For the purpose of this paper, findings are categorised into five (5) main catogories namely policy and legal framework; NMRA governance; medicines registration and good manufacturing practice (GMP) systems; quality management systemss and information management systems.
Figure 3. 1: The Status of National Medicines Policies and Medicines Laws in the EAC region; 2010/11 – 2015/2016
Table 3. 1 Policy and Legal Frameworks in the EAC Partner States; 2010/11 – 2015/16
Governance: A baseline study revealed that, TMDA, ZFDB and Kenya Pharmacy and Poisons Board (PPB) were semi-autonomous entities and that the head of PPB also served as a Chief Pharmacist combining both regulatory and policy roles as the technical arm of the Ministry of Health [29,30]. For Rwanda and Burundi, regulatory functions were administered by the respective Ministries of Health Departments. For TMDA (Tanzania), KPPB (Kenya) and the NDA (Uganda), the agencies had powers to charge fees for regulatory services and received very little or no government subvention [29,30].
This study has shown a significant improvement in the level of autonomy of NMRAs. Currently; four (4) NMRAs are operating as semi-autonomous agencies namely; the Rwanda Food and Drugs Authority (RFDA), TMDA (for Tanzania mainland), Zanzibar Food and Drug Agency (ZFDA), Kenya Pharmacy and Poisons Board; while Uganda National Drugs Authority (NDA), is fully autonomous. Furthermore, the National Pharmaceuticals Regulation Law of Burundi which was under consideration by the national Parliament provides for the establishment of a semi-autonomous NMRA to be called Drug and Food Regulatory Authority of Burundi (ABREMA) [44]. Table 3.2 provides analysis of the NMRAs governance framework including the level of autonomy.
There is a progressive trend in the development of regulations and guidelines in the EAC Partner States (Table 3.3 and Figure 3.2). While baseline data showed three out of the six (50%) NMRAs had regulations and guidelines, in end-line data, 5 of 6 NMRAs (83%) reported having regulations and guidelines in place.
Table 3. 3 Regulations and Guidelines in the EAC Partner States; 2011/12 – 2014/15
Figure 3. 2 Trends in developing regulations and guidelines in the EAC Partner States (excluding Burundi); 2011/12 – 2014/15
Medicines registration system: Comparison of baseline data show improvement in registration system in Rwanda and Burundi. All the six (6) NMRAs now have a legal mandate to register medicines and have a system to manage applications from receipt of dossier to the issuance of marketing authorization. In addition, all the NMRAs use the EAC harmonized guidelines for registration and standard operating procedures (SoPs) for joint review of dossiers. All NMRA participate in the EAC joint review of dossiers. However, the time taken to register a product based on the outcome of the joint review process varies from country to country. For instance, out of fifteen (15) applications which were received through the regional procedure, TMDA registered all the products; KPPB 13/15; Burundi 1/15; Rwanda 9/15; Zanzibar 1/15, and Uganda 7/15. There is need to study factors hampering national uptake of joint review process as it has an impact on marketing authorization timelines. Reliance mechanisms exist in Kenya, Tanzania-Mainland, Tanzania-Zanzibar and Uganda while it was not the case for Burundi and Rwanda.
GMP Inspection System: All six (6) NMRAs have a legal mandate to conduct GMP inspection. Except for Burundi NMRA, all the remaining NMRAs reported conducting inspections of manufacturing sites. While Kenya, Tanzania and Uganda NMRAs have conducted inspections since baseline study, Rwanda and Zanzibar NMRAs only started in 2015. With exception of Burundi, all the NMRAs indicated using EAC Harmonized guidelines for GMP inspection from 2015 when they came into force. Each NMRA reported having participated at least once in the EAC joint inspections. Rwanda, Uganda and Zanzibar employ a reliance models by using GMP inspection reports from other ag such as EAC, SRAs, PICs, US-FDA, and/or WHO-PQ Programme. Table 3.4 is a detailed analysis of the status of registration and GMP inspection system in the 6 NMRAs in the EAC region.
Table 3. 4 Medicines Registration and GMP Inspection Systems in the EAC Partner States NMRAs; 2011/12 – 2015/16
Table 3.5 provides detailed results on the status of each of the EAC NMRAs system for registration of medicines. The highest five years average of 800 new applications were received by the Tanzania-Mainland NMRA, followed by Uganda (458), Burundi (70) and Zanzibar (16). There was no data for Kenya and Rwanda for the reported period.
Table 3. 5 Medicines Registration System in the EAC Partner States NMRAs; 2011/12 – 2015/16
Secondary data shows that with the initial target to have 75 medicines registered by TFDA, NDA & PPB by end of yr 5, the 3 NMRAs have exceeded the target with their respective numbers indicated in brackets, TMDA (237), Kenya PPB (1676) and Uganda NDA (612) [45]. With a target of 100 applications to be submitted to NMRAs using EAC CTD by end of yr 5; TMDA had received 1266 applications, Uganda NDA-2147; Kenya PPB-2475; ZFDA-76; PTF-792; and DPML -447. For EAC NRAs with limited capacity, the target was to register 50 products and the outcome is as follows; ZFDA (42), which is 85 % of the target, PTF registered 297 i.e. over 100% of target while DPML registered 10 products (20% of the target).
Report of the joint review process shows that out of the forty-nine (49) applications received, 38 applications were jointly evaluated including eight (8) Anti-Cancer, Anti-TB and Anti-Biotics. The products include Avastin Inj (100/4ml,400/16ml); Herceptin injection (150mg & 440mg); Nexavar Tabs 200mg; Sirturo Tabs 100mg; Cetuximab 5mg/ml (Soln for Infusion); and Kemoxyl DT 250 Disp Tabs and they granted marketing authorization withing 5-7 months following receipt of the application [66]. In addition, all the EAC Partner States NMRAs domesticated the EAC GMP Guideline and conducted fourteen (14) Joint GMP Inspections in various countries including Egypt, Kenya, India, Uganda, Tanzania, and Morocco with ten (10) facilities meeting GMP Standards and issued with Certificate of Compliance [45]. The median timeline from dossier submissions to national marketing authorization in the EAC region was reduced to seven (7) months since implementation of joint dossier assessments compared to the previous 1 – 2 years [19].
Functional information management systems: One of the EAC MRH Objectives is to have all the Partner States’ NMRAs implementing common information management system (IMS) for medicines registration in each of the EAC Partner States’ NMRAs which is linked in all Partner States and the EAC Secretariat. A robust IMS is key for supporting the technical aspects of medicines regulation to facilitate efficiency and effectiveness of business processes, improve transparency; facilitate decision-making process, sharing and exchange of information among NMRAs and stakeholders; and timeliness of approval of registration decisions. During the baseline survey in 2010/11, Tanzania-Mainland had an integrated system which was locally developed, and Kenya used SIAMED®. Uganda, on the other hand, used a combination of SIAMED®, ACCESS® and a locally developed software. Burundi had a manual IMS which was not functioning, Zanzibar had a functional manual registry and Rwanda had both a manual and electronic system. The method of capturing information in NMRA’s in the EAC Partner States was variable and unreliable, the electronic systems were not user friendly, they were difficult to integrate with other IMS platforms and could not automatically generate/print certificates or be linked to websites, and the manual systems were labour intensive.
A comparison of IMS implementation status with baseline data shows a significant improvement in all the countries with Burundi and Zanzibar moving from manual to electronic systems. All the EAC NMRAs are now using a harmonized IMS with 5 out of 6 NMRAs sharing regulatory information amongst each other as indicated in Table 3.6 and Figure 3.3.
Table 3. 6 Different Levels of IMS Implementation by the EAC Partner Sates NMRAs; 2011/12 – 2015/16
Figure 3. 3 The Status of Implementation of Information Management Systems in the EAC Partner States NMRAs (2016)
Table 3. 7 Information Management System in the East African Community Partner States National Medicines Regulatory Authorities (2016)
Functional quality management system: ISO certification is a globally recognized accreditation of the maturity and functionality of the quality management system (QMS) of an organization, including medical products regulatory agencies. EAC MRH Projects advocates for implementation of QMS to facilitate delivery of quality and consistent services to customers. Zanzibar, Burundi, Rwanda and Kenya had no QMS during baseline survey, TMDA was ISO 9001:2008 certified and Uganda had initiated the ISO certification process. Evaluation of QMS implementation data from the EAC Partner States NMRAs indicated different levels of implementation as indicated in Table 3.7.
Table 3.7 Functional Quality Management System in the EAC Partner States NMRAs; 2011/12 – 2014/15
To date, Kenya, Tanzania, Zanzibar and Uganda’s NMRAs are 9001:2015 ISO-certified, while Rwanda and Burundi are working toward 9001:2015 ISO certification. It is also important to recognise the achievement made by Kenya, Uganda and Zanzibar considering there was no QMS at baseline. PTF (Rwanda) is moving directly toward the attainment of the ISO 9001:2015 certifications while DPML (Burundi) implemented Quality Objectives and Standard Operating Procedures for some regulatory activities, including Medicines Evaluation and Registration.