Submission Of Dossier Research Articles

Pricing and Reimbursement of Patent-Protected Medicines: Challenges and Lessons from South-Eastern Europe.

Efficiency and transparency of pricing and reimbursement (P&R) rules and procedures as well as their implementation in South-eastern Europe (SEE) lag substantially behind Western European practice. Nevertheless, P&R systems in SEE are rarely critically assessed, warranting a detailed and wider-encompassing exploration. Our study provides a comparative assessment of P&R processes for patent-protected medicines in ten SEE countries-EU member states: Croatia, Slovenia, Hungary, Romania and Bulgaria; and non-EU countries: Albania, Montenegro, Serbia, North Maceodina, Bosnia and Herzegovina. P&R systems are compared and evaluated through a research framework that focuses on: (1) public financing of patent-protected medicines, (2) definition of benefit packages, (3) requirements for the submission of reimbursement dossiers, (4) assessment and appraisal processes, (5) reimbursement decision making, (6) processes that occur post reimbursement, and (7) pricing. The study aims to contribute to the discussion on improving the efficiency and quality of P&R of patent-protected medicines in the region. We conducted a non-systematic literature review of published literature, as well as policy briefs and reports on healthcare systems in the SEE region along with legal documents framing the P&R procedures in local languages. The information gathered from these various sources was then discussed and clarified through structured telephone interviews with relevant national experts from each SEE country, mainly current and former senior officials and/or executives of the funding and assessment/ appraisal bodies (total of 20 interviews conducted in late 2019). Capacity building through sharing knowledge and information on successful reforms across borders is an opportunity for SEE countries to further develop their P&R policies and increase (equitable) access to patent-protected medicines (especially expensive medicines), increasing affordability and containing costs. Simple yet robust and systematic decision-making frameworks that rely on international health technology assessment (HTA) procedures and are based on the pursuit of transparency seem to be the most cost-effective approach to strengthening P&R systems in SEE. Further reforms aiming to develop transparent and robust national decision-making frameworks (including oversight) and build institutional HTA-related and decision-making capacity are awaited in most of SEE countries, especially the non-EU members. In non-EU SEE countries, these efforts could increase access to patent-protected medicines, which is-at the moment-very limited. The EU-member SEE countries operate more developed P&R systems but could further benefit from developing their procedures, oversight and value-for-money assessment toolbox and capacity, hence further improving the transparency and efficiency of procedures that regulate access to patent-protected medicines.

Drug Prices and Value of Oncology Drugs in Italy

ObjectiveThe main objective of this study was to evaluate the potential role of efficacy data and other information available at the time of price and reimbursement (P&R) decision-making process within the definition of oncology treatment costs in Italy. MethodsThe study included all P&R dossiers submitted to the Italian Medicines Agency between July 2015 and December 2017. It prospectively collected the data of the P&R process starting from dossier submission up to the Italian Health Service reimbursement decision. The cost of treatment per patient was estimated using both the list price (“gross cost”) and the confidential net price (“net cost”) of drug packages and applied to the median duration of treatment. A 2-sample stage Heckman decomposition model was used to evaluate the potential role of efficacy data and other information available at the time of P&R decision making on the gross and net cost. ResultsA total of 37 oncology drugs related to 58 therapeutic indications were analyzed. The multivariate model showed that the variation of progression-free survival is the only variable predictor statistically associated with treatment cost, but this effect was observed only when confidential net prices were used (P=.026). ConclusionsConsidering the perspective of a developed country having a public healthcare service with a central reimbursement negotiation is determined a relevant reduction in the treatment cost purchased by public payers. This is a useful approach to guarantee the affordability of innovative oncology drugs and to contain public expenditures on healthcare. Furthermore, the negotiation of confidential discounts and agreement clauses in managed entry agreements seemed to reward oncology drugs displaying an added therapeutic benefit.

PNS45 Pricing and Reimbursement of Innovative Medicines: Challenges and Lessons from South-Eastern Europe

While Western European states sustain comparatively generous pharmaceutical benefit packages, less affluent South-eastern European countries (SEE) face substantial challenges in keeping pace with financing innovative (usually expensive) medicines. Pricing and reimbursement (P&R) processes present one of those challenges. The purpose of the study is twofold. First, it aims to provide a concise yet in-depth comparative overview of the procedures and rules governing the P&R of innovative medicines in the SEE region. Second, it seeks to contribute to the discussion on improving the outcomes of P&R by comparing and studying the successes and failures of contemporary national P&R processes and therefore contribute to reducing hurdles to equal, generous and timely access to new innovative medicines for all citizens. Data were collected from non-systematic literature review (including policy-related sources) and interviews with national experts from ten SEE countries. P&R systems are compared and evaluated through a research framework that focuses on: 1) public financing of innovative medicines, 2) definition of benefit packages, 3) requirements for the submission of reimbursement dossiers, 4) assessment and appraisal processes, 5) reimbursement decision making, 6) processes that occur post reimbursement and 7) pricing. All stages of P&R processes in SEE countries would benefit from relying on clearly defined rules, procedures and processes. Due to the lack of financial resources, low institutional capacities and few experts in the Health Economics field, it seems unwise to suggest that SEE P&R systems should be strengthened by developing extensive and sophisticated Health Technology Assessment (HTA) processes. Simple yet robust and systematic decision-making frameworks (including guidelines, scorecards, checklists, consensus building methodologies, etc.) which rely on international HTA procedures and are based on the pursuit of transparency seems as a more cost-effective approach to strengthening P&R systems in South-east Europe.

Administrative guidance on submission of dossiers and assessment reports for the peer‐review of pesticide active substances and on the maximum residue level (MRL) application procedure

This document provides guidance to applicants submitting dossiers related to the approval of pesticide active substances and for setting of maximum residue levels, and to Member States preparing assessment reports on active substances within the scope of Regulation (EC) No 1107/2009 and Commission Implementing Regulation (EU) 2020/1740, or evaluation reports on maximum residue levels applications, within the scope of Regulation (EC) No 396/2005. It describes the administrative requirements for the preparation and submission of the dossier to support an application for the approval, the amendment of approval or the renewal of an existing approval of a pesticide active substance, and for maximum residue levels,for applications submitted as of 27 March 2021.It also describes the support initiatives available from the preparation of the application (pre-submission phase) to the adoption and publication of EFSA's output. The Transparency Regulation amended the General Food Law by introducing new provisions in the pre-submission phase and in the application procedure: general pre-submission advice, specific aspects for intended applications for renewal (notification of intended studies, including their design, public consultation on the intended studies, renewal pre-submission advice by EFSA), notification of information related to studies commissioned or carried out to support an application, public disclosure of non-confidential version of all information submitted in support of the application and related confidentiality decision-making process, public consultation on submitted applications. These new requirements, as implemented by the Practical Arrangements laid down by EFSA, are reflected in this guidance. The guidance describes the procedures and the associated timelines for handling applications related topesticide active substances. Itprovides additional instructionsand guidance to applicants and rapporteur Member States, and co-rapporteur Member Stateswhere relevant, with the aim to enhance the quality of applicationdossiers and assessment reports. The document also provides guidance to applicants and Evaluating Member States on applications for the setting of maximum residue levels, in particular concerning the provisions introduced by the Transparency Regulation amending the General Food Law and their implementation in the procedure for such applications,according to the Practical Arrangements laid down by EFSA.

Implementation of Quality by Design (QbD) Principles in Regulatory Dossiers of Medicinal Products in the European Union (EU) Between 2014 and 2019

BackgroundQuality by Design (QbD) is a systematic risk-based approach to development, with predefined characteristics and quality risk management throughout the life cycle of a product. International Conference on Harmonization (ICH) guidelines Q8–Q11 give guidance on QbD applications with ICH Q8 (R2)—approved in 2009—describing the principles of QbD in detail. Since its adoption over 10 years ago, more information about QbD usage for the development of medicinal products is expected to be written in regulatory dossiers by companies.MethodsThe present study set out to evaluate the implementation of QbD principles and elements in all EU approved marketing applications (MA) (n = 494), based on information available in the European Public Assessment Reports (EPARs), for a period of six years (2014–2019), starting 5 years after QbD adoption.ResultsOf the 494 MAs, 271 were submitted with a full dossier (article 8(3)). According to EMA (38%), out of the 271 full dossier submissions, only 104 were developed using full QbD. This figure did not increase during this period. Interestingly, between 2014 and 2019, several MAs were not developed via full QbD implementation but used one or more QbD elements during development, including design space. In addition, a higher percentage of small molecule products were developed with QbD as opposed to biotechnology-derived products (78% vs. 22%, respectively).ConclusionOverall, QbD during development of medicinal products is still not commonly described in dossiers. However, more companies started mentioning QbD elements, thus making it a promising step toward QbD as the standard for development in the future.

Strategies and Approaches of Companies in Portugal and Spain in Complying with the REACH Regulation

The implementation of the Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) regulation had been viewed to be the most ambitious chemicals legislation in the world and had placed a great challenge among the European Union (EU) member states. While government regulatory agencies were focused on how they can successfully implement and enforce the legislation, the industries’ concern was to guarantee the compliance with the regulation. Despite the progress, implementation of the regulation still experienced significant problems in the quality of the information provided by companies in their registration dossiers. Given that the success of the REACH process depended primarily on the adequate and reliable information supplied by industries, there was a need to document and manage the knowledge gained and generated since its implementation. Data from survey questionnaires revealed that major issues and concerns identified by industries consisted of communication problems among participants in the implementation of the Substance Information Exchange Forum (SIEF), failure to reach an agreement on the sharing of existing data, testing cost and lack of response from suppliers in the use of substance and correction of errors in the safety data sheet. To address these issues and concerns, the European Chemicals Agency (ECHA) implemented the SIEF for EU-based chemical industries to form consortiums and jointly carry out registration and dossier submission. Participants identified SIEF as the best practice enabling companies to complete their registration and dossier submission, as well as the most efficient method in complying with REACH regulation.

PNS266 Collecting EARLY Access Real World Evidence DATA for a Successful Reimbursement Appraisal

In France, patients benefit from early access to innovation, ahead of the marketing authorization approval, via the compassionate use program (ATU). Medicinal products indicated in a severe, rare and/or chronic disease are likely to be eligible mainly when there is no suitable treatment available and when both efficacy and safety are relevant. ATU approval is associated with a data collection protocol (PUT). Real world data (RWD) have to be collected during ATU. HTA agency is resquesting ATU data during the reimbursement assessment. We investigate how ATU data are valuated by the Transparency Commission (TC) in France. We performed a retrospective analysis of TC assessments published on the HAS website in 2019. We read and collected information about how these ATU data were value in the reimbursement appraisal. Amongst the 130 TC evaluations reviewed, 18 products were available in an ATU program (50% being onco-hematology drugs). For 90% of the products, the TC concluded clinically relevant comparator(s) exist(s). 78% of the ATU products were valued with a medical improvement rating (ASMR IV [minor] or better). The median target population was very low: 51 years (min-max: 0-1679) The data valued by the TC were: patients’ characteristics and clinical outcome, efficacy, safety and prescription data (treatment line, prescribers, etc.). All of these data were displayed for only 2 products. For these 2 products, the TC valued the data collected. Collecting ATU data allows to gather early real world evidence data, which are an asset for successful market access. Those data are considered as valuable by TC and mentioned in the apraisal. The challenge is to optimize the collection of relevant ATU data for market access considering the short time available to set up an ATU, and TC dossier submission mandatory deadlines.

PRO59 ANALYSIS OF THE G-BA BENEFIT ASSESSMENTS OF ORPHAN DRUGS AND GERMAN PAYER OPINIONS ON THE NEW "LAW FOR THE IMPROVEMENT OF SAFETY IN DRUG SUPPLY"

Since 2011, manufacturers of orphan drugs with sales exceeding €50m have been required to undergo assessment by the Joint Federal Committee(G-BA). Currently, an “additional benefit” is assumed for orphan drugs by the G-BA; however, the “Law for improvement of safety in drug supply”, expected to be implemented in Jul-2019, is likely to impact the assessment. According to the Mar-2019 draft, the G-BA would be able to commit manufacturers to carry out data collection, if not enough evidence is available to assess the benefit at the time of the dossier submission. If no added benefit is demonstrated or no additional data is collected, then this can impact the to be agreed reimbursement price1. The research aimed to evaluate the rationale behind the benefit assessment ratings of orphan drugs and to explore payer’s opinions on the impact of this new law. All completed orphan drugs G-BA assessments between Jan-2011 to May-2019 were reviewed. Drugs receiving a non-quantifiable additional benefit were further studied to identify reasons behind their rating, using the G-BA justification of the resolution documentation. Furthermore, via the IPSOS Dimensions software, 38 payers in Germany were asked about their opinion on the new law, regarding orphan drugs. 115 orphan drug patient-populations were evaluated by the G-BA. 65 drugs were granted a non-quantifiable added benefit. The primary reasons observed were related to the study design, mainly the lack of a direct comparator(n=51) but also the short length of trials, small target population and lack of blinding. Moreover, the new law is expected to worsen the conditions for new orphan drug evaluations. The lack of a direct comparator was the main reason for unquantifiable additional benefit score in orphan indicated. The new law, which addresses the benefit assessment for orphan drugs, will likely add hurdles to manufacture’s developing orphan drugs, according to payers.

An Overview of the Drug Registration Requirements for Export to Tanzania, Nepal, and Cambodia.

In the semiregulated market, different countries have varying requirements of registration for export to such a specific country or region. The objective of the present study is to give a comparative overview of pharmaceutical registration requirements for export to Tanzania, Nepal, and Cambodia. In the African region especially, east Africa including Tanzania is an emerging market for pharmaceuticals. The Tanzania Food and Drugs Authority is the drug regulatory body in Tanzania and it follows the Common Technical Document (CTD) format for dossier submission. However, Nepal is still a developing country with respect to the pharmaceutical sector. The drug governing body in Nepal, Department of Drug Administration, has its own nation-specific guidelines for drug regulation, but the CTD format is also acceptable for dossier submission. In Cambodia, the Department of Drugs and Food is the drug regulatory authority that comes under the Ministry of Health of Cambodia. As Cambodia is included in the Association of Southeast Asian Nations (ASEAN) body, it follows the ASEAN CTD (ACTD) format for dossier submission.

Good Practices in Management of deficiencies in CTD dossier and comparative study for US, EU and Australia

This topic aims at reviewing the drug and drug product filing and obtaining USFDA EMEA and TGA approval and its effective role to improve the standards which are laid by them. The respective Regulatory Agency approves the new/generic drug products that govern respective market before introduction of particular product into the market. The Regulatory Agency approves the entire new drug product to be safe and effective before marketing. USFDA is the Regulatory Agency which is responsible for the regulation of food and drug product in USA. EMEA is the Regulatory Agency which is responsible for the regulation of food and drug product in Europe. TGA is the Regulatory Agency which is responsible for the regulation of therapeutic goods in Australia.
 A dossier contains detail information about the drug substance and drug product and result of studies that are carried out in development process. For getting market authorization has to be submitted to the respective regulation bodies. Due to various regulations, ICH introduced CTD for such countries that come under it. CTD is critical for dossier submission. For regulatory submission that is to be accepted in all ICH countries.
 CTD provides standardized structure. CTD makes filing easier globally. But there are differences in dossier submission requirements in these countries i.e. Module I is country specific and other regional guideline are also considered while compiling dossier application.

PNS312 QUANTITATIVE AND QUALITATIVE ANALYSIS OF THE AMNOG ARBITRATION BOARD DECISION FACTORS FOR THE PRICING OF NEW ACTIVE SUBSTANCES IN GERMANY

Since AMNOG regulation was introduced in 2011, a dossier submission to the Joint Federal Committee (G-BA) is required for the demonstration of additional benefit by new active substances over current standard of care (SoC) in Germany . After G-BA has released the results of its health technology assessment (HTA), the manufacturer enters reimbursement price negotiations with the National Association of Statutory Health Insurance Funds (GKV-SV). If the GKV-SV and the pharmaceutical manufacturer are unable to negotiate a price within six months of the HTA assessment results publication, an independent Arbitration Board mediates the price between the parties (§130b SGB V). The results of the decisions have a significant influence on all price negotiations between health insurance companies and manufacturers. The criteria influencing the arbitration decisions have yet to be systematically and comprehensively examined. Therefore, our objective is to identify and understand possible decision patterns of the Arbitration Board. All accessible written decisions of the Arbitration Board from January 2011 to February 2019 were examined (n= 43). The disputed factors between the parties were qualitatively extracted. Recurring points of contention as underlying decision factors were then subjected to a qualitative and quantitative evaluation. In our analysis, 12 factors in the arbitration process were identified to have an influence on prices. This analysis also explored how the weighting of the 12 factors varied in accordance to e.g. orphan drug status, specialty vs primary care drugs and multiple subpopulations. Arbitration decisions do not follow a rigid pattern. However, the results of this analysis provide a preliminary basis to support manufacturers in the identification of suitable analogues to inform different price strategies for the price negotiation between the GKV-SV and the manufacturer. By analyzing potential selection and decision criteria, a hypothesis for the potential arbitration decision can be derived.

Проблеми правового регулювання спрощеної реєстрації ветеринарних препаратів в Україні

Статтю присвячено дослідженню особливостей правового регулювання спрощеної реєстрації ветеринарних препаратів у світлі гармонізації законодавства України із законодавством ЄС. Відзначено, що у зв’язку зі складністю підготовки повного реєстраційного досьє в законодавстві багатьох країн, в тому числі країн Євросоюзу передбачено низку можливостей для спрощеної реєстрації ветеринарних препаратів шляхом подачі скороченого переліку матеріалів реєстраційного досьє.
 Здійснено аналіз відповідного законодавства ЄС, зокрема положень Директиви 2001/82 щодо спрощеної реєстрації ветеринарних препаратів. Визначено, що в праві ЄС передбачено можливість подачі неповного досьє у випадках реєстрації генеричних чи гібридних ветеринарних препаратів, ветеринарних препаратів з добре вивченим ветеринарним застосуванням, ветеринарних препаратів з фіксованою комбінацією, ветеринарних препаратів, що реєструються за інформованою згодою. Доведено, що на сьогодні правове регулювання такої реєстрації в Україні потребує вдосконалення.

Administrative guidance on submission of dossiers and assessment reports for the peer‐review of pesticide active substances

This document provides guidance to applicants submitting dossiers for approval of pesticide active substances, and to Member States preparing assessment reports on active substances within the scope of Regulation (EC) No 1107/2009 and Commission Implementing Regulation (EU) No 844/2012 and its subsequent amendments. It describes the administrative requirements for the preparation and submission of the dossier to support an application for the approval, the amendment of approval or the renewal of an existing approval of a pesticide active substance. The procedure and the associated timelines for handling applications for approval, from their submission to the adoption and publication of the EFSA conclusion are also described. This document also provides additional guidance with the aim to enhance the quality of dossiers and assessment reports. It provides instructions, guidance and templates for both the applicant and Rapporteur Member State on how data should be presented in the dossier and in the assessment report. The document finally presents the different possibilities applicants have to interact with EFSA staff under this peer review process and the support initiatives available during the different stages of the application life-cycle.

An Overview of the Drug Registration Requirements for Export to Tanzania, Nepal, and Cambodia

In the semiregulated market, different countries have varying requirements of registration for export to such a specific country or region. The objective of the present study is to give a comparative overview of pharmaceutical registration requirements for export to Tanzania, Nepal, and Cambodia. In the African region especially, east Africa including Tanzania is an emerging market for pharmaceuticals. The Tanzania Food and Drugs Authority is the drug regulatory body in Tanzania and it follows the Common Technical Document (CTD) format for dossier submission. However, Nepal is still a developing country with respect to the pharmaceutical sector. The drug governing body in Nepal, Department of Drug Administration, has its own nation-specific guidelines for drug regulation, but the CTD format is also acceptable for dossier submission. In Cambodia, the Department of Drugs and Food is the drug regulatory authority that comes under the Ministry of Health of Cambodia. As Cambodia is included in the Association of Southeast Asian Nations (ASEAN) body, it follows the ASEAN CTD (ACTD) format for dossier submission.

Registration Requirement and Approval Procedure of Vaccines in Saudi Arabia

Vaccination is one among the foremost cost-efficient health interventions out available, saving a lot of individuals from illness, incapacity, and death annually. So that it is very much essential for the people on time vaccination. Due to the variation of regulatory requirements and process in developing and emerging countries leads to set back vaccine's registration and therefore marketing a high-quality, safe and efficacious vaccines are delayed for their respective populations. This article focuses on providing clear registration requirements and approval procedure for vaccines in Saudi Arabia for marketing authorisation applications for vaccines and also tells the clear pathway for submission and approval of dossier for Saudi Arabia. The Module 1 of the Common Technical Document (CTD) and Modules 2–5 of the CTDs requirements are same as ICH CTD (Exceptions for some of the tests that we do not carry out for vaccines). A dossier containing detailed information about the vaccines and results of the studies carried out in its development process. Characterise the registration requirement and current regulatory review process used at SFDA, identifying agency review models as well as key milestones and timelines.

Information required for dossiers to support demands for import of high risk plants, plant products and other objects as foreseen in Article 42 of Regulation (EU) 2016/2031

Article 42 of the new Plant Health Law (Regulation (EU) 2016/2031 on protective measures against pests of plants), introduce a concept of “high risk plants, plant products and other objects” in relation to the presence of a pest risk of an unacceptable level for the Union territory, identified on the basis of a preliminary assessment to be followed by a risk assessment. Upon request of the European Commission (EC), the European Food Safety Authority (EFSA) defined the information required and developed a format for the preparation and submission of technical dossiers from third countries to support demands for import of high risk plants, plant products and other objects as foreseen in Article 42(5) of Regulation (EU) 2016/2031. The draft of this Technical Report was circulated to the EFSA Scientific Network for Risk Assessment in Plant health for commenting. The aim of this Technical Report is to enable the applicants to provide in their technical dossiers the information needed by EFSA to perform a Commodity Risk Assessment. The information required concerns: 1) the commodity (characterization of product and the description of the production process); 2) the pests potentially associated with the commodity in the exporting country; 3) the data on phytosanitary mitigation measures and inspections. Instructions on how this information should be presented are also provided.

Regulatory requirements for the registration of generic medicines and format of drug dossiers: procedures in Sri Lanka in comparison with selected regulatory authorities

BackgroundThe regulatory requirements for approval of generic medicines and the format of compiling drug dossiers vary among regulatory authorities. The variation is particularly wide between High-income countries (HIC) and lower and middle-income countries (LMIC) with different regulatory frameworks. In this study, document requirements for approval of generic products, approval timelines, and consideration of bioequivalence and/or biowaiver data by Regulatory Authorities (RAs) of 10 selected jurisdictions was studied.MethodsThe guidelines and procedures from 5 purposively chosen RA of HIC and4 regional RAs relevant for Sri Lanka were compared with the Sri Lankan National Medicines Regulatory Authority (NMRA). Information available in the official websites of the selected RAs, published journal articles and via personal communication was collected in2016. Drug approval timelines achieved in Sri Lanka was obtained from data available from another study.ResultsCommon technical dossier (CTD) format of the International Council on Harmonization (ICH) for registration of pharmaceuticals (ICH:CTD) or the Association of South East Asian Nations (ASEAN) CTD format (ACTD) was used by all RAs studied except Sri Lanka which use its own dossier format. Nine out of ten RAs studied request BE data or justification for not submitting BE data for generic medicines. Sri Lanka requested BE studies only for antimicrobials, antiepileptic drugs and narrow therapeutic index drugs. Biowaivers are allowed for Biopharmaceutics Classification System (BCS)-based Class 1drugs in Singapore and India. USA, EMA, Canada and South Korea allowed biowaiver for BCS Class1and Class 3drugs but Sri Lanka does not accept BW at present. Nine NMRAs out of the ten studied reported legislated timelines for approval of generic pharmaceuticals except Sri Lanka.ConclusionsStreamlining the drug regulatory systems in LMIC such as Sri Lanka with that of HIC would facilitate an effective drug regulatory system based on reliance on decisions made by stringent regulatory authorities. Findings of this study encourage Sri Lanka to adopt a CTD format for regulatory submission of drug dossiers. Expanding the BE requirement drug list and accepting BCS-based biowaivers for BSC class 1 and 3 drugs during registration of generic drugs when it is scientifically justified is also recommended for Sri Lanka.

Regulatory requirements for Dossier submission in African Countries (Kenya, Uganda, and Tanzania) - A Review

Africa is world’s second fastest growing pharmaceutical market. The CGAR of African Pharmaceutical market is 10.6%. African people suffer from numerous diseases. The local pharmaceutical market is weak and insufficient to meet the demand of such diseased condition and so Africa relies heavily on externally developed and procured drugs. This combination of economic strength and prevalence of diseases is already driving a demand for medicines across Africa. The objective of this study is to delve in various parameters required for registration for externally developed pharmaceutical product African countries. A dossier containing detailed information about the drug and results of the studies carried out in its development process has to be submitted to the regulating bodies for getting market authorization. CTD is critical for dossier submissions. A comparative study will help the sponsor to file the dossier in many countries simultaneously; which can save time and money. Thus knowledge of guideline specific for individual country becomes important to determine the most stringent member, which shall ease approval process in other target countries in the region.

HT1 - Similarities and Differences in European HTA Evidence Requirements: One for All or One for None?

To determine similarities in requirements and timeline alignment in health technology assessment (HTA) submissions across Europe. Current country differences challenge harmonization and parallel scientific advice with regulatory bodies. Submission guidance from HTA bodies in the UK (England and Wales; Scotland), France, Germany, The Netherlands, Belgium, Denmark, Finland, Norway, Sweden, Poland and Portugal were reviewed. Evidence requirements (e.g., therapeutic benefit, patient benefit, economic evaluations) and timelines for submissions were identified and compared. Requirements of assessment of therapeutic benefit, patient benefit, systematic literature reviews and dossier submissions were consistent across countries. Economic assessment criteria vary across countries. The UK, France, Norway, and Germany recommend a payer perspective and others recommend some form of a societal perspective (Poland, Denmark, Finland, Sweden, and the Netherlands). Differences in preferences for economic perspective drive further differences in economic analyses recommended by HTA bodies. Most HTA bodies suggest cost-utility analysis (CUA) but some a cost-effectiveness analysis (CEA), adding complexity to the development of global economic models and country adaptations. All countries recommend a budget impact model and the Nordics propose a cost calculation. In terms of health-related quality of life evaluation, all countries recommend both generic and disease-specific measures. There is a high degree of variability in mean time from submission to reimbursement across countries. Most countries report an expected mean of 180 days from submission to reimbursement; however, in practice this can extend in some countries to approximately one year (360-400 days). Exceptions include the Netherlands and Denmark, which report an expected 90 days from submission to reimbursement and Germany is the outlier with 12-month free pricing from the time of submission. Despite several similar requirements for HTA submissions to multiple countries, harmonization is challenged by differences in both economic evaluations and submission to reimbursement timelines.

Quality Issues Identified During the Evaluation of Biosimilars by the European Medicines Agency's Committee for Medicinal Products for Human Use.

The aim of this study was to identify trends in deficiencies raised during the EU evaluation of the quality part of dossiers for marketing authorisation applications of biosimilar medicinal products. All adopted day 120 list of questions on the quality module of 22 marketing authorisation applications for biosimilars submitted to the European Medicines Agency and concluded by the end of October 2015 was analysed. Frequencies of common deficiencies identified were calculated and summarised descriptions included. Frequencies and trends on quality deficiencies were recorded and presented for 22 biosimilar applications. Thirty-two 'major objections' for 9 products were identified from 14 marketing authorisation applications with 15 raised for drug substance and 17 for drug product. In addition, 547 'other concerns' for drug substance and 495 for drug product were also adopted. The frequencies and trends of the identified deficiencies together with their impact were discussed from a regulatory perspective and how these impact key manufacturing processes and key materials used in the production of biosimilars. This study provides an insight to the regulatory challenges prospective companies need to consider when developing biosimilars; it also helps elucidate common pitfalls in the development and production of biosimilars and in the submission of dossiers for their marketing authorisations. The results are expected to be of interest to pharmaceutical companies but also to regulators to obtain consistent information on medicinal products based on transparent rules safeguarding the necessary pharmaceutical quality of medicinal products.