Funding and financial sustainability of pharmacovigilance: suggested models for funding pharmacovigilance in resource-limited African countries.

Background: An important factor hindering the growth of pharmacovigilance (PV) in resource-limited settings is the lack of adequate funds to establish a functional National Pharmacovigilance System. Consequently, the crucial function of monitoring and ensuring the availability of safe medicines in these settings cannot be guaranteed considering the peculiarities of diseases and medicines used. Objectives: The objective of this paper is to provide an overview as to the availability of potential sources of funds, which could be explored to ensure Medicine Safety and to proffer a potential framework likely to ensure sustainable funding of PV in Africa. Methods/processes: The process of developing this framework entailed a review of PV financing in some developed economies, a landscape study of funding of PV in some African countries, an in-depth understanding of the PV system and the organisational structure and nexus between the regulatory agencies and National Pharmacovigilance Centre. Critical points for consideration included the sources of funds, revenue pool, the disbursement of funds, budgeting and expenditure profile and the legal framework. Consultative meetings, webinars and interviews with experts were carried out. Results: The findings showed that most of the PV systems were mainly integrated into the regulatory agencies regarding operational and fiscal governance with few facilities being independent of the regulatory agencies. The main source of funding was from the government with significant donor funding which is ad hoc and non-sustainable. Several potential sources were identified but yet to be exploited. There were no legal provisions for PV financing. A framework likely to ensure sustainable PV financing is suggested to capture all available sources of funding, mine the potential sources providing a sizeable pool of revenue to address its activities and enabling legal framework which will engender autonomy. Furthermore, it will address the nexus between the regulatory agencies and the PV outfits, thus enabling appropriate share of resources and blockage of diversions. Conclusion: In all, addressing the various elements identified in this study and providing the legal provisions which guarantees some degree of autonomy will provide a sustainable mechanism for PV funding in the resource-limited setting of Africa.

Funding models for pharmacovigilance in resource-limited African countries An important factor hindering the growth of pharmacovigilance (PV) in resource-limited settings following their entry into the WHO Programme of International Drug Monitoring is the lack of adequate funds to establish a functional National Pharmacovigilance System. This article provides an overview of various potential sources of funds in these settings and how they can be harnessed to fund PV. We undertook a review of PV financing in developed settings and carried out a landscape study of funding of PV in some African countries, as well as having an in-depth understanding of the PV system and the organisational structure. The nexus between the regulatory agencies and National Pharmacovigilance Centre was noted. We took into account the sources of funds, revenue pool, the disbursement of funds, budgeting and expenditure profile and the legal framework for the different African countries. We also identified the prevalent and potential sources of funds for PV. Consultative meetings, webinars and interviews with experts in PV were carried out as well. We discovered that most of the PV facilities were mainly integrated into the regulatory agencies regarding operational and fiscal governance with few facilities being independent of the regulatory agencies. The main source of funding was from the government with significant donor funding which is ad hoc and non-sustainable. Several potential sources were identified but yet to be exploited. There were no legal provisions for PV financing. We have now proposed funding models that may lead to increased revenue for PV in these countries as well as suggesting that a legal framework be provided to guarantee sustainability and address the nexus between the regulatory agencies and the PV outfits to ensure an appropriate share of resources and blocking diversions.

Pharmaceutical Industry Evaluation of the Effectiveness and Efficiency of the ZaZiBoNa Collaborative Medicines Registration Initiative: The Way Forward.

Introduction: The common technical document (CTD) format harmonised the requirements for the registration of medicines, which had traditionally differed from country to country, making it possible for countries to collaborate and conduct joint reviews of applications. One such collaborative medicines registration initiative is the Southern African Development Community ZaZiBoNa, established in 2013. A recent study was carried out with the nine active member regulatory authorities of the ZaZiBoNa to determine their views on its operational effectiveness and efficiency. Having obtained the authorities' views, the aim of this study was to evaluate the effectiveness and efficiency of the current operating model of the ZaZiBoNa initiative including the challenges it faces as well as identifying opportunities for improvement from the applicants' perspective. Methods: Applicants who had submitted registration/marketing authorisation applications for assessment under the ZaZiBoNa initiative during 2017-2021 were recruited into the study. Data was collected in 2021 using the Process, Effectiveness and Efficiency rating questionnaire (PEER-IND) developed by the authors. The questionnaire was completed by a representative responsible for ZaZiBoNa submissions in each company. Results: The pharmaceutical industry was of the view that the ZaZiBoNa initiative has achieved shorter timelines for approval of medicines, resulting in increased availability of quality-assured medicines for patients in the SADC region. Harmonisation of registration requirements and joint reviews have reduced the workload for both the pharmaceutical industry and the regulatory authorities. Some of the challenges identified were the lack of a centralised submission and tracking system, and the lack of information for applicants on the process for submission of ZaZiBoNa dossiers/applications in the individual countries, including contact details of the focal person. The establishment of a regional unit hosted in one of the member countries to centrally receive and track ZaZiBoNa dossiers/applications was identified as the best strategy for moving forward in the interim with the long-term goal being the establishment of a regional medicines authority. Conclusion: There was consensus between the pharmaceutical industry and the regulatory authorities as to the way forward to improve the effectiveness and efficiency of the ZaZiBoNa initiative. Implementation of the recommendations identified in this study will lead to enhanced regulatory performance.

Regulatory Authority Evaluation of the Effectiveness and Efficiency of the ZaZiBoNa Collaborative Medicines Registration Initiative: The Way Forward.

Introduction: ZaZiBoNa, the work-sharing initiative in the Southern African Development Community (SADC) that has been in operation for 8 years has successfully assessed over 300 dossiers/applications, with an overall median time to recommendation of 12 months. All 16 SADC countries participate in the initiative as either active or non-active members. While the successes of ZaZiBoNa are evident, some challenges still exist. The aim of this study was to solicit the views of the participating authorities on the effectiveness and efficiency of the current operating model of the ZaZiBoNa initiative. Methods: Data were collected in 2021 using the Process, Effectiveness and Efficiency Rating (PEER) questionnaire developed by the authors. The questionnaire was completed by the focal person in each country and approved by the head of the authority. Results: ZaZiBoNa serves as a platform for work sharing, information exchange, capacity building and harmonisation of registration requirements. One of the benefits to regulators has been the improvement in the capacity to conduct assessments. Manufacturers have benefited from compiling one package (modules 2-5) for the initial submission as well as a single response package to the consolidated list of questions, which saves time and resources. Respondents were of the view that patients have benefited as the ZaZiBoNa has contributed to an improved availability and accessibility to quality-assured medicines. Some of the challenges identified were the inadequacy of resources and differences in time to the implementation of ZaZiBoNa recommendations by the individual countries. The establishment of a regional unit hosted in one of the member countries to enable centralised submission and coordination was identified as the best strategy to improve the effectiveness and efficiency of the initiative in the interim, with the long-term goal being the establishment of a regional medicines authority. Conclusion: The study identified the strengths of the ZaZiBoNa initiative as well as the opportunities for improvement. The recommendations made would further strengthen this initiative.

Needs-driven talent and competency development for the next generation of regulatory scientists in Africa.

Capacity building programmes for African regulators should link education, training and research with career development in an approach that combines an academic base and experiential learning aligned within a competency framework. A regulatory ecosystem that engages with a broad range of stakeholders will mean that expertise in the ever-expanding field of regulatory science filters into teaching and research in a symbiotic way. In this way capacity development interventions will be a collaborative approach between the learning context (academic and training institutions) and the performance context (regulatory agencies and industry), which will ultimately best serve the patients. Monitoring and evaluation of capacity development interventions will be essential to show value of investments and ultimately guide continued funding and sustainability. This paper reviews the skills and human capacity gaps, reports on regulatory assessment pathways used in Ghana, South Africa and Zimbabwe and outlines a staged tactical approach for Africa that builds on previous efforts to strengthen African regulatory ecosystems.

Comparison of the registration process of the medicines control authority of Zimbabwe with Australia, Canada, Singapore, and Switzerland: benchmarking best practices.

BACKGROUND: Benchmarking regulatory systems of low- and middle-income countries with mature systems provides an opportunity to identify gaps, enhance review quality, and reduce registration timelines, thereby improving patients' access to medicines. The aim of this study was to compare the medicines registration process of the Medicines Control Authority of Zimbabwe (MCAZ) with the regulatory processes in Australia, Canada, Singapore, and Switzerland. METHODS: A questionnaire that standardizes the review process, allowing key milestones, activities and practices of the five regulatory authorities was completed by a senior member of the divisions responsible for issuing marketing authorizations. RESULTS: The MCAZ has far fewer resources than the regulatory authorities in the comparator countries, but employs three review models, which is in line with international best practice. The MCAZ registration process is similar to the comparator countries in key milestones monitored, but differs in the target timelines for these milestones. The MCAZ is comparable to the comparator authorities in implementing the majority of good review practices, although it significantly lags behind in transparency and communication. CONCLUSION: This study identified the MCAZ strengths and opportunities for improvement, which if implemented, will enable the achievement of its vision to be a leading regulatory authority in Africa.

Understanding Quality Paradigm Shifts in the Evolving Pharmaceutical Landscape: Perspectives from the USP Quality Advisory Group.

Recent changes in the pharmaceutical industry have led to significant paradigm shifts in the pharmaceutical quality environment. Globalization of the pharmaceutical industry, increasingly rapid development of novel therapies, and adoption of new manufacturing techniques have presented numerous challenges for the established regulatory framework and quality environment and are impacting the approaches utilized to ensure the quality of pharmaceutical products. Regulators, industry, and standards-setting organizations have begun to recognize the need to rely more on integrated risk-based approaches and to create more nimble and flexible standards to complement these efforts. They also increasingly have recognized that quality needs to be built into systems and processes throughout the lifecycle of the product. Moreover, the recent COVID-19 crisis has emphasized the need to adopt practices that better promote global supply chain resilience. In this paper, the USP Quality Advisory Group explores the various paradigm shifts currently impacting pharmaceutical quality and the approaches that are being taken to adapt to this new environment. Broad adoption of the Analytical Procedure Lifecycle approach, improved data management, and utilization of digital technologies are identified as potential solutions that can help meet the challenges of these quality paradigm shifts. Further discussion and collaboration among stakeholders are needed to pursue these and other solutions that can ensure a continued focus on quality while facilitating pharmaceutical innovation and development.

Evaluation of the Good Review Practices of Countries Participating in the Southern African Development Community: Alignment and Strategies for Moving Forward.

Introduction: National medicines regulatory agencies are faced with challenges including limited resources and technical capacity, resulting in countries collaborating and sharing resources to improve efficiency of the review process to facilitate access to quality-assured medicines by their populations. One such collaboration is the Southern African Development Community (SADC) medicines registration collaborative initiative, ZaZiBoNa. Countries participate in the initiative by contributing to regulatory reviews and good manufacturing practices inspections. The aim of this study was to review and compare the registration processes of regulatory authorities of Mozambique, Namibia, South Africa, Tanzania, Zambia, and Zimbabwe to identify strategies for better alignment. Methods: A senior member of the division responsible for issuing marketing authorisations completed an established and validated questionnaire, which standardises the review process, allowing key milestones, activities and practices of the six regulatory authorities to be identified and compared. The completed questionnaires were validated by the heads of the respective agencies. Results: The six countries vary in population and in the size of their respective regulatory agency and the resources allocated to regulatory reviews. The review processes of the six agencies were similar; however, differences were noted in the milestones recorded; for example, two of the countries did not record the start of the scientific assessment. Additionally, decisions for marketing authorisation were made by an expert committee in four of the countries and by the head of the agency and the Minister of Health in two countries. All six agencies implemented the majority of good review practices; however, the need for improvement in the areas of transparency and communication and quality decision making practices was a common finding for all six countries. Conclusions: Participation in the ZaZiBoNa initiative has improved the way in which the six agencies perform regulatory reviews in their countries, highlighting the realisation of one of the key objectives of the initiative, which was building the expert capacity of member countries. Other agencies in the SADC region and beyond can use the results of this study to identify best practices, which in turn, could improve their regulatory performance.

Evaluation of the Review Models and Approval Timelines of Countries Participating in the Southern African Development Community: Alignment and Strategies for Moving Forward.

Introduction: Regulatory reliance, harmonization and work sharing have grown over the last few years, resulting in greater sharing of work and information among regulators, enabling efficient use of limited resources and preventing duplication of work. Various initiatives on the African continent include ZaZiBoNa, the Southern African Development Community (SADC) collaborative medicines registration initiative. ZaZiBoNa has resulted in great savings in time and resources; however, identified challenges include lack of clear information regarding the participating countries registration processes and requirements as well as lengthy registration times. The aim of this study, therefore, was to compare the data requirements and review models employed in the assessment of applications for registration, the target timelines for key milestones and the metrics of applications received and approved in 2019 and 2020 by Mozambique, Namibia, South Africa, Tanzania, Zambia, and Zimbabwe. Methods: A senior member of the division responsible for issuing marketing authorisations completed an established and validated questionnaire, which standardizes the review process, allowing key milestones, activities and practices of the six regulatory authorities to be identified and compared. The completed questionnaires were validated by the heads of the respective agencies. Results: The majority of applications received and approved by all six agencies in 2019 and 2020 were for generics. The mean approval times for generics varied across the countries, with ranges of 218-890 calendar days in 2019 and 158-696 calendar days in 2020. All three types of scientific assessment review models were used by the six agencies and data requirements and extent of scientific assessment were similar for five countries, while one conducted full reviews for new active substances. A large variation was observed in the targets set by the six agencies for the different milestones as well as overall approval times. Conclusions: The study identified the strengths of the countries as well as opportunities for improvement and alignment. Implementation of the recommendations made as in this study will enhance the countries' individual systems, enabling them to efficiently support the ZaZiBoNa initiative.

Evaluation of the Regulatory Review Process in Zimbabwe: Challenges and Opportunities.

PURPOSE: The aims of this study were to assess the current regulatory review process of the Medicines Control Authority of Zimbabwe (MCAZ), identify key milestones and target timelines, evaluate the overall performance from 2017 to 2019, identify good review practices, evaluate the quality of decision-making processes, and identify the challenges and opportunities for improvement. METHODS: A questionnaire was completed by the MCAZ. The agency has participated in the Optimising Efficiencies in Regulatory Agencies (OpERA) program, a multinational endeavor to characterize assessment procedures and metrics associated with regulatory agencies and regional regulatory initiatives. Data identifying the milestones and overall approval times for all products registered MCAZ from 2017 to 2019 were collected and analyzed. RESULTS: The MCAZ conducts a full review of quality, safety, and efficacy data for generics and biosimilars not approved by a reference agency, an abridged review for products approved by a reference agency and a verification review for World Health Organization prequalified products under the collaborative registration procedure. The highest number of reviewed products is generics manufactured by foreign companies. There has been an improvement in review times for all categories of products over the three-year period. Guidelines, standard operating procedures, and review templates are in place and the majority of indicators for good review practices are implemented. Although quality decision-making practices are implemented, there is no formal framework in place. CONCLUSION: The MCAZ successfully implements three types of review models in line with international standards. Overall, target timelines are realistic and what is achievable with the current available resources. Recommendations made such as the review of available human resources, separation of agency and company time when setting and measuring targets, review of the templates and benefit-risk framework used for abridged review, and development of a decision-making framework present opportunities for an enhanced regulatory review process.

Evaluating the Success of ZaZiBoNa, the Southern African Development Community Collaborative Medicines Registration Initiative.

The Southern African Development Community (SADC) collaborative medicines registration initiative ZaZiBoNa is a successful regional work-sharing initiative on the African continent. This paper reviews the history of the ZaZiBoNa initiative, reflects on what has been realized in six years of operation and what still needs to be achieved. Statistics for the work done by the initiative are available in the literature, but there has not been a critical review of the process, including an analysis of factors contributing to the success of the initiative and conversely those negatively affecting performance. To do this, publicly available literature and statistics, meeting records, terms of reference and unpublished documents belonging to the initiative were reviewed. The successes of the ZaZiBoNa initiative can be attributed to leadership commitment, a clear vision and governance structure providing direction, and a clear, documented operating model, processes and objectives defined from the onset of the initiative. Closure of the gaps that were identified and implementation of the recommendations that were made in this paper will further strengthen the initiative. Furthermore, other regional harmonization or work-sharing initiatives on the African continent and beyond can draw lessons from this review of the ZaZiBoNa initiative for improved efficiency and effectiveness.

Expanding global access to essential medicines: investment priorities for sustainably strengthening medical product regulatory systems.

Access to quality-assured medical products improves health and save lives. However, one third of the world's population lacks timely access to quality-assured medicines while estimates indicate that at least 10% of medicine in low- and middle-income countries (LMICs) are substandard or falsified (SF), costing approximately US$ 31 billion annually. National regulatory authorities are the key government institutions that promote access to quality-assured medicines and combat SF medical products but despite progress, regulatory capacity in LMICs is still insufficient. Continued and increased investment in regulatory system strengthening (RSS) is needed. We have therefore reviewed existing global normative documents and resources and engaged with our networks of global partners and stakeholders to identify three critical challenges being faced by NRAs in LMICs that are limiting access to medical products and impeding detection of and response to SF medicines. The challenges are; implementing value-added regulatory practices that best utilize available resources, a lack of timely access to new, quality medical products, and limited evidence-based data to support post-marketing regulatory actions. To address these challenges, we have identified seven focused strategies; advancing and leveraging convergence and reliance initiatives, institutionalizing sustainability, utilizing risk-based approaches for resource allocation, strengthening registration efficiency and timeliness, strengthening inspection capacity and effectiveness, developing and implementing risk-based post-marketing quality surveillance systems, and strengthening regulatory management of manufacturing variations. These proposed solutions are underpinned by 13 focused recommendations, which we believe, if financed, technically supported and implemented, will lead to stronger health system and as a consequence, positive health outcomes.