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.
Table 2 Status of indicators under policy and legal frameworks category (2010/11 – 2015/16)
Governance: A baseline study revealed that, the TMDA (Tanzania), ZFDB (Zanzibar) and PPB (Kenya) 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 . For Rwanda and Burundi, the respective Ministries of Health Departments administered regulatory functions. For TMDA (Tanzania), PPB (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 provides analysis of the NMRAs governance framework including the level of autonomy.
Moreover, with there was a progressive trend in the development of regulations and guidelines in the EAC Partner States (Figure 1). 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 Status of indicators NMRA governance category (2010/11 – 2015/16)
Fig. 1 Trends in developing regulations and guidelines (Indicator 4) in the EAC Partner States (excluding Burundi) (2011/12 – 2014/15)
Medicines registration system: Comparison of baseline data show improvement in registration systems in Rwanda and Burundi. All 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 (Table 4). 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 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) (Table 4). There is need to study factors hampering national uptake of joint review process as it has an impact on marketing authorization timelines. A reliance mechanism (where an agency relies on others in making a regulatory decision) exists in Kenya, Tanzania-Mainland, Tanzania-Zanzibar and Uganda while it was not the case for Burundi and Rwanda. Results on number of products applications received per annum in (Table 4, under indicator 8) indicated 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). Kenya and Rwanda indicated to have received 1030 and 833 applications respectively in 2016.
Table 4 Medicines Registration and GMP Inspection Systems in the EAC Partner States NMRAs (2011/12 – 2015/16)
Secondary data shows the initial target of having at least 75 medicines registered by the NMRAs with stronger capacity, namely TFDA, NDA and PPB by the end of year 5. These NMRAs exceeded the target by registering 237, 612 and 1676 medicines respectively at the end to the stated period [45]. The NMRAs with a lower capacity in Zanzibar, Rwanda and Burundi, had a target of registering 50 medicines each, whereby they registered 42, 297 and 10 medicines respectively at the end of the stated period. Moreover, with a target of receiving 100 applications prepared as per the EAC CTD by end of year 5, the number of applications received by the NMRAs were 1266 (Tanzania), 2147 (Uganda), 2475 (Kenya), 76 (Zanzibar), 792 (Rwanda) and 447 (Burundi).
Report of the joint review process shows that out of the forty-nine (49) applications received, 38 applications were jointly evaluated and granted marketing authorization within 5 to 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].
GMP Inspection System: All six (6) NMRAs have a legal mandate to conduct GMP inspection (Table 4, indicator 11). Except for Burundi NMRA, the remaining NMRAs reported to be conducting inspections of manufacturing sites. While Kenya, Tanzania and Uganda NMRAs had conducted inspections since during the baseline study, Rwanda and Zanzibar NMRAs only started in 2015. Moreover, All NMRAs indicated to be using the 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. In addition, Rwanda, Uganda and Zanzibar employ a reliance models by using GMP inspection reports from other agencies such as EAC, SRAs, PICs, US-FDA, and/or WHO-PQ Programme (Table 4).
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 5.
Table 5 Status of the 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.
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 NMRAs in the EAC Partner States was variable and unreliable. The electronic systems were not user friendly, difficult to integrate with other IMS platforms, could not automatically generate or print certificates or be linked to websites. The existed 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 Figure 2 and Table 6.
Fig. 2 Status of Implementation of Information Management Systems in the EAC Partner States NMRAs (2010/11 – 2015/2016)
Table 6 Status of implementation of different key modules by the NMRAs under Information Management Systems (IMS) category in by 2015