Regulation of medical diagnostics and medical devices in the East African community partner states

Background Medical devices and in vitro diagnostic tests (IVD) are vital components of health delivery systems but access to these important tools is often limited in Africa. The regulation of health commodities by National Regulatory Authorities is intended to ensure their safety and quality whilst ensuring timely access to beneficial new products. Streamlining and harmonizing regulatory processes may reduce delays and unnecessary expense and improve access to new products. Whereas pharmaceutical products are widely regulated less attention has been placed on the regulation of other health products. A study was undertaken to assess regulation of medical diagnostics and medical devices across Partner States of the East African Community (EAC). Methods Data was collected during October 2012 through desk based review of documents and field research, including face to face interviews with the assistance of a structured questionnaire with closed and open ended questions. Key areas addressed were (i) existence and role of National Regulatory Authorities; (ii) policy and legal framework for regulation; (iii) premarket control; (iv) marketing controls; (v) post-marketing control and vigilance; (vi) country capacity for regulation; (vii) country capacity for evaluation studies for IVD and (viii) priorities and capacity building for harmonization in EAC Partner States. Results Control of medical devices and IVDs in EAC Partner States is largely confined to national disease programmes such as tuberculosis, HIV and malaria. National Regulatory Authorities for pharmaceutical products do not have the capacity to regulate medical devices and in some countries laboratory based organisations are mandated to ensure quality of products used. Some activities to evaluate IVDs are performed in research laboratories but post market surveillance is rare. Training in key areas is considered essential to strengthening regulatory capacity for IVDs and other medical devices. Conclusions Regulation of medical devices and in vitro diagnostics has been neglected in EAC Partner States. Regulation is weak across the region, and although the majority of States have a legal mandate to regulate medical devices there is limited capacity to do so. Streamlining regulation in the EAC is seen as a positive aspiration with diagnostic tests considered a priority area for harmonisation. Electronic supplementary material The online version of this article (doi:10.1186/s12913-014-0524-2) contains supplementary material, which is available to authorized users.


Background
The East African Community (EAC) is a regional intergovernmental organization of five Partner States, namely the Republic of Kenya, the Republic of Uganda, the Republic of Burundi, the Republic of Rwanda and the United Republic of Tanzania. Together the five states cover an area of approximately 1.8 million square kilometres and a population of over 135 million people. In addition to promoting trade and economic growth a priority consideration for the EAC is the health of the population. Health indicators across the region show increasing life expectancies [1] but despite progress made the region remains beset by conditions such as tuberculosis, HIV/AIDS, other sexually transmitted infections and in some geographic areas malaria [2][3][4]. The 1999 founding Treaty for the Establishment of the East African Community articulates a policy to "harmonize national health policies and regulations and promoting the exchange of information on health issues in order to achieve quality health within the Community" [5]. A program to harmonize registration of medicines within EAC Partner States was launched in 2012 under the leadership of the EAC Medicines and Food Safety Unit [6]. The project forms part of a wider programme, the African Medicines Regulatory Harmonisation (AMRH) Initiative which is coordinated by the African Union's New Partnership for Africa's Development (NEPAD). The overall aim of the AMRH Programme is to improve public health in Africa by increasing access to good quality, safe and effective medicines through the harmonization of medicines regulations, including reduction of the time taken to register essential medicines for the treatment of diseases [6].
In addition to medicines other medical products of benefit to patients include medical devices and diagnostic tests. Such products make a major contribution to health as many important diseases and conditions require diagnostic guidance to ensure appropriate care. This includes therapeutic use of drugs, where delayed diagnosis can result in deterioration of the patient and, for infectious conditions, continued transmission and spread of disease. The regulation of products for human health by National Regulatory Authorities (NRAs) is intended to ensure their safety and quality whilst ensuring timely access to beneficial new products. Safety may be assured by pre-market scrutiny of new products and by post-market surveillance to ensure quality and performance are maintained. Regulatory controls imposed should be proportionate to the risk of harm to individual or public health. The market dynamics for medical devices and diagnostic products for health are distinct from those for pharmaceutical products and their regulation requires a different approach to that for medicines. Medical devices present a wide range of technologies, ranging from the simple band aid to very complex machinery. Quality of design and manufacture is important, particularly for devices that use electrical power where a malfunction could cause serious injury or death or for products that use toxic reagents or expose the user to risk of infection.
Diagnostic tests vary in complexity, ranging from simple colorimetric dip-stick devices to sophisticated computerised instruments and for some conditions there is a proliferation of products suitable for use at different levels of the healthcare delivery system. Most diagnostic tests fall into the category of in vitro diagnostics (IVDs), where they are used to test specimens obtained from the patient. Unlike medicines or vaccines the product is not ingested and the risk of causing harm is related to the performance of the device and likelihood of a malfunction and the consequences of obtaining an incorrect test result. The Global Harmonization Task Force have recommended a four tier risk classification system for medical devices and diagnostics where risk is defined as the combination of the probability of occurrence of harm and the severity of that harm [7].
Reagents such as microbiological stains or culture media fall into the lowest category as they pose little hazard whereas for tests used to screen blood products for deadly diseases such as HIV an incorrect result could have serious consequences, including onward transmission of the disease. Such high risk products require more stringent regulation, including studies of clinical performance to determine their efficacy in the target population.
Access to IVDs and other medical devices in developing countries is currently limited by their availability and cost and in addition many diagnostic tests require laboratory facilities and trained personnel that are not readily available in Africa. A new generation of devices are being developed for diagnosing important diseases that promise significant benefit to public health. These include tests for use at point-of-care that do not require referral to specialist facilities [8]. It is important that patients in developing countries have timely access to these products and that they are made available at affordable prices. Regulation of medical devices in developing countries is weak and this is particularly a problem with diagnostic tests [9]. In countries that do not regulate IVDs, they may be sold with little or no evidence of their efficacy. Where controls do occur they can act as a barrier to products entering the country [10]. An example is the delayed marketing of a point-of-care device for enumerating CD4 cells to enable patients with HIV to access therapy. The requirement for clinical trials in individual countries has resulted in considerable duplication of effort with little or no scientific gain, and has increased costs and delayed their introduction in some African countries by years.
In accordance with EAC policy to improve public health through harmonized regulation, a regional survey was undertaken during 2012 of the regulation of medical diagnostics and medical devices in the East African Community Partner States. The aim of the survey was to assess capacity and current practices across the Partner States for regulation of medical diagnostics (including In-vitro Diagnostics) and medical devices and the capacity to undertake pre and post market assessment of quality, safety and effectiveness. We hereby report the findings of the study and recommendations made following review of the data by a panel of technical experts drawn from EAC partner states.

Methods
Data was collected during October 2012 through desk based review and field research, including face to face interviews. Information was collected with the assistance of a structured questionnaire containing both closed and open ended questions [see Additional file 1: Appendix S2 for detailed questionnaire]. Questions were framed to collect data on each of the essential features of a regulatory program for medical devices as described in guidelines published by the World Health Organisation [11]. The questionnaire addressed in vitro diagnostic devices and medical devices using the following definitions adapted from guidance issued by the Global Harmonization Task Force, a voluntary group of representatives from medical device regulatory authorities and trade associations from Europe, the United States of America (USA), Canada, Japan and Australia [12].
A medical device (MD) is an instrument, apparatus, implant, in vitro reagent, or other similar or related article, which is intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, or intended to affect the structure or any function of the body and which does not achieve any of its primary intended purposes through chemical action within or on the body.
An 'in vitro diagnostic device' (IVD) is a medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, equipment, or system, whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body, solely or principally for the purpose of providing information concerning a physiological or pathological state.
Key areas addressed were (i) existence and role of National Regulatory Authorities; (ii) policy and legal framework for regulation; (iii) premarket control; (iv) marketing controls; (v) post-marketing control and vigilance; (vi) country capacity for regulation; (vii) country capacity for evaluation studies for IVD and (viii) priorities and capacity building for harmonization in EAC Member States.
Each Partner State was visited to enable interview with key stakeholders. Interviewees were selected on the recommendation of country experts. Both mainland Tanzania and the semi-autonomous territory of Zanzibar were consulted. Where experts were not available for interview information was sourced from documented evidence. In addition to the completed questionnaires written reports were received from country experts. Information sources used in the study are summarised in Table 1 and a list of documents accessed is available in the Additional file 2: Table S1.
Following compilation, the data was reviewed by a panel of experts from the Republic of Kenya, the Republic of Uganda, the Republic of Burundi and the United Republic of Tanzania (Mainland and Zanzibar), including representatives of Ministries of Health, National Regulatory Authorities, National Medical Laboratories and Public Health Regulatory Authorities. Representatives of medical diagnostics manufacturers were also present.
Ethical review was not applicable to this study which accessed and collated information in the public domain.
No 'study subjects' participated in the study, no human data or materials were collected and no interventions

Results and discussion
Reports were compiled from all five partner States. A total of 24 interviews were conducted representing 16 organisations and 47 documents were collated ( Table 1).

Legislative and policy framework
Four Member States, Burundi, Kenya, Rwanda and Tanzania (Mainland and Zanzibar) reported legislation in the form of Acts of Parliament addressing products for health, including medical diagnostics and medical devices ( Table 2). Both Kenya and Tanzania Mainland reported legislative inconsistencies relating to medical devices used in laboratories, with some duel responsibility for their control. The fifth Partner State, Uganda has legislation regarding the control of drugs (National Drug Policy and Authority Act 1993) but no provision for the regulation of medical products other than general legislation for all commodities which are defined as 'any article, product or thing which is or will ultimately be the subject of trade or use'. (The Uganda National Bureau Of Standards Act 1983). However, guidelines on use of medical diagnostic products are being developed by the Allied Health Professionals Council (AHPC) of Uganda. The AHPC is mandated by an Act of Parliament to regulate medical laboratory professionals (among other Allied Health Professional workers) and any other matter related to the practice of the professionals.
All EAC Partner States identified one or more regulatory bodies for medical products with the exception of Rwanda that has instigated a taskforce to oversee the establishment of a Food and Drug Authority. Whereas in all States medicines are regulated by either a Pharmacy Board or a Food and Drugs Authority there is little capacity for regulation of medical devices or IVDs. Where medical devices are controlled it is largely within disease specific programmes such as tuberculosis, malaria or HIV/AIDS with the Department of Health or international donors guiding procurement decisions rather than guidance from a national regulatory authority. Two lists of approved products were supplied by respondents to the questionnaire. The Private Health Laboratories Board in Tanzania list included IVDs for HIV, malaria, hepatitis and syphilis and a number of Haematology and Chemistry Analysers. The Kenyan National AIDS and STI Control Programme (NASCOP) provided a list of diagnostic products approved for HIV, hepatitis B and C and syphilis. One country, Tanzania, reported that public procurement was linked to regulation through consultation with the Private Health Laboratories Board. Both Burundi and Uganda require authorization of importation.
Some countries reported dual responsibility for diagnostic devices where more than one agency is mandated and some tensions were evident between laboratory-based organizations who evaluate diagnostic test performance and agencies whose primary activities lie in the regulation of medicines. Although the focus of regulatory activities was pharmaceuticals some countries are taking steps towards strengthening diagnostics regulation, including Tanzania who are receiving support through a project with the World Health Organisation. New guidelines are under consideration and are expected to result in some realignment of activities with the Tanzanian Food and Drug Authority assuming some duties currently under the remit of the Private Health Laboratories Board. Policies in Kenya are similarly under review with the aim to better define the respective roles of the Kenya Medical Laboratory Technicians and Technologist Board (KMLTTB) which has responsibility for the quality of medical laboratory activities and the Pharmacy and Poisons Board which regulates medicines.

Pre-market regulation
Whereas some regulatory activity was reported in each Partner State more detailed questioning revealed that with the exception of Tanzania pre market regulation of medical devices and IVDs by National Regulatory Authorities is largely absent across the EAC (Table 3).
No audit visits to manufactures to assess quality systems are currently undertaken by EAC Partner States. There is some scrutiny of products for the control of TB, malaria, HIV and other STIs and while some States accept products approved by donor agencies without further testing others choose to undertake pre market testing of IVDs in local laboratories. Some harmonization of regulatory processes was observed with cooperation between the Food and Drug Authorities of Tanzania mainland and Zanzibar with mutual recognition of some activities. Tanzania also reported that for products with prior regulatory approval from a stringent National Regulatory Authority (Canada, Japan, Australia, EU and USFDA) or prequalification by WHO could be reviewed using an abridged dossier.

Market and post market controls
In the absence of regulatory capacity for medical devices and IVDs market controls in EAC Partner States are not specific for these products. Three States, Burundi, Kenya and Tanzania require manufacturers to have a local agent with legal accreditation prior to registering a product for distribution in the country. Authorization for import is required in Tanzania and Uganda, with some enforcement in Tanzania through warehouse inspections.
Advertising controls were reported in Burundi, Tanzania and Uganda with some vetting and pre approval required. Post market regulation was reported as being reactive rather than proactive. Tanzania and Uganda reported that reactive investigations were undertaken if problems were reported. In Rwanda post market monitoring is undertaken by Programmes (HIV/AIDS, TB etc.). The Private Health Laboratories Board in Tanzania was the only organization that reported a mechanism for tracking medical devices or guidelines for recalling substandard medical devices or IVDs, although some other States reported mechanisms for reporting and recall of pharmaceuticals.

National capacity
Data supplied by Member States suggests that capacity to regulate either medical devices or diagnostic tests within the EAC is limited. Capacity is divided between persons with laboratory based technical expertise regarding the use of medical devices and persons with regulatory experience of pharmaceuticals but little or no knowledge of IVD or other medical devices. Regulation of some IVD that are considered high risk to individual or public health requires knowledge of their efficacy obtained from clinical trials to assess their performance in the target population. Little direct involvement of regulatory agencies in IVD clinical trials was reported but all countries reported some capacity for laboratory assessment of IVD. In addition Burundi, Kenya, Tanzania (mainland) and Uganda reported capacity for clinical trials for devices applicable to TB, HIV and malaria. Formalized Technology Assessment Programmes are absent in all EAC Partner States but both Uganda and Kenya have research institutions with some experience in technology assessment for IVD.
The quality of laboratory studies is critical for both pre market evaluation and post market surveillance and accreditation of laboratories is a highly desirable prerequisite. Respondents from Kenya and Uganda reported a number of laboratories accredited to international standards and Tanzania is currently engaged in a programme designed to lead to laboratory accreditation.

Conclusions
This study was undertaken to inform the EAC Secretariat and EAC Partner States of the current status of regulatory activities for medical devices and medical diagnostics within the EAC region. Data and opinions collected indicate that regulation of medical devices and in vitro diagnostics is a neglected area. Regulation is weak across the region, and although the majority of Member States have a legal mandate to regulate medical devices there is limited capacity to do so. Responses received suggest that harmonization and streamlining regulation in the EAC is seen as a positive aspiration. That rapid IVD to detect important infectious diseases are seen as a priority for harmonisation is not surprising in light of health needs in this region of Africa. However, a limitation of the study is that due to restraints of time and finance the list of stakeholders consulted was not exhaustive and it is possible that those who were not available for comment would be less enthusiastic about the regulation of IVD and medical devices. Several respondents indicated that policy reviews are being undertaken and at least one State (Tanzania) is proposing changes to the current regulatory framework and process. The collaboration between the NRAs in United Republic of Tanzania is fertile ground for regulatory harmonisation process in the region. Future activities planned include establishing a Task Force and Technical Working Groups to take forward strengthening and streamlining regulatory activities in the EAC and it is clear that investment shall be needed to increase capacity.