still remain. The aims of this study were to evaluate the effectiveness and efficiency of the WA-MRH, examine what challenges are being encountered and identify strategies that would strengthen the process for realising the initiative's goals. Methods: The Process Effectiveness and Efficiency Rating (PEER) questionnaire was used to collect data from assessors representing the seven active NMRAs in the joint assessment procedure that identified the benefits, challenges and recommendations for improving the performance of the WA-MRH project. Results: The benefits of the joint assessment procedure include time savings to manufacturers resulting from submitting one dossier and the same response package to multiple countries resulting in access to the multiple African markets within the same timeframe. Additionally, some of the NMRAs have been able to strengthen their technical capacity as a result of this initiative. Key challenges to the project include the lack of a robust information technology system that would enable dossier tracking and constraints in human resources needed to support dossier submissions and the assessment process. Conclusion: This study identified the strengths of the WA-MRH initiative as well as strategies for improvement and achievement of its objectives. The centralised submission of a dossier and its tracking is key to the regulatory assessment process. This research has demonstrated that amongst other considerations, a robust information technology system, coupled with the necessary human resource capacity would greatly enhance the effectiveness and efficiency of the WA-MRH initiative.

Review on: Dossier submission in the European countries by using mutual recognition procedure and decentralized procedure

There is different procedure used to submit drug product for marketing authorization process. Mutual recognition procedure (MRP) is one of them. The European commission had published the procedure in consultation with competent authorities of member state. Using MRP, the applicant can apply for marketing authorization in one or more European Union nations. (MAH) who already holds authorization for a medical product in a EUROPEAN UNION (EU) member state can use the mutual recognition method to get authorization in additional EU member states. Directive 2004/27/EC established the decentralized procedure. Because the mutual recognition mechanism is also reliant on national authorities recognizing a first assessment done by one-member state, the distinction is that it only applies to pharmaceutical products that do not yet have a marketing authorization at the time of application.

The consistency approach for the substitution of in vivo testing for the quality control of established vaccines: practical considerations and progressive vision

The aim of this letter is to share the discussions and proposals made by the VAC2VAC consortium on how to support the deployment of the “Consistency Approach” for quality control of established vaccines and thus facilitate the substitution of in vivo testing. This work answers specific questions about “what does a control strategy according to the consistency testing look like” and “how to submit a control strategy defined according to the consistency testing”. Some topics were answered in a very straightforward manner. This was the case when the deployment of the consistency approach and the corresponding changes in vaccines control strategy can be supported by the generic application of processes already described in regulatory guidelines/requirements and related to the establishment or change in the control strategy of vaccines. The application of some other processes required specific attention while others were deeply debated before reaching a proposal. The key outcomes of this work are that robust science must be used to develop a substitution strategy and produce supportive data packages. And this good science will be more efficient when supported by scientific collaboration between the different parties involved. Therefore, early interaction between manufacturers and competent authorities before and during dossier submission are key elements to success. The consistency approach, when approved and in place, will ensure vaccine products of assured quality reach the patient in a more efficient manner than when relying on in vivo testing. Adapting the mindset was one of the major hurdles to a progressive vision but there is now a consensus between experts from industry and regulatory bodies to foster the elimination of in vivo testing for routine vaccine release testing.

POSA325 A Comprehensive Overview of the First Educational Trainings According to New HTA Guideline for Medicines in Ukraine

The success of the HTA function in any country highly depends on raising awareness with respect to the goals and methods of conducting HTA. The study aims to give a comprehensive overview of the new educational initiative which includes training programs for pharmaceutical companies developed by the leading HTA experts of HTA Department of State Expert Center of the Ministry of Health of Ukraine. Comprehensive review of the first developed HTA training programs based on the HTA Guideline “The state health technology assessment for medicines” approved by the Order of MOH No.593 on 29 March, 2021 was conducted. In 2021 four training sessions were developed according to the provisions of the HTA Guideline and reflect harmonized international recommendations and approaches to HTA training programs, ISPOR short courses in particular, EUnetHTA, NICE, ICER, AOTMiT guidelines. Leading HTA experts of the HTA Department conducted 2-hour webinars and 7-hours seminars titled “HTA as a tool for assessing the value of health technology”. Developed programs differ by duration and cover core topics that can be adapted to the particular needs of the audience. Main components of the programs include HTA Roadmap in Ukraine, clinical section, economic section and practical case studies of building a Markov model with the help of Excel or TreeAge Software. In order to assess the quality of each program, it includes questionnaires at the beginning and in the end which gives presenters - faculty the possibility to trace progress and transform the training material accordingly, as well as a chance for the audience to give their feedback. Development of extended capacity building programs in HTA for users and doers is highly perspective for further steps in HTA institutionalization in Ukraine. It helps to overcome key challenges and highlight main solutions to optimize the process of dossier submissions.

Outcome of the public consultation and other activities to update the scientific guidance for the submission of dossiers on food enzymes

The European Commission mandated the European Food Safety Authority (EFSA) to update the scientific guidance for the submission of dossiers on food enzymes in May 2020. EFSA created a Working Group to prepare the draft document, which was critically reviewed by representatives from six Member States. The draft guidance was then endorsed by the EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP Panel) for a public consultation via the EFSA webpage. The public consultation was open for eight weeks from March 8th until May 9th 2021. At the onset of the public consultation, two webinars were organised to enhance the clarity of two topics, namely, requirement for toxicological studies and food enzyme intake model. The draft guidance received written comments from six interested parties and an individual citizen. After the public consultation EFSA organized a stakeholder workshop to publicly address the written comments and to clarify technical and procedural aspects of dossiers submission. At the end, the updated scientific guidance for food enzymes was adopted by the CEP Panel on 15 September 2021 and published in the EFSA Journal. This technical report contains the written comments received during the public consultation and explains the way they have been considered. It reports also all the engagement activities carried out by EFSA to receive input from interested parties during the development of the guidance.

Scientific Guidance for the submission of dossiers on Food Enzymes.

Following a request from the European Commission, EFSA developed an updated scientific guidance to assist applicants in the preparation of applications for food enzymes. This guidance describes the scientific data to be included in applications for the authorisation of food enzymes, as well as for the extension of use for existing authorisations, in accordance with Regulation (EC) No 1331/2008 and its implementing rules. Information to be provided in applications relates to source, production and characteristics of the food enzyme, toxicological data, allergenicity and dietary exposure estimation. Source, production and characteristics of the food enzyme are first considered only for enzymes of microbial origin and subsequently for those enzymes derived from plants and for enzymes from animal sources. Finally, the data requested for toxicology, allergenicity and dietary exposure applies to all food enzymes independent of the source. On the basis of the submitted data, EFSA will assess the safety of food enzymes and conclude whether or not they present a risk to human health under the proposed conditions of use.