An Evaluation of the Swissmedic Regulatory Framework for New Active Substances.

Background: Swissmedic is a major regulatory agency that has been benchmarking its timelines for 20 years. To better understand the Swissmedic review times and to examine whether measures introduced to accelerate the process were effective, a retrospective analysis was undertaken. The objective was to provide a breakdown of where time is spent in the phases of Swissmedic's approval process (validation, scientific assessment, authorisation) and how this compared to other major authorities.

Evaluation of Risk-Based Approaches to the Registration of Medicines: Current Status Among African Regulatory Authorities.

Background: Despite the worldwide need for increased access to safe and effective medicines, there is a lack of innovative medicines in many low- to middle-income countries. On the African continent, this is partly due to capacity limitations of National Regulatory Authorities (NRAs). One important approach to address this issue is work sharing and regulatory reliance.

Regulatory, health technology assessment and company interactions: the current landscape and future ecosystem for drug development, review and reimbursement.

Background: Multi-stakeholder interactions have evolved at product and policy levels. There is a need to assess the current and future landscape of interactions between companies, and regulatory and HTA agencies to address challenges and identify areas for improvement.

Objectives: The aims of this study were to review the current interactions within and across regulatory and HTA agencies, and companies' experiences in engaging in these activities; to assess the added value of interactions as well as limitations; to explore the future ecosystem for stakeholder interactions.

Challenges and Opportunities for Companies to Build HTA/Payer Perspectives Into Drug Development Through the Use of a Dynamic Target Product Profile.

The target product profile (TPP) outlines the desired profile of a target product aimed at a particular disease and is used by companies to plan clinical development. Considering the increasing importance of health technology assessment (HTA) in informing reimbursement decisions, a robust TPP needs to be built to address HTA needs, to guide an integrated evidence generation plan that will support HTA submissions. This study assessed current practices and experiences of companies in building HTA considerations into TPP development.

Evaluation of the Performance of the Gulf Cooperation Council Centralised Regulatory Review Process: Strategies to Improve Product Authorisation Efficiency and Quality.

Background: The Gulf Centralised Committee for Drug Registration (GCC-DR), as part of the Gulf Health Council (GHC), enables the consolidated registration of pharmaceutical products throughout the member states of the Gulf Cooperation Council.

Objectives: The objectives of this study were to provide an update of the performance of the GCC-DR centralised procedure; evaluate the review times for new products submitted to the GCC Centralised Registration between January 2015 and December 2020; assess the impact of applying facilitated regulatory pathways and implementing a reliance strategy; identify the strengths and weaknesses of the centralised review process; and propose strategies that could enhance the GCC regulatory review process leading to improved access to medicines for patients.

Methods: A standardised data collection template enabled the structured documentation of information collected by the Senior Regulatory Affairs and Regulatory Affairs Specialists from the Executive Board of the Health Ministers Council for GCC States to determine the GHC structure, resources, review models and milestones and timelines.

Building HTA insights into the drug development plan: Current approaches to seeking early scientific advice from HTA agencies.

There is a growing trend for pharmaceutical companies to seek scientific advice on drug development from a Health Technology Assessment (HTA) perspective, to improve the efficiency of their studies, enable better trial design, and support the goals of positive HTA recommendation for reimbursement. This study uses information collected directly from companies on individual products to assess their strategies and practices for seeking HTA-related scientific advice in terms of which stakeholders to engage and for what purpose, when to seek scientific advice, and whether to implement that advice within global clinical development.

Transparency in European Medicines Agency and US Food and Drug Administration Decision Making: Is It Possible to Identify the Rationale for Divergences in Approved Indication From Public Assessment Reports?

Although it cannot be expected that different medicines' regulatory agencies always reach the same review outcome, it is important that decision making is documented and communicated to ensure transparency. This study examines whether justification for divergences between the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) regarding approved indications could be identified from the agencies' public assessment reports (PARs). We focused on 9 products previously identified to have been submitted simultaneously to both agencies with the same indication but had a different indication approved; there were 15 differences in indications.

The Qualitative Value of Facilitated Regulatory Pathways in Europe, USA, and Japan: Benefits, Barriers to Utilization, and Suggested Solutions.

Background: Despite the growing application of facilitated regulatory pathways (FRPs), little attention has focused on assessing the perception of pharmaceutical companies regarding their usefulness beyond increasing timeliness.

Objectives: The aim of this study was to characterize the perceived value of four key FRPs, based on industry experiences in using these pathways. In addition, we sought to characterize the perceived impact based on benefits and barriers as well as suggested solutions for their use and recommendations as identified by companies, to outline how these FRPs may be further evolved as tools for expediting the development and regulatory review of important medicines.

Companies' Health Technology Assessment Strategies and Practices in Australia, Canada, England, France, Germany, Italy and Spain: An Industry Metrics Study.

Health technology assessment (HTA) has increased in importance in supporting payer decision making by assessing the relative effectiveness and cost effectiveness of new medicines. Thus, pharmaceutical companies need to address the HTA requirements early during development to improve reimbursement outcomes. Currently, there is a lack of research to assess the impact of HTA on development and jurisdictional outcome from companies' perspectives.

An evaluation of the Caribbean regulatory system centralized assessment process for medicines submitted 2017-2018 using the OpERA methodology.

Background: The Caribbean Regulatory System is a centralized medicine assessment procedure established to serve the needs of the Member States of the CARICOM region. In order to better understand the effectiveness and efficiency of the processes implemented by the Caribbean Regulatory System for the regulatory assessment of medicines for the region, the system has been participating in the Optimizing Efficiencies in Regulatory Agencies (OpERA) program, a multinational endeavor to characterize the assessment procedures and the corollary metrics associated with medicine review activities in regulatory agencies and regional regulatory initiatives.

Methods: The OpERA tool was used to collect process and specific milestone data for products approved by the Caribbean Regulatory System during 2017 ( = 10) and 2018 ( = 11).

Benchmarking health technology assessment agencies-methodological challenges and recommendations.

Objectives: The objectives of the study were to establish a benchmarking tool to collect metrics to enable increased clarity regarding the differences and similarities across health technology assessment (HTA) agencies, to assess performance within and across HTA agencies, identify areas in the HTA processes in which time is spent and to enable ongoing performance improvement.

Methods: Common steps and milestones in the HTA process were identified for meaningful benchmarking among agencies. A benchmarking tool consisting of eighty-six questions providing information on HTA agency organizational aspects and information on individual new medicine review timelines and outcomes was developed with the input of HTA agencies and validated in a pilot study.

Correction to: An Evaluation of Malaysian Regulatory Process for New Active Substances Approved in 2017 Using the OpERA Methodology.

The authors have revised Figure 1. The revised figure is presented below.

An Evaluation of Malaysian Regulatory Process for New Active Substances Approved in 2017 Using the OpERA Methodology.

Introduction: The National Pharmaceutical Regulatory Agency (NPRA) embarked on a regulatory-strengthening program and is evaluating its processes. Optimising Efficiencies in Regulatory Agencies (OpERA) is a regulatory-strengthening program that provides benchmarking data that can define performance targets and focus performance improvement. The objective of this study was to use OpERA methodology to determine where time is spent in the NPRA approval process and to form a baseline to measure the performance improvements.

Implementation of a Framework for an Abridged Review Using Good Reliance Practices: Optimising the Medicine Regulatory Review Process in South Africa.

Background: This study sought to identify criteria and current practices for implementing an abridged review process and understanding barriers and enablers in utilizing reliance models and to offer recommendations for the implementation of an abridged review process in South Africa based on good reliance practices (GRelP).

Methods: A questionnaire was completed by six national regulatory authorities (NRAs) to determine criteria and current practices for implementing an abridged review process. In addition, two focus group discussions were conducted on the practical implementation of an abridged review process based on GRelP.

Use of the Certificate for Pharmaceutical Products (CPP) in 18 Maturing Pharmaceutical Markets: Comparing Agency Guidelines with Company Practice.

Background: The certificate of pharmaceutical product (CPP) was implemented to accelerate the availability of new drugs in developing countries by providing evidence of the quality of products and reducing the time to market through reliance on a prior trusted analysis. However, the CPP format, issuing process and use have not been revised since 1997 and there are significant differences among countries in regard to requirements for CPP timing, terminology, and format. We sought to determine current CPP practices versus national regulatory guidelines and to inform recommendations for the efficient use of the CPP based on the needs of the modern regulatory environment.

A Process for Evaluating Quality Decision-Making Practices During the Development, Review and Reimbursement of Medicines.

Background: The development of a medicine is not only underpinned by good science but also by Quality DecisionMaking Practices (QDMPs). Indeed, it is important to ensure that all organisations involved in the lifecycle of medicines are aligning their practices in decision-making to the QDMPs to ensure quality, transparent and consistent decisionmaking processes.

Methods: The aim of this study was to evaluate the practicality of QoDoS (Quality of Decision-Making Orientation Scheme) in assessing the incorporation of ten QDMPs during the development, review and reimbursement of medicines, illustrated by case studies with a pharmaceutical company, a regulatory authority and a health technology assessment (HTA) agency.

A Baseline Analysis of Regulatory Review Timelines for ANVISA: 2013-2016.

Background: The Brazilian health regulatory agency (Agência Nacional de Vigilância Sanitária, ANVISA) has embarked on transformational initiatives to fulfill its mandate to provide timely access to safe, effective, and quality therapeutics. A new Brazilian law was enacted to provide the agency with greater flexibility. Optimizing Efficiencies in Regulatory Agencies (OpERA) is a regulatory-strengthening program that seeks to provide benchmarking data that can be used to define performance targets and focus performance improvement.

Quality Decision-Making Practices in Pharmaceutical Companies and Regulatory Authorities: Current and Proposed Approaches to Its Documentation.

Background: Pharmaceutical companies and regulatory agencies endeavor to relate their decision making with outcomes to improve future decision making and to ensure that gained knowledge is fed back into a learning system. Nevertheless, such a correlation can only be achieved by documenting the expected outcome of a decision at the time it is made, enabling comparison of the expected outcome with the actual result.

Methods: Participants at an international workshop discussed how the documentation of decisions could be evolved as companies and agencies look to improve their knowledge base.

Quality Decision Making in Health Technology Assessment: Issues Facing Companies and Agencies.

Background: To evaluate the quality of the decision-making processes of pharmaceutical companies during medicines development for evidence generation to support reimbursement of new medicines and the appraisal recommendation decision-making process by health technology assessment (HTA) agencies.

Methods: Two questionnaires were developed and subsequently piloted for the purpose of content validation. These were sent to 24 pharmaceutical companies and 16 HTA agencies.

A Proposed Framework for a Globally Applicable Pragmatic Approach to Using Facilitated Regulatory Pathways.

Background: As regulatory agencies come under increased pressure to review medicines of critical importance through efficient regulatory systems to provide equitable access, the benefits of using expedited review pathways are being explored. These facilitated regulatory pathways (FRPs) provide a variety of review strategies that can also expedite assessments. Stringent regulatory authorities (SRAs) use primary FRPs to accelerate development or to shorten review time.

To what degree are review outcomes aligned for new active substances (NASs) between the European Medicines Agency and the US Food and Drug Administration? A comparison based on publicly available information for NASs initially approved in the time period 2014 to 2016.

Objective: To compare review outcome alignment between European Medicines Agency (EMA) and US Food and Drug Administration (FDA) for medicines approved by both agencies in the time period 2014-2016.

Design: Using publicly available information from FDA and EMA websites, new active substances (NASs) approved by each agency from 2014 to 2016 were identified and their characteristics assessed. Divergences in regulatory outcomes for simultaneous (within 91 days) submissions to both agencies were identified and then examined for use of facilitated regulatory pathways and orphan designations; submitted versus approved indications; and approval times.

The Reliability and Relevance of a Quality of Decision Making Instrument, Quality of Decision-Making Orientation Scheme (QoDoS), for Use During the Lifecycle of Medicines.

The Quality of Decision-Making Orientation Scheme (QoDoS) was developed to provide organisations involved in submission, approval and reimbursement of new medicines with a tool to improve the quality of their decision-making processes and is considered the most promising tool for such purpose. This study aimed to further establish the measurement properties of the QoDoS by evaluating its reliability (internal consistency and test-retest reliability) and relevance in the target population. The study participants consisted of 55 individuals recruited from pharmaceutical companies, regulatory and HTA agencies.

The Confluence of Accelerated Regulatory and Health Technology Assessment Access Pathways.

There is a growing interest in aligning accelerated regulatory pathways with flexible access and reimbursement pathways to expedite the equitable availability of high-quality, safe, and effective medicines that provide a value-based approach to meeting society's most important healthcare needs. The Centre for Innovation in Regulatory Science (CIRS) identified key issues regarding the confluence of regulatory and health technology assessment processes from discussions and presentations given by international regulators, health technology assessment bodies, payers, patient representatives, and multinational pharmaceutical company representatives on this topic at CIRS workshops held in 2014 and 2017 that focused on the commonalties and differences across these pathways. Recent publications have also been highlighted.

The Benefit-Risk Assessment of Medicines: Experience of a Consortium of Medium-Sized Regulatory Authorities.

Background: In 2008, a consortium of 4 regulatory authorities, the Australian Therapeutic Goods Administration (TGA), Health Canada, Swissmedic, and Singapore Health Sciences Authority (HSA) approached the Centre for Innovation in Regulatory Science (CIRS) to support the development of a benefit-risk framework and template that could be used by all 4 authorities and that would enable joint and shared reviews to maximize resources. CIRS facilitated this collaboration, the Consortium on Benefit-Risk Assessment (COBRA), between 2008 and 2013.

Methods: COBRA developed a benefit-risk assessment template based on the EMA reflection paper of 2008, which was constructed and then evaluated in 3 phases: a feasibility study, a retrospective pilot study, and a prospective study.

Building Synergy between Regulatory and HTA Agencies beyond Processes and Procedures-Can We Effectively Align the Evidentiary Requirements? A Survey of Stakeholder Perceptions.

Objectives: To evaluate the current practice of companies and agencies to assess the changes made in aligning regulatory and health technology assessment (HTA) stakeholders; to identify areas of commonality of evidentiary requirements that could occur; and to identify strategic issues and trends of regulatory and HTA synergy.

Methods: Two separate questionnaires were developed to assess stakeholders' perceptions on regulatory and HTA alignment, one for pharmaceutical companies and the other for regulatory and HTA agencies. The responses were analyzed using descriptive statistics.