Identifying and costing common gaps in Central and West Africa pharmaceutical regulation.

Background: Regulatory systems strengthening is crucial for catalyzing access to safe and effective medical products and health technologies (MPHT) for all. Identifying and addressing common regulatory gaps through regional approaches could be instrumental for the newly incepted African Medicine Agency. Aims: This original study sheds light on common gaps among 10 national regulatory authorities (NRAs) and ways to address them regionally. Objectives: The study used NRA self-assessment outcomes to identify common gaps in four critical regulatory pillars and estimate the cost of addressing them from regional perspectives that aimed at raising the maturity level of regulatory institutions. Methods: A cross-sectional study, using the WHO Global Benchmarking Tool (GBT), was conducted between 2020 and 2021 with five NRAs from ECCAS and ECOWAS member states that use French and Spanish as lingua franca. Results: The 10 NRAs operated in a non-formal-to-reactive approach (ML1-2), which hinders their ability to ensure the quality of MPHT and respond appropriately to public health emergencies. Common gaps were identified in four critical regulatory pillars-good regulatory practices, preparedness for public health emergencies, quality management systems, and substandard and falsified medical products-with overall cost to address gaps estimated at US$3.3 million. Contribution: We elaborated a reproducible method to strengthen regulatory systems at a regional level to improve equitable access to assured-quality MPHT. Our bottom-up approach could be utilized by RECs to address common gaps through common efforts.

Perspectives on systematic capacity building in pharmaceutical regulation for regulators of medical products.

Having a robust, integrated regulatory system is important for ensuring the availability of safe and efficacious medical products of good quality and for protecting public health. However, less than 30% of countries globally have reached the required regulatory maturity level three, with low- and middle-income countries facing challenges in attracting and retaining qualified staff. World Health Organization (WHO) advocates for systematic workforce development, including competency-based education, to address these gaps. We provide perspectives on a systematic approach to capacity building of medicine regulators based on the experience and lessons learnt in developing and piloting the WHO global competency framework for medicine regulators through three scenarios. A systematic approach to capacity building, such as the human performance technology model, can be used to implement the WHO competency framework as part of organizational performance improvement while ensuring that initiatives are well-defined, targeted, and aligned with organizational goals. The competency framework can be used in different contexts, such as improving organization performance for individual regulatory authorities, strengthening regional collaborations, harmonization and reliance on medical products assessment and joint good manufacturing practices inspections of pharmaceutical manufacturers, and developing learning programs for medicine regulators. A competency-based learning approach for regulatory professionals ensures the transfer of learning to the workplace by integrating real-world practices in learning activities and assessments. Further work is required to develop and validate the assessment instruments, apply the competency framework in other contexts, expanding the learning programmes while continuously providing feedback for further refinement of the competency framework and implementation support tools.

Innovative method for rapid detection of falsified COVID-19 vaccines through unopened vials using handheld Spatially Offset Raman Spectroscopy (SORS).

Preventing, detecting, and responding to substandard and falsified vaccines is of critical importance for ensuring the safety, efficacy, and public trust in vaccines. This is of heightened importance in context of public health crisis, such as the COVID-19 pandemic, in which extreme world-wide shortages of vaccines provided a fertile ground for exploitation by falsifiers. Here, a proof-of-concept study explored the feasibility of using a handheld Spatially Offset Raman Spectroscopy (SORS) device to authenticate COVID-19 vaccines through rapid analysis of unopened vaccine vials. The results show that SORS can verify the chemical identity of dominant excipients non-invasively through vaccine vial walls. The ability of SORS to identify potentially falsified COVID-19 vaccines was demonstrated by measurement of surrogates for falsified vaccines contained in vaccine vials. In all cases studied, the SORS technique was able to differentiate between surrogate samples from the genuine COVISHIELD™ vaccine. The genuine vaccines tested included samples from six batches across two manufacturing sites to account for any potential variations between batches or manufacturing sites. Batch and manufacturing site variations were insignificant. In conjunction with existing security features, for example on labels and packaging, SORS provided an intrinsic molecular fingerprint of the dominant excipients of the vaccines. The technique could be extended to other COVID-19 and non-COVID-19 vaccines, as well as other liquid medicines. As handheld and portable SORS devices are commercially available and widely used for other purposes, such as airport security, they are rapidly deployable non-invasive screening tools for vaccine authentication.

Collaborative reliance in medicine safety and quality regulation: Investigation of experiences in handling N-nitrosamine impurities among ZaZiBoNa participating countries.

Introduction: The presence of N-nitrosamine impurities in medicines raised concerns globally as they are genotoxic and probable human carcinogens. A review of N-nitrosamine impurities in medicines provides an opportunity for National Regulatory Authorities (NRAs) to ensure that corrective and preventive actions are applied so that safe and good quality medicines are made available to the public. This study aimed to investigate the experiences on reviews conducted by NRAs from various Southern African Development Community countries which participate in the regional work-sharing forum, ZaZiBoNa, on the quality and safety data due to the presence of N-nitrosamine impurities in medicines. Methods: A comparative, descriptive study using mixed methods was conducted. Purposive sampling was applied in selecting research participants based on their participation status in the ZaZiBoNa initiative. A standardized questionnaire structured into five parts was completed by ZaZiBoNa focal persons/nominated individuals to determine the experience of each NRA in addressing the safety and quality issues related to the presence of N-nitrosamine impurities in the affected medicines. Profiled medicines included sartans, ranitidine, metformin, rifampicin, and rifapentine. Results: Sartan medicines had been reviewed by all countries participating in the ZaZiBoNa initiative. Although most NRAs have yet to conduct reviews on other profiled medicines, evaluations have been implemented to ensure access to safe and good quality medicines within the region. Most countries experienced challenges in communicating with applicants or marketing authorization holders (MAHs) on reviewing N-nitrosamine impurities in their medicines. The majority of NRAs agree that there is a need for further collaboration efforts to review N-nitrosamine impurities in medicines. Conclusion: The review of N-nitrosamine impurities in the profiled medicines by NRAs within the region has demonstrated the importance of enhanced regulatory oversight to safeguard against the risks associated with medicines. Collaborative reliance on the review of the safety and quality of medicine, continuous monitoring, implementation and review of processes, testing methods, and regular engagements with stakeholders could be essential in ensuring adequate control of N-nitrosamine impurities in medicines.

Oxytocin quality: evidence to support updated global recommendations on oxytocin for postpartum hemorrhage.

BACKGROUND: The use of quality injectable oxytocin effectively prevents and treats postpartum hemorrhage, the leading cause of maternal death worldwide. In low- and middle-income countries (LMICs), characteristics of oxytocin-specifically its heat sensitivity-challenge efforts to ensure its quality throughout the health supply chain. In 2019, WHO, UNFPA and UNICEF released a joint-statement to clarify and recommend that oxytocin should be kept in the cold chain (between 2 and 8 °C) during transportation and storage; however, confusion among stakeholders in LMICs persists. OBJECTIVES AND METHODS: To further support recommendations in the WHO/UNFPA/UNICEF joint-statement, this paper reviews results of oxytocin quality testing in LMICs, evaluates product stability considerations for its management and considers quality risks for oxytocin injection throughout the health supply chain. This paper concludes with a set of recommended actions to address the challenges in maintaining quality for a heat sensitive pharmaceutical product. RESULTS: Due to the heat sensitivity of oxytocin, its quality may be degraded at numerous points along the health supply chain including: At the point of manufacture, due to poor quality active pharmaceutical ingredients; lack of sterile manufacturing environments; or low-quality manufacturing processesDuring storage and distribution, due to lack of temperature control in the supply chain, including cold chain at the end user health facilitySafeguarding the quality of oxytocin falls under the purview of national medicines regulatory authorities; however, regulators in LMICs may not adhere to good regulatory practices. CONCLUSIONS: Storing oxytocin from 2 to 8 °C throughout the supply chain is important for maintaining its quality. While short temperature excursions may not harm product quality, the cumulative heat exposure is generally not tracked and leads to degradation. National and sub-national policies must prioritize procurement of quality oxytocin and require its appropriate storage and management.