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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., Methods: Data on Swissmedic, EMA and FDA product approvals were collected from websites or through direct communication, using a standardised CIRS method and milestones previously identified, focusing on new active substances approved 2019-2021., Results: In 2019, 2020, and 2021, Swissmedic median approval times were 520, 470, and 392 days, respectively. The decrease over this time was mainly observed in the Authorisation Phase and can be attributed to lower proportions of applications with multiple "labelling loops", in addition to shorter times for final label negotiation. While Swissmedic had the longest overall approval time (447 days) compared to EMA (428) and FDA (244), the timelines were more comparable when considering only the agency's time spent on the scientific assessment, with Swissmedic at 194 days, EMA at 218 days, and FDA at 184 days., Conclusions: These observations represent an important analysis of Swissmedic regulatory activity timelines, demonstrate the impact of process improvements, and emphasise the importance of measuring timelines. Swissmedic will continue to expedite its processes also by promoting international collaborations with like-minded authorities., (© 2023. The Author(s).)

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., Methods: We conducted a comparative analysis of company practice versus agency guidelines across 18 maturing pharmaceutical markets using data from the Cortellis for Regulatory Intelligence® (CRI) and the Centre for Innovation in Regulatory Science (CIRS) Emerging Markets Regulatory Review Times (EMaRReT) databases and regulatory authorities' websites., Results: Of the studied 18 countries, 16 require the CPP for submission of new registrations; many accept alternative documentation but most still require legalization of the CPP and many are not compliant with the complex CPP format. Additional complicating factors include language requirements and varying local guidelines for CPP submission timing and validity dates., Conclusions: With the implementation of a number of suggested improvements, the CPP can continue to serve an important role in streamlining regulatory efficiency and provide confidence in new medicines, ensuring a more efficient and effective approval process and expediting patient access to safe and effective medicines worldwide.

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. The objective of this study was to use OpERA methodology to undertake a retrospective analysis of the timelines associated with important components of the ANVISA regulatory review process to establish a baseline against which the influence of the new law could be measured., Methods: The OpERA tool was used to collect specific milestone data that identify time periods, review stages, and data points for products approved by ANVISA 2013-2016., Results: For the 138 products approved in this cohort, the overall median approval time was 795 days. ANVISA and submitting companies will need to reduce their review and response times by approximately half in order to meet the total time goal of 365 days., Conclusions: The observations from this baseline study have identified opportunities for ANVISA and sponsor companies to collaborate to reduce regulatory assessment times while assuring the timely approval of safe and effective, quality medicines. These analyses will be repeated to determine how the provisions of the new Law will impact the activities of ANVISA and the extent of sponsors' contributions to this effort.

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. Discussions were informed by a pre-workshop survey of pharmaceutical companies and regulatory agencies., Results: Most survey participants from 12 companies (55% response rate) and 11 agencies (73% response) have a system in place to enable documentation of major decisions, however, systems are used primarily to document outcomes rather than the process, while information from documentation is not always used, and feedback loops are not in place. The majority of participants indicated that their organization currently documents most decision-making practices included in the proposed template. Workshop participants agreed that all major past decisions should be referenceable and suggested incentives to enable decisions to be referenced, and confirmed elements and characteristics of a decision-documentation template., Conclusions: This survey and workshop identified the current landscape and gaps in the documentation of decision making and suggested revisions for a proposed documentation template. The use of technology to enable information extraction with support from artificial intelligence and future decision making was a recommendation highlighted by participants.

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., Results: Participating NRAs indicated that reliance would be placed on one reference agency. Applications submitted to NRAs for an abridged review had to be identical to those submitted to the reference agency. Unredacted reference agency assessment reports would be required to facilitate the abridged review process. A full technical dossier would also be required, but only parts would be assessed during the abridged review. Focus groups indicated that abridged review elements had been identified and should be considered in implementing GRelP., Conclusions: NRAs strive to improve regulatory performance and accelerate approval times; however, many continue to face challenges due to resource constraints. Increasing workloads, advancing technologies, and limited expertise require NRAs to leverage regulatory convergence initiatives, collaborative registration procedures, and functional regional, continental and international networks to fulfil regulatory mandates. Recommendations for the implementation of an abridged review process and a framework for GRelP have been made with a view to optimise regulatory review processes in South Africa.

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., Methods: The OpERA tool was used to collect specific milestone data that identify time periods, review stages, and data points for new active substances and biosimilars approved by NPRA in 2017., Results: In 2017, 25 new active substances and 1 biosimilar were approved by NPRA in a median of 515 days, representing both agency and applicant time. The median time between dossier receipt and the initiation of NPRA scientific assessment was 135 days, but there was a wide variation in queuing time. The median total assessment time was 279 days (agency and applicant timing). NPRA took a median of 166 days; applicants took a median of 131 days to respond to deficiency questions, with up to 6 cycles of review required for approval and 65% of applications requiring 4-5 cycles to provide satisfactory responses., Conclusions: As a result of these data, NPRA proposes three improvements: target start for scientific assessment 100 days after file acceptance, a maximum of 5 review cycles, and applicant response time limited to 6 months. These results will serve as a baseline for further assessment.

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., Results: Responses were obtained from 11 companies and 11 HTA agencies. Some similarities were identified between the decision-making processes of companies and agencies, such as the use of committees, having a primarily mixed (qualitative/quantitative) internal decisionmaking system, as well as the lack of systematic assessments of quality decision making and the relatively infrequent use of formal decision-making frameworks. Nevertheless, the results indicate differences as companies and agencies use diverse processes to arrive at the final decision either through consensus, majority vote, or an individual making the decision. The majority of companies and agencies believe that the quality of decision making can and should be measured. Moreover, organizations considered the occurrence of biases within their organization as pertinent. Finally, almost all the participants felt that there was room for improvement for their organization's quality of decision making., Conclusion: These findings are consistent with a published study on regulatory processes and support the need for more consistent and predictable decision-making processes during the life cycle of medicines. This could be achieved through capacity building, systematically evaluating the quality of decision making, and encouraging utilization of formal decision-making frameworks within companies and agencies.

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. Some emerging national regulatory authorities can implement primary FRPs but are more likely to use secondary FRPs that rely on or recognize an SRA or reference agency decision, the World Health Organization Collaborative Prequalification of Medicines Programme, "altruistic" reviews, or collaborative work sharing. Despite their availability, there are no formal guidelines or consensus for the definition, basic elements, or best practices for FRPs., Methods: Herein, we present a 4-step pragmatic approach to a framework designed to help agencies determine how best to use FRPs. Each step is based on characteristics identified through research, surveys, literature assessments, regulatory capacity categorization analyses, and practical experience., Results: Step 1 assesses 4 domains of the environment preparedness, step 2 offers process criteria that should be in place to effectively use an FRP, step 3 tiers agencies through a self-assessment of readiness and capacity, and step 4 provides a pathway for agencies to determine the most relevant FRP for their use. Target timelines are proposed for FRPs., Conclusions: This framework represents the first endeavor to holistically address the multifaceted aspects that should be considered for the effective use of an FRP.

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. The final template corresponded to the Universal Methodology for Benefit-Risk Assessment (UMBRA) developed by CIRS., Results: By 2014, elements of the template, which had been developed during the program of work, aided the authorities in documenting the benefit-risk assessment of medicines in a systematic and structured way. However, its role in the individual authority's assessment toolkit was influenced by the number of key elements within the template that were already included in their current clinical assessment templates. Notably, the agencies indicated that they will modify their clinical assessment templates to align with the UMBRA 8-step framework approach., Conclusions: Overall, the authorities believed that the project had given them a better understanding of the value of using a structured approach to the benefit-risk assessment of medicines as well as enabling shared learnings between the authorities.

Background: Although the quality of decision making (QDM) in the development and regulatory review of medicines influences the delivery of new products, there appears to be no suitable instrument to assess QDM in this area. The aim of this study was to assess differences in QDM using a validated instrument, the Quality of Decision-Making Orientation Scheme (QoDoS), to identify best practices and biases affecting individuals and their organization, as well as to assess differences in decision-making behaviors between pharmaceutical companies and regulatory agencies. QoDoS also enables the measurement against 10 quality decision-making practices (QDMPs) that underpin a quality process., Methods: QoDoS, consisting of 47 items that assess individual and organizational decision-making approaches and influences, was completed by 76 participants from regulatory agencies and pharmaceutical companies., Results: Having a systematic, structured approach to aid in decision making is achieved to a greater extent at an individual level (72%) compared with that of the organization (38%). Key differences between company and agency decision making were uncovered. While it was recognized that both stakeholders felt that their decision making could be improved (100% agencies; 92% companies), training in the science of decision making was rarely provided., Conclusions: QoDoS has the ability to measure differences in QDM between individuals and organizations within companies and agencies. The benefits of assessing QDMPs with QoDoS include enabling an increased awareness of biases and best practices that should be incorporated into a decision-making framework; increasing productivity and reducing uncertainty around decision making, thereby resulting in more predictable outcomes for organizations. In addition, it provides a basis for discussion of the issues in decision making within an organization as well as between stakeholders to encourage a level of partnership. Finally, measurements of QDM will enable trust, consistency, transparency, and timeliness to be built into critical decisions that affect medicines' availability.

Background: This study compared the timing, regulatory marketing authorization decisions, and the final labeling for products submitted to Swissmedic to those submitted to European Medicines Agency (EMA) and the US Food & Drug Administration (FDA)., Methods: The Centre for Innovation in Regulatory Science (CIRS) conducted an analysis of a representative cohort of 63 new molecular entities (NMEs) that were submitted to Swissmedic from 2006 through 2010 and that were also submitted to, and approved by, the EMA centralized procedure and FDA. Parameters considered included the outcome and timing of regulatory marketing authorization decisions and the comparison of each product's Summary of Product Characteristics (SPC) from the 3 agencies. The results were presented at the Swissmedic 10th Anniversary Symposium, "The Challenges of Regulation and Changing Regulations Paradigms," and they form the basis of this article., Results: The median approval times for these NMEs were longer for Swissmedic (480 days) compared with FDA (303 days) and EMA (416 days). However, if an expedited application review procedure (a "priority review" [FDA], "accelerated assessment" [EMA], or "accelerated review" [Swissmedic]) was applied, Swissmedic was faster (207 days) than EMA (300 days) and essentially as fast as FDA (229 days). The main differences were in the nature of the wording of parts of the initial SPC, particularly the "Contraindications" and "Special warnings and precautions" for FDA and "Special warnings and precautions" for EMA., Conclusions: Results suggest there is no clear evidence that Swissmedic was substantially different in its initial regulatory decisions or SPC recommendations compared with the EMA or FDA.

Background: The science of decision making is well established, although in reality it is a mixture of science and art. What is currently lacking is research into decision making in medicines research and development. The aims of this study were to determine the current decision-making practices and methodologies for measuring the quality of the decision making and the barriers and solutions for making quality decisions within pharmaceutical companies and regulatory agencies., Methods: Two analogous questionnaires were developed for use in this study. Fourteen agencies and 25 companies were asked to complete the questionnaire, assessing their decision making for submitting or approving a new drug application., Results: The 68% and 71% response rate from companies and agencies, respectively, suggests interest in this topic, but the area is largely unexplored within the pharmaceutical environment. Moreover, all companies and 90% of the agencies believed that decision making at their organizations could be improved. Although both stakeholders have, to some extent, already implemented frameworks and various methodologies, these are often informal and unsystematic. Challenges remain and there is a need to change the organizational culture by increasing the awareness of the quality aspect in decision making., Conclusions: The findings of this study support the need to further characterize and assess the practices and behaviors of individuals and organizations. Furthermore, the barriers, mainly relating to the influence of biases, should be addressed by developing the general principles of a formal quality decision framework and identifying quality decision-making practices in order to ensure that structured decisions are made throughout the life cycle of medicines.

A universal framework for the evaluation of the benefit-risk assessment of medicines during development by pharmaceutical companies and in the regulatory review by regulatory authorities is considered of value, as it would result in the systematic structured approach to support transparency in decision making. Several organizations have developed frameworks over the past few years, including those recommended by pharmaceutical companies such as the PhRMA BRAT (Pharmaceutical Research and Manufacturers of America Benefit-Risk Action Team) and the BRAIN (Benefit-Risk Assessment in New and Old Drugs) as well as frameworks advanced by regulatory agencies, including the FDA 5-step framework and the EMA PrOACT-URL. However, a review of the criteria-including logical soundness, comprehensiveness, acceptability of results, practicality, specificity and sensitivity, presentation (visualization), and scope proposed for the development of a universal framework-demonstrated that all these different frameworks described can be incorporated into UMBRA (Universal Methodology for Benefit-Risk Assessment).

As a first step in the implementation of the Asia-Pacific Economic Cooperation (APEC) Best Regulatory Practice Project, the Centre for Innovation in Regulatory Science conducted a gap analysis survey among regulatory agencies of 14 APEC member economies to assess the current use of good review practices (GRevP) to support transparent, consistent, predictable, and good-quality regulatory decision making. Although the majority of responding agencies have established some form of GRevP, most practices are currently evolving and are applied on an informal basis. Most agencies have developed standard operating procedures and guidelines and use a variety of training methods. The use of a common approach to regulatory review across jurisdictions would help build trust and confidence in each agency's processes, setting the stage for the possibility of work sharing across resource-constrained agencies and bringing consistency and transparency to the review process.