Registration and Quality Assurance of ARVs and other Essential Medicines in Namibia

Transcription

1 Registration and Quality Assurance of ARVs and other Essential Medicines in Namibia October 2014 September 2015

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5 Registration and Quality Assurance of ARVs and other Essential Medicines in Namibia Nasser Mbaziira Harriet R. Kagoya September 2015

6 Registration and Quality Assurance of ARVs and other Essential Medicines in Namibia This report is made possible by the generous support of the American people through the US Agency for International Development (USAID), under the terms of cooperative agreement number AID-OAA-A The contents are the responsibility of Management Sciences for Health and do not necessarily reflect the views of USAID or the United States Government. About SIAPS The goal of the Systems for Improved Access to Pharmaceuticals and Services (SIAPS) Program is to ensure the availability of quality pharmaceutical products and effective pharmaceutical services to achieve desired health outcomes. Toward this end, the SIAPS result areas include improving governance, building capacity for pharmaceutical management and services, addressing information needed for decision-making in the pharmaceutical sector, strengthening financing strategies and mechanisms to improve access to medicines, and increasing quality pharmaceutical services. Recommended Citation This report may be reproduced if credit is given to SIAPS. Please use the following citation. Mbaziira N, Kagoya HR. (2015). Registration and Quality Assurance of ARVs and other Essential Medicines in Namibia. Submitted to the US Agency for International Development by the Systems for Improved Access to Pharmaceuticals and Services (SIAPS) Program, Arlington, VA: Management Sciences for Health. Key Words Medicines regulation, medicines registration, dossiers, postmarket surveillance Systems for Improved Access to Pharmaceuticals and Services Pharmaceuticals and Health Technologies Group Management Sciences for Health 4301 North Fairfax Drive, Suite 400 Arlington, VA USA Telephone: Fax: Web: ii

7 CONTENTS Acronyms and Abbreviations... iv Acknowledgments... v Background... 1 Interventions... 3 Technical Assistance for the Expedited Registration and Introduction of Newly Recommended ARV Formulations... 3 Results/Outcomes... 5 Performance of NMRC Medicine Registration Function... 5 Conclusions... 9 References Annex A. Official Invitation letter for Participants of Dossier review sessions iii

8 ACRONYMS AND ABBREVIATIONS 3TC ABC ART ARV AZT MNCH MoHSS NMRC NVP QSL SIAPS TB USAID WHO lamivudine abacavir antiretroviral therapy antiretroviral zidovudine maternal, newborn, and child health Ministry of Health and Social Services Namibia Medicines Regulatory Council nevirapine Quality Surveillance Laboratory Systems for Improved Access to Pharmaceuticals and Services tuberculosis US Agency for International Development World Health Organization iv

9 ACKNOWLEDGMENTS The authors acknowledge the staff of the Namibia Medicines Regulatory Council (NMRC) secretariat for their efforts, dedication, and enthusiasm that led to the achievements in medicines regulation during this project. We are also grateful to the Registrar of the NMRC, Mr. Johannes Gaeseb, for his time and support throughout the implementation of technical assistance activities for medicines regulation. We acknowledge the management, technical, and operations/administration staff of the Systems for Improved Access to Pharmaceuticals and Services (SIAPS) Program in Namibia for the support rendered in implementing the activities in this report. Finally, we acknowledge the financial support provided by the President's Emergency Plan for AIDS Relief through the US Agency for International Development (USAID), without which implementation of the activities during this period would not have been possible. v

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11 # of dossiers BACKGROUND Namibia s estimated 2.3 million people are distributed unevenly in urban centers and rural communities, and the country has a sparse population density of 2.6 people/square kilometer. Namibia is among the African countries most significantly affected by the HIV and AIDS epidemic, which is one of the leading causes of morbidity and mortality in the country. The adult HIV prevalence rate was estimated at approximately 14.2%, and more than 140,000 patients were on antiretroviral therapy (ART) as of March The NMRC is mandated to ensure the quality, safety, and efficacy of medicines and contributes to improving treatment outcomes and the health of Namibia s population and economy. Key functions of the NMRC include conducting technical assessments of medicines applications prior to registration and postmarket surveillance to monitor the quality of registered medicines in the country. Namibia s NMRC secretariat has benefited greatly from the technical and financial support of USAID-funded projects, including Rational Pharmaceutical Management Plus, Strengthening Pharmaceutical Systems, and currently SIAPS. All of these projects have worked to improve and strengthen the NMRC s capacity to efficiently and effectively perform its statutory regulatory functions to support HIV and AIDS and other public health services by ensuring the quality, safety, and efficacy of antiretrovirals (ARVs) and other essential medicines for ART. Over the years, the NMRC has received support for registration, inspection and licensing, quality surveillance, therapeutics information, and pharmacovigilance. The effectiveness of NMRC s functionality has been greatly limited by human and technical resource constraints, which contributed to the rapid growth of the number of unassessed medicines applications/dossiers. By March 2014, there was a backlog of 746 dossiers. This had a significant impact on the HIV commodities supply chain as new ARVs, which were not yet registered, could not easily be procured and stocked by the central medical stores, and the quality, safety, and efficacy of those medicines that received waivers could not be guaranteed. Figure 1 illustrates the backlog trend over a four-year period. On average, more than 40% of the received dossiers were not reviewed, including 64% in 2011, 49% in 2012, 44% in 2013, and 45% by September Received Backlog Source: Pharmadex, September 2014 Figure 1. Number of received and unevaluated/backlog dossiers,

12 Registration and Quality Assurance of ARVs and other Essential Medicines in Namibia With support from SIAPS, an improvement in the percentage of application dossiers reviewed annually was observed (figure 2). 60% 51% 56% 50% 40% 36% 30% 20% 10% 0% Source: Pharmadex. Namibia Ministry of Health and Social Services (MoHSS), March Figure 2. Percentage of dossiers evaluated vs. those received by the NMRC SIAPS-supported interventions in FY14 included capacity building through training and mentoring. Priority was given to reviewing the more than 550 applications that made up the backlog of dossiers. At the NMRC, the Therapeutics Information and Pharmacovigilance Center performs relatively well in terms of maintaining an effective pharmacovigilance system, particularly in the areas of adverse drug reaction/event monitoring and disseminating information on medicines usage to Namibian health care providers for patient safety. However, monitoring the quality of medicines in the public supply chain to rule out counterfeit and substandard medicines was still a challenge that could pose a risk of circulating substandard and counterfeit pharmaceuticals that may negatively affect treatment outcomes for HIV and AIDS, tuberculosis (TB), and other diseases. 2

13 INTERVENTIONS Technical Assistance for the Expedited Registration and Introduction of Newly Recommended ARV Formulations In FY15 (October 2014 September 2015), SIAPS continued to provide technical assistance to facilitate the expedited assessment and registration of new and existing ARV formulations to support the implementation of the revised Namibian ART guidelines (dated January 2014). The technical assistance focused on improving the efficiency of the regulatory system so that the recommended new first-line fixed-dose combination ARVs that contain tenofovir and emtricitabine for adults; optimized ARV formulations for pediatric use; and other medicines for HIV and AIDS; TB; maternal, newborn, and child health (MNCH); and other public health diseases are assessed and considered for registration and made available for public procurement in a timely manner to benefit patients undergoing ART. SIAPS provided technical assistance in the form of mentoring and ongoing on-the-job training to five new NMRC staff and other personnel engaged in evaluating dossiers for the registration of ARVs, including new pediatric formulations, and other essential medicines. This was conducted during organized dossier evaluation sessions that were gradually transitioned to the NMRC for sustainability and continued improvement of the institution s operational efficiency. To further ensure the quality, safe, and efficacy of HIV and AIDS, TB, MNCH, and other essential medicines after registration, the NMRC, with support from the USAID-funded SIAPS Program, developed medicines quality monitoring guidelines. In FY15, the NMRC collaborated with SIAPS to conduct a baseline survey of the quality of ARVs and TB and other essential medicines in public health facilities using the newly developed guidelines. The activity benefitted eight (57%) of the 14 regions (Kavango East and West were considered one region) in the country. Samples were tested by the national Quality Surveillance Laboratory (QSL), and those failing the pharmacopeial tests were forwarded to a World Health Organization (WHO) prequalified laboratory for confirmatory testing. Table 1 shows the scope of samples collected. Table 1. Medicine Samples Collected # Category Generic name Strength Dosage form 1 ARV Abacavir/lamivudine (ABC/3TC) 60mg/30mg Tablets 2 OI Amoxicillin 250mg Capsules 3 OI Amoxicillin 125mg/ml Suspension 4 OI Amoxicillin/clavulanic acid 1,000mg Tablets 5 OI Cefuroxime axetil 125mg/5ml Suspension 6 OI Cefuroxime axetil 250mg Tablets 7 OI Co-trimoxazole 240mg/5ml Suspension 8 OI Co-trimoxazole 480mg Tablets 9 ARV Lamivudine/zidovudine (3TC/AZT) 150mg/300mg Tablets 10 ARV Lamivudine/zidovudine (3TC/AZT) 30mg/60mg Tablets 11 Other Metformin 500mg Tablets 12 ARV Nevirapine (NVP) 50mg/ml Oral solution 13 ARV Nevirapine (NVP) 200mg Tablets 14 Other Perindopril 4mg Tablets 15 TB RHZE 150/75/400/275mg Tablets 3

14 Registration and Quality Assurance of ARVs and other Essential Medicines in Namibia Figure 3. Medicines application dossiers lined up for review during a dossier evaluation session, October 2014 (Photo by MSH/Namibia) Figure 4. Ms. Wubijig Legesse (right) reviews a dossier, October 2014 (Photo by MSH/Namibia) 4

15 Percent of backlog at the given time Number of Dossiers RESULTS/OUTCOMES Performance of NMRC Medicines Registration Function In October 2014, SIAPS supported the NMRC to organize a dossier evaluation session primarily aimed at mentoring and improving dossier evaluation skills for newly recruited NMRC staff and reducing the dossier backlog. A total of 132 medicines registration applications received in 2011 and 2012 were reviewed. This activity was successfully transitioned to the NMRC, which organized four evaluation sessions in FY15. This significantly decreased the size of the backlog Received Backlog, Sept 2014 Backlog, Sept 2015 Figure 5. Trends in the medicines registration application backlog There was a significant decrease in the size of the dossier backlog at the NMRC (figure 5). A total of 711 applications received between 2011 and 2014 had not been evaluated for registration by September 2014 (FY14), compared to 100 applications as of September 2015 (FY15), an 86% reduction. The length of the backlog also decreased significantly between FY14 and FY15 (figure 6). In 2015, 40% of the dossiers received were reviewed. 40% 38% In FY14 In FY15 30% 20% 24% 18% 19% 10% 0% 8% 3% 2% 1% > three years > two years > one year < one year Length of backlog Figure 6. Length of backlog of dossiers in FY14 and FY15 5

16 Number of samples Registration and Quality Assurance of ARVs and other Essential Medicines in Namibia As of August 2015, 6,064 pharmaceutical products were registered for use, and the average number of days taken to review and approve a medicine registration application decreased from more than 53 days to 48 days in Postmarket Surveillance and Medicines Quality Monitoring A total of 172 samples of ARVs and TB and other essential medicines were collected from 24 public health facilities in eight regions. The facilities included ten primary health care clinics, five health centers, eight district hospitals, and one intermediate hospital. Figures 7 and 8 show the total number of samples collected categorized by generic name and region, respectively Figure 7. Number of samples collected by generic name categories Zambezi 6 Erongo 10 Karas 18 Kavango Otjozondjupa Oshikoto Ohangwena 30 Oshana Number of medicines samples Figure 8. Number of samples collected by region 6

17 Results/Outcomes Table 2 shows the improved capacity of the QSL to test medicines samples. The laboratory was able to test and release the results of 88% (151) of the samples collected. This may be partly attributed to SIAPS support for human capacity development at the NMRC in FY14. There was also a challenge of availability of reference standards for samples with zero percent rate. Table 2. Percentage of Samples with Results from NMRC QSL # Generic name Strength Dosage form # of sample % results received 1 ABC/3TC 60mg/30mg Tablets 3 0% 2 Amoxicillin 250mg Capsules 21 95% 3 Amoxicillin 125mg/ml Suspension 16 88% 4 Amoxicillin/clavulanic acid 1000mg Tablets 5 100% 5 Cefuroxime axetil 125mg/5ml Suspension 6 100% 6 Cefuroxime axetil 250mg Tablets 5 100% 7 Co-trimoxazole 240mg/5ml Suspension 17 94% 8 Co-trimoxazole 480mg Tablets % 9 3TC/AZT 150mg/300mg Tablets 13 77% 10 3TC/AZT 30mg/60mg Tablets 5 100% 11 Metformin 500mg Tablets % 12 NVP 50mg/ml Oral solution 8 100% 13 NVP 200mg Tablets 14 86% 14 Perindopril 4 Tablets 8 0% 15 RHZ m150/75/400/275m Tablets % E Total g % Of the 151 samples tested, 13.9% (21) did not conform to pharmacopeial specifications. Table 3 illustrates the results of the samples by region. Notably, 36.8% of the samples were unregistered, of which 1.9% were substandard according to the results from QSL and a WHO prequalified laboratory. Table 3. Sample Results by Region Region Passed Failed Not tested Total Erongo Karas Kavango Ohangwena Oshana Oshikoto Otjozondjupa Zambezi Total Figures 9 and 10 provide further analyses on the failures experienced during testing. 7

18 Number of samples Registration and Quality Assurance of ARVs and other Essential Medicines in Namibia 120% 100% 100% 80% 60% 40% 20% 0% 0% 7% 0% 0% 0% 17% 0% 0% 0% 0% 0% 0% Figure 9. Percentage of failures by product category Amoxicillin Susp Co-trimoxazole Susp Co-trimoxazole Tabs Assay Dissolution Others Analytical test Figure 10. Number of sample failures by analytical parameters 8

19 CONCLUSIONS SIAPS continued technical assistance to the NMRC strengthened its capacity, improved efficiency, and significantly decreased the backlog of medicines registration applications. The NMRC took responsibility for financial support for intensified medicines dossier reviews to accelerate the process and shorten the time needed to evaluate applications and register medicines. Three of the four dossier review sessions held in FY15 were organized and financed by the NMRC, which showed the organization s commitment and the sustainability of the interventions supported by USAID through SIAPS. The NMRC also made great strides towards postregistration monitoring of medicines quality. Regulatory decisions are taken based on the outcomes of postmarket samples tested. Decisions may include the NMRC recalling all products that do not conform to specifications, which may lack efficacy, affect treatment outcomes, and increase the risk of developing microbial resistance to medicines. 9

20 REFERENCES Anisfeld M, An L, Mbaziira N, Kagoya H, Sagwa E Strengthening the Capacity of the Namibia Medicines Regulatory Council in the Regulation of Antiretroviral Medicines and Other Essential Pharmaceutical. Submitted to the US Agency for International Development by the Systems for Improved Access to Pharmaceuticals and Services (SIAPS) Program, Arlington, VA: Management Sciences for Health Namibian Medicines and Related Substances and Control Act of 2003 National Guidelines for Antiretroviral Therapy, fourth Edition, January 2014, MoHSS, Namibia Systems for Improved Access to Pharmaceuticals and Services Namibia Work Plan: October 1, 2014 September 30,

21 ANNEX A. OFFICIAL INVITATION LETTER FOR PARTICIPANTS OF DOSSIER REVIEW SESSIONS 11