ArticlePDF AvailableLiterature Review

Optimizing the East African Community’s Medicines Regulatory Harmonization initiative in 2020–2022: A Roadmap for the Future

Authors:
  • Tanzania Medicines and Medical Devices Authority
  • Rwanda Food and Drugs Authority

Abstract and Figures

• The East African Community (EAC)’s Medicines Regulatory Harmonization (MRH) initiative was created to improve access to quality, safe medicines in the region by simplifying the regulatory process while maintaining a high level of rigor. Building on lessons learned since its launch in 2012, the EAC MRH initiative has created a Roadmap for the Future. • The capacity to monitor and reports adverse drug reactions is key for patients’ safety. Therefore, going forward, drug safety and quality surveillance will be a priority for the EAC MRH initiative. • In the future, other key success factors for the initiative will include establishing a cadre of regional technical officers (RTOs), a Cooperation Framework Agreement between the national medicines regulatory authorities (NMRAs) of EAC Partner States, and a sustainable funding mechanism for regional assessment. • Widening the scope of medical products considered (and focusing on those not eligible for the World Health Organization [WHO]’s Prequalification Programme) will also add value to the EAC MRH initiative. • Implementing the EAC MRH initiative’s agreed upon roadmap will lead to a stronger, more efficient, and more accountable region-wide regulatory system, thus improving access to quality, safe medicines for EAC residents. Copyright: © 2020 Arik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Content may be subject to copyright.
COLLECTION REVIEW
Optimizing the East African Community’s
Medicines Regulatory Harmonization initiative
in 2020–2022: A Roadmap for the Future
Mawien Arik
1
, Emmanuel Bamenyekanye
2
, Adam FimboID
3
, Joseph KabatendeID
4
, Agnes
Sitta KijoID
3
, Burhani SimaiID
5
, Fred SiyoiID
6
, Samvel Azatyan
7
, Aggrey Ambali
8
,
Emer CookeID
7
, Jane H. MashingiaID
9
, John Patrick Mwesigye
9
, Margareth Ndomondo-
SigondaID
8
*, Hiiti Sillo
7
, Stanley SonoiyaID
9
, Paul Tanui
8
, Mike Ward
7
, Thomas Delano
10
1Drug and Food Control Authority, Juba, South Sudan, 2Directorate of Pharmacy, Medicines, and
Laboratories, Bujumbura, Burundi, 3Tanzania Medicines and Medical Devices Authority, Dar Es Salaam,
Tanzania, 4Rwanda Food and Drugs Authority, Kigali, Rwanda, 5Zanzibar Food and Drug Agency,
Zanzibar City, Zanzibar, 6Pharmacy and Poisons Board, Nairobi, Kenya, 7World Health Organization,
Geneva, Switzerland, 8African Union Development Agency–New Partnership for Africa’s Development,
Midrand, South Africa, 9East African Community Secretariat, Arusha, Tanzania, 10 Boston Consulting
Group, Paris, France
*margarets@nepad.org
Summary Points
The East African Community (EAC)’s Medicines Regulatory Harmonization (MRH)
initiative was created to improve access to quality, safe medicines in the region by sim-
plifying the regulatory process while maintaining a high level of rigor. Building on les-
sons learned since its launch in 2012, the EAC MRH initiative has created a Roadmap
for the Future.
The capacity to monitor and reports adverse drug reactions is key for patients’ safety.
Therefore, going forward, drug safety and quality surveillance will be a priority for the
EAC MRH initiative.
In the future, other key success factors for the initiative will include establishing a cadre
of regional technical officers (RTOs), a Cooperation Framework Agreement between
the national medicines regulatory authorities (NMRAs) of EAC Partner States, and a
sustainable funding mechanism for regional assessment.
Widening the scope of medical products considered (and focusing on those not eligible
for the World Health Organization [WHO]’s Prequalification Programme) will also add
value to the EAC MRH initiative.
Implementing the EAC MRH initiative’s agreed upon roadmap will lead to a stronger,
more efficient, and more accountable region-wide regulatory system, thus improving
access to quality, safe medicines for EAC residents.
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OPEN ACCESS
Citation: Arik M, Bamenyekanye E, Fimbo A,
Kabatende J, Kijo AS, Simai B, et al. (2020)
Optimizing the East African Community’s
Medicines Regulatory Harmonization initiative in
2020–2022: A Roadmap for the Future. PLoS Med
17(8): e1003129. https://doi.org/10.1371/journal.
pmed.1003129
Published: August 12, 2020
Copyright: ©2020 Arik et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.
Funding: The development of the Roadmap and
preparation of the manuscript were supported by
the Bill & Melinda Gates Foundation.
Competing interests: I have read the journal’s
policy and the authors of this manuscript have the
following competing interests: the Bill & Melinda
Gates Foundation supported the preparation of the
article.
Abbreviations: AMA, African Medicines Agency;
AUDA-NEPAD, African Union Development
Agency–New Partnership for Africa’s Development;
AVAREF, African Vaccine Regulatory Forum; CRO,
contract research organization; EAC, East African
Community; FDA, United States Food and Drug
Administration; GMP, good manufacturing
Introduction
The combination of artesunate with amodiaquine is widely used to treat malaria in sub-Saha-
ran Africa. However, in 2012, a researcher noticed something concerning: 43 reports in adults
and 6 reports in children of acute extrapyramidal reactions associated with the use of this com-
bination [1]. These reports, collected by the World Health Organization (WHO)’s global Indi-
vidual Case Safety Report VigiBase database, hosted and managed by Sweden’s Uppsala
Monitoring Centre, along with data gathered by the manufacturer, resulted in a new labeling
and package insert for the medicine combination that warned of the potential for acute extra-
pyramidal reactions [2]. (Drug-induced extrapyramidal side effects are movement disorders
with acute and long-term symptoms, including dystonia, akathisia, parkinsonism, bradykine-
sia, tremor, and tardive dyskinesia.) Without the help of the eight sub-Saharan African coun-
tries that submitted reports to VigiBase, it is unclear whether the association between the
medicine combination and this adverse event would have been detected. Because of the coun-
tries’ vigilance, healthcare providers can now be alert for these reactions and treat them
promptly. Unfortunately, due to a number of factors, including inadequate legal framework
and infrastructure, limited financial resources, and the number and competency of staff avail-
able to support pharmacovigilance systems, many African countries struggle to gather and
report information about suspected adverse events, which is key for monitoring the safety of
medicines on the market. Today, fewer than 10% of reports to VigiBase come from low- and
middle-income countries, where roughly 84% of the world’s population resides [3,4]. Building
a more robust framework for post-marketing surveillance of the safety and quality of medi-
cines is a pressing need in African countries, one that will only become more urgent as a grow-
ing number of medicines used primarily by Africans emerges, thanks to the product
development partnerships and programs that are currently targeting diseases endemic in low-
and middle-income countries.
To ensure that its residents have access to safe, quality medicines, the East African Commu-
nity (EAC) is expanding its Medicines Regulatory Harmonization (MRH) initiative to include
a product safety and quality surveillance workstream, which will include reporting suspected
adverse reactions to medicine manufacturers and the WHO. Indeed, this is just one of many
areas in which the initiative plans to grow in the coming years. In this article, one of five in a
Special Collection about the EAC MRH initiative, we will describe the Roadmap for the Future
(“The Roadmap”) that the EAC MRH initiative has created for growing into a mature, stable
program capable of meeting more of the region’s regulatory needs by 2022 [5]. We believe that
sharing the EAC’s vision for the next phase of the MRH initiative and its plans for achieving
that vision may be helpful for other regions embarking on similar initiatives to harmonize reg-
ulatory standards, optimize regulatory processes, and increase regional collaboration.
Creating the Roadmap for the Future, 2020–2022
In 2017, as the end of the 5-year pilot phase of the EAC MRH initiative approached, the pro-
gram established a task force that worked with the Boston Consulting Group to determine the
initiative’s goals for the next 5 years and how those goals could be achieved. In particular, its
aim was to identify steps that could be taken (1) over the short term, to improve existing pro-
cesses and expand into new regulatory areas and activities; (2) in the period between 2020 and
2022, to develop a well-coordinated and well-functioning regional assessment and inspection
process, upon which national registration decisions will rely; and (3) over a longer period, to
create a sustainable, semiautonomous agency that will provide regulatory guidance and coor-
dination for the entire region by 2022. The task force created a roadmap detailing how the ini-
tiative could achieve each of these objectives and presented its plans to all EAC Partner States,
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practice; IMS, information management system;
IVD, in vitro diagnostic; MRH, Medicines
Regulatory Harmonization; NMRA, national
medicines regulatory authority; PAHWP, Pan
African Harmonisation Working Party on Medical
Devices and Diagnostics; PIC/S, Pharmaceutical
Inspection Cooperation Scheme; RTO, regional
technical officer; SOP, standard operating
procedure; Swissmedic, Swiss Agency for
Therapeutic Products; WHO, World Health
Organization.
Provenance: Not commissioned; externally peer-
reviewed.
as well as key initiative funding and technical partners, such as the African Union Develop-
ment Agency–New Partnership for Africa’s Development (AUDA-NEPAD), WHO, the Swiss
Agency for Therapeutic Products (Swissmedic), and the Bill & Melinda Gates Foundation.
After the task force integrated the stakeholder feedback it received, the EAC’s Council of
Health Ministers approved the Roadmap in 2018. Since then, the initiative has been carrying
out the actions prescribed in the document.
Major features of the Roadmap for the Future
Improving existing regulatory activities
In the EAC MRH initiative’s joint process for assessing marketing applications, staff from two
national medicines regulatory authorities (NMRAs) are assigned to perform a thorough initial
assessment of the product application. They then share their findings for wider discussion by
all the EAC’s NMRAs, which in turn decide whether to recommend approval of the product.
Ultimately, each NMRA makes its own decision regarding whether to register the product
nationally. However, the rigorous product review provided by the joint assessment is intended
to substantially reduce the amount of time needed for NMRAs to make their final decisions.
By participating in the joint assessment process, manufacturers should be able to more effi-
ciently receive marketing authorization in multiple EAC Partner States. Unfortunately, feed-
back from users of the initiative’s pilot program for joint product assessments has revealed
some challenges, including a lack of easily accessible public information about the process,
poor communication from regulators during the joint assessment process, and a significant
lag time between a joint assessment recommendation and national registration decisions [5,6].
Similar problems have been reported for the initiative’s good manufacturing practice (GMP)
joint inspection program.
To address these problems, the Roadmap (Fig 1) calls for a cadre of regional technical offi-
cers (RTOs) who are focused on the day-to-day management of joint activities. In the pilot
phase of the EAC MRH initiative, the EAC Secretariat hired one officer for each NMRA to
conduct program activities. However, these officers focused primarily on capacity-building
activities; often, they and other NMRA staff did not have the time to plan and conduct joint
activities efficiently. The RTOs—who will be selected and paid by their home NMRAs—will
work alongside the existing program officers and will concentrate solely on facilitating regional
regulatory activities (i.e., receiving and screening joint applications, planning joint activity ses-
sions in collaboration with the EAC Secretariat, and sharing application dossiers and joint
activity findings with other NMRAs). The RTOs will meet face to face at least once a quarter
and will use their expertise in joint activities to recommend programmatic changes to the ini-
tiative’s steering committee.
To ensure that all the program’s priorities are being championed, each NMRA now has one
RTO, each of whom specializes in a different area. Burundi’s RTO supports clinical trial over-
sight; Kenya’s, pharmacovigilance; Rwanda’s, information management systems (IMSs); South
Sudan’s, policy, legal, and regulatory reforms; Tanzania’s, joint product assessments; Uganda’s,
joint GMP inspections; and Zanzibar’s, quality management systems. In April 2019, the EAC
Secretariat organized the RTOs’ first meeting, where the officers reviewed the initiative’s prog-
ress; developed advocacy and communication materials to increase the visibility of the initia-
tive [7]; and created tools that the NMRAs can use to track joint activity timelines, to increase
transparency. The RTOs now provide the single point of contact for joint activities. For exam-
ple, for a joint product assessment, Tanzania’s RTO will now distribute dossiers to each EAC
NMRA, so the applicant does not have to do it themselves. The RTO will also screen the dos-
sier to ensure that all major issues are raised before the joint assessment takes place and work
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with the EAC Secretariat to plan joint assessments at a time convenient for all parties involved,
including technical partners such as Swissmedic or WHO. Finally, once a product has been
recommended through the joint assessment process, the RTO will follow up with NMRAs to
ensure that national registrations proceed in a timely manner.
The Roadmap also calls for establishing a Cooperation Framework Agreement among the
EAC’s Partner States, so that a joint assessment or inspection decision will be honored
throughout the region. In May of 2018, the EAC’s Council of Health Ministers approved a
Cooperation Framework Agreement for the NMRAs of EAC Partner States [8]. In this docu-
ment, EAC Partner States agreed to make regulatory decisions in a timely manner based on
the outcomes of the initiative’s joint activities; however, final regulatory decisions will remain
with individual NMRAs. As an intermediary step toward a binding mutual recognition agree-
ment between all Partner States, the initiative will pursue unilateral recognition agreements,
like the one in which Zanzibar’s NMRA agrees to recognize the regulatory decisions of Tanza-
nia’s NMRA, as well as bilateral agreements. By 2022, the program aims to have at least three
one-to-one recognition agreements in place, as well as a draft of a binding region-wide mutual
recognition agreement.
Ultimately, it is envisioned that a coordination fee will be introduced to support regional
assessment and inspection processes. Applicants seeking marketing authorization in the EAC
could submit a single application and pay a single fee to register their products in every Partner
State (Fig 2). The proposed funding scheme would be similar to the one used for the EAC Sin-
gle Tourist Visa, whereby visitors to Kenya, Rwanda, and Uganda pay a single application fee
of $100 at their point of entry. This master fee includes a $10 administration fee for the country
Fig 1. The Roadmap for the Future of the EAC’s MRH initiative, 2020–2022. CRO, contract research organization; EAC, East African Community;
GMP, good manufacturing practice; ISO, International Organization for Standardization; IVD, in vitro diagnostic; JA, joint assessment; MRH,
Medicines Regulatory Harmonization; NMRA, national medicines regulatory authority; PV, pharmacovigilance; RTO, regional technical officer; WHO,
World Health Organization.
https://doi.org/10.1371/journal.pmed.1003129.g001
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that collects the funds and $30 for each of the three countries involved. The simplicity and effi-
ciency of this arrangement would be extremely appealing to pharmaceutical companies.
One of the Roadmap’s long-term goals is to establish a semiautonomous EAC Medicines
Agency that is devoted to conducting joint activities. With dedicated staff including an execu-
tive director, a joint activity coordinator, a working group coordinator, and an accountant, an
EAC Medicines Agency could raise the visibility of the initiative across the region and ensure
that the program continues to grow and improve. It would assume responsibility for coordi-
nating joint activities from the EAC Secretariat, which would increase efficiency and conve-
nience for all parties involved. It could also continue to promote a legal framework for reliance
on and recognition of joint assessment recommendations, as well as other regulatory work
products and decisions, by EAC Partner States. This could allow a user to submit a single
application for marketing authorization or GMP certification throughout the EAC. By 2022,
the initiative aims to have obtained legal authority for the agency through adoption of a proto-
col by the EAC Council of Ministers.
Expanding to new Partner States, medical products, and regulatory
activities
In 2016, the EAC welcomed its newest Partner State: South Sudan. The Roadmap includes
plans to fully integrate this new member into the EAC MRH initiative in 2020. South Sudan’s
NMRA has been working with Tanzania’s NMRA to quickly build an effective regulatory sys-
tem, even amidst challenging domestic realities. The Roadmap contains a comprehensive plan,
discussed in detail below, for building the capacity of South Sudan’s new NMRA, as well as the
new NMRAs of Rwanda and Zanzibar and the soon-to-be new NMRA of Burundi.
In addition, the Roadmap calls for the initiative’s scope to widen to include new types of
medical products, such as in vitro diagnostics (IVDs), vaccines, biologics and biosimilars, and
Fig 2. A model for how the EAC’s MRH initiative could finance regional regulatory activities. In this example, an applicant seeking to market their
product in the EAC would pay a single fee to a regional coordination desk, which would then divide the money between each Partner State, setting
aside a coordination fee for shepherding a single application through the regional product assessment process. A similar model could be used for GMP
inspections. These fees are only illustrative and the models are not yet in use, but they are expected to be in place by 2022. EAC, East African
Community; FAQs, frequently asked questions; GMP, good manufacturing practice; MRH, Medicines Regulatory Harmonization.
https://doi.org/10.1371/journal.pmed.1003129.g002
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medical devices. (Biologics are products made from living organisms or that contain compo-
nents of living organisms, whereas biosimilars are officially approved versions of original
"innovator" biological products, produced according to the same standards of pharmaceutical
quality, safety, and efficacy; a biosimilar can be manufactured when the original product’s pat-
ent expires.) For maximum efficiency, the program will concentrate on medical products that
are not eligible for the WHO’s Prequalification Programme [9]. The WHO Prequalification
Programme was primarily set up to evaluate and recommend products that meet WHO stan-
dards of quality and efficacy to UN procurement agencies and other global health product pro-
curers (e.g., the Global Fund, UNICEF, GAVI). The WHO’s Prequalification Programme for
IVDs, for example, prioritizes tests for HIV, hepatitis B and C, malaria, human papillomavirus,
cholera, and syphilis [10]. Many emerging IVDs that could potentially be useful in the EAC,
such as culture-independent assays to rapidly detect sepsis and analyze the antibiotic suscepti-
bility of the organisms responsible [11] and rapid antibody tests for loiasis, a skin and eye
disease caused by a parasitic worm [12], are not currently eligible for the Prequalification Pro-
gramme—and access to IVDs such as these could be improved by the presence of a robust
regional regulatory framework. By the end of 2020, the initiative aims to define guidelines for
assessing novel IVDs and to include IVDs within the scope of its joint assessments; by 2022, it
aims to have performed joint assessments of at least 10 IVD products.
The initiative will also expand into regulating vaccines that are not eligible for the WHO’s
Prequalification Programme [13]. The shingles vaccine, for example, is not listed on the
WHO’s priority list for its Prequalification Programme, but access to it could improve quality
of life for many of the EAC’s older citizens. Thus, the ability to assess joint marketing applica-
tions for this and other vaccines is an important step in building the EAC’s regulatory capacity.
In August 2019, the initiative finalized guidelines for assessing novel vaccines. By early 2020,
the program will include vaccines within the scope of its joint assessments, and by 2022, it
aims to have performed joint assessments of at least 10 vaccines.
Expanding into the assessment of biologics and biosimilars is also important for ensuring
that EAC residents have access to the newest and most effective medicines. The WHO recently
launched a new Prequalification Programme for biotherapeutics, but it is currently only
accepting applications for two agents (and their biosimilars): rituximab, used principally to
treat hematologic malignancies, and trastuzumab, used principally to treat breast cancer [14].
The EAC has the opportunity to improve access to other biologics and biosimilars, which are
used to treat conditions as diverse as arthritis, psoriasis, multiple sclerosis, and diabetes, by
beginning to assess these types of products. By 2022, the initiative aims to finalize and imple-
ment guidelines for assessing novel biologics and biosimilars. Because assessing applications
for biologics and biosimilars requires special expertise, all applications for these products will
be routed to joint assessments, in which two NMRAs can combine their expertise and skills
with those of technical partners to produce a robust assessment that all the EAC’s NMRAs can
use to make national registration decisions.
Finally, the initiative will expand into regulating medical devices. The WHO’s Prequalifica-
tion Programme currently covers very few devices (e.g., immunization devices, male circumci-
sion equipment) [15,16]. However, many other medical devices, such as pacemakers and
infusion pumps, would be helpful to the people of the EAC, and the initiative can improve
access to such devices through a joint assessment program. To this end, the initiative aims to
adopt guidelines for assessing medical devices by 2022.
Tanzania’s NMRA will spearhead expansion into these new product areas. It currently
leads the Medicines Evaluation and Registration Working Group, which will now encompass
the registration of vaccines and biologics/biosimilars as well. Going forward, it will also lead
one working group on IVD registration and one on medical device registration. In developing
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guidelines for IVDs and medical devices, these working groups will benefit from the progress
made by the Pan African Harmonisation Working Party on Medical Devices and Diagnostics
(PAHWP). The founding members of PAHWP, which is housed under AUDA-NEPAD,
include the EAC’s Health Secretariat and Partner States, as well as Ethiopia, Nigeria, South
Africa, and the London School of Hygiene & Tropical Medicine. With the help of partners
such as the German Agency for International Cooperation, African Society for Laboratory
Medicine, and WHO, PAHWP has been developing a common registration file to use for
IVDs and medical devices, harmonizing rules for assigning a level of regulatory control that
matches the risk these products pose to public health, and harmonizing guidelines for assess-
ing these products and auditing the quality systems of product manufacturers [17]. Again, the
initiative’s expansion in this area would encompass products not eligible for assessment by the
WHO Prequalification Programme.
The last area in which the Roadmap calls for the initiative to expand is in the scope of its
regulatory activities. The original vision was for the EAC MRH initiative to extend from pre-
marketing activities, such as overseeing clinical trials, through product marketing application
assessments and GMP inspections, to post-marketing safety and quality surveillance. By 2022,
the initiative plans to realize this vision.
The need for effective, efficient clinical trial oversight in the EAC is pressing; in particular,
the region needs a harmonized, transparent system with common requirements and standards.
Without such a system, trial sponsors struggle to meet disparate requirements in different
countries, making the region unattractive for trials. Trial sponsors often cite regulatory diffi-
culties as a major reason for not undertaking trials across Africa. If one wants to undertake a
trial, the regulatory guidelines are not readily available and differ from country to country in
significant ways. Anyone seeking to carry out trials must spend valuable time understanding
these different requirements and standards, and must submit different protocols in different
countries for multicountry trials. When this barrier is added to other barriers, it makes Africa
unattractive to trial sponsors. This is not a good state of affairs, as it means therapies get
licensed without taking into account the unique genetic makeup of Africans or the environ-
ments and healthcare systems in which they live. These issues impact the appropriate dosing
for a drug as well as its adverse event profile, yet important evidence on these topics emerges
only after a product has been in use for several years in Africa, placing African patients at a dis-
advantage. As of June 2019, 332 clinical trials were registered in the EAC, 42 of them (13%) in
multiple EAC Partner States [18]. The African Vaccine Regulatory Forum (AVAREF), which
recently played a key role in expediting clinical trials of candidate Ebola vaccines and medical
therapies [19], has already developed guidelines for the oversight of multiregional clinical trials
in Africa [20]. These guidelines, along with the new Multi-Regional Clinical Trial guidelines
released by the International Council for Harmonisation of Technical Requirements for Phar-
maceuticals for Human Use [21], form a strong basis for the regional assessment of proposed
clinical trials in Africa. The EAC plans to adapt these guidelines, using them to set minimum
requirements for the oversight of any clinical trial that is conducted within its borders. To do
so, it will rely on the expertise of a working group on clinical trials led by Burundi. By the end
of 2020, the initiative plans to finish adapting the AVAREF guidelines, begin conducting joint
evaluations of trials that span multiple EAC Partner States, develop guidelines for inspecting
the contract research organizations (CROs) that conduct clinical trials, and begin conducting
joint inspections of CROs.
The initiative will also expand its pharmacovigilance work, to better ensure access to safe
and effective medicines. In March of 2019, the EAC Sectoral Council of Ministers approved
the EAC Harmonized Compendium of Guidelines for Pharmacovigilance [22]. These harmo-
nized guidelines were created by a working group on pharmacovigilance led by Kenya’s
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NMRA and include procedures and policy tools for reporting and sharing information on
potential adverse reactions associated with registered medicines. In addition, Kenya, Tanzania,
and Uganda are official members of the WHO Programme for International Drug Monitoring.
They regularly send case reports of suspected adverse reactions to VigiBase, where the reports
can be analyzed alongside those from other sources to determine whether countries should be
alerted of potential safety signals. We expect that the addition of pharmacovigilance activities
to the EAC MRH initiative will increase the number of EAC countries reporting adverse events
to VigiBase, as well as the overall number of reports.
The initiative is also committed to increasing its laboratory field surveillance activities in
order to help assure the quality of medicines on the market in EAC countries. Of note, Kenya,
Tanzania, and Uganda are three of only five countries in sub-Saharan Africa with WHO-pre-
qualified laboratories for medicine quality testing [23]. Moreover, all EAC partner states except
for South Sudan have reported information to the WHO Global Surveillance and Monitoring
System for Substandard and Falsified Medical Products, to identify and alert others about the
presence of substandard and falsified products on the global market [24]. A program working
group devoted to post-marketing quality surveillance, also led by Kenya, is currently develop-
ing a harmonized protocol for joint lab testing of field samples of medicines. Recently, with
funding from Physikalisch-Technische Bundesanstalt, the EAC MRH initiative completed a
study of the quality of antibiotics circulating in EAC Partner States, analyzing a little over 200
samples [25]; the findings resulted in the recall of one batch of drugs, and the knowledge
gained will provide a foundation for further quality-surveillance activities in the EAC.
Enhancing existing regulatory activities and building capacity
While beginning to assess new products and initiating new regulatory activities, the program
will also strengthen and further optimize the activities it has performed from the start. Numer-
ous improvements are planned for joint product assessments and GMP inspections. For exam-
ple, in line with the Roadmap, in 2019 the initiative developed standard operating procedures
(SOPs) for the joint processing of product variations and renewals, in response to a frequent
request from medicine manufacturers active in the EAC. In addition to satisfying user
demand, the ability to process product renewals more efficiently will help ensure that products
on the EAC market retain their quality and are appropriately labeled. The initiative hopes that
with these improvements and the enthusiasm and dedication of the program’s RTOs, by 2022
joint activities will become part of the everyday work of each NMRA, and that the number of
joint assessments and GMP inspections will grow every year.
NMRA capacity building will also continue to be a major focus. The initiative will continue
to design an IMS that connects all seven of the EAC’s NMRAs. This will entail setting up an
IMS in South Sudan, as well as extending the regional IMS to handle payment, post-marketing
surveillance, and clinical trial data. In terms of quality management, the initiative aims to have
Rwanda, Burundi, and South Sudan achieve ISO 9001:2015 certification by 2022 so that all
Partner States are on an even ISO level. Several Partner State NMRAs will also seek to receive
Pharmaceutical Inspection Cooperation Scheme (PIC/S) or WHO certification for their GMP
inspection programs by 2022. All NMRAs except for that of South Sudan will undergo formal
WHO Global Benchmarking Tool assessments by 2022 as well, with the goal of each NMRA
reaching a maturity level of 3 or higher. (According to the WHO’s Global Benchmarking Tool,
Maturity Level 1 implies that there are some elements of a regulatory system existing in an
agency; Maturity Level 2 means there is an evolving national regulatory system that partially
performs essential regulatory functions; Maturity Level 3 indicates a stable, well-functioning,
and integrated regulatory system; and Maturity Level 4 describes a regulatory system that is
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operating at an advanced level of performance and continuous improvement [26].) Tanzania’s
NMRA recently became the first in Africa to attain this maturity level. Finally, the program
will work with partners such as the WHO and well-resourced regulatory authorities outside of
the EAC, such as the European Medicines Agency, to continue developing its staff’s expertise
in regulatory affairs, and it will also develop a partnership with at least one university outside
of the EAC that has a strong regulatory science curriculum.
Creating the financial infrastructure to sustain the initiative
To date, the EAC MRH initiative has been financed primarily through donor funds (private
foundations and bilateral and multilateral organizations). To ensure that the program can sus-
tain its current work and the growth it has planned, it must transition to a system in which it
becomes self-sustaining. The funding required is relatively modest. The Boston Consulting
Group has estimated that it will cost approximately US$500,000 per year to maintain the initia-
tive in its current state and roughly US$1.8 to US$2.6 million per year to set up and run the
EAC Medicines Agency [5]. However, securing adequate funding is viewed by many of the ini-
tiative’s stakeholders as the most challenging part of its transition from a pilot program to a
durable institution. Currently, the initiative plans to support itself with a mixture of applica-
tion fees and contributions from Partner States’ NMRAs, although additional donor funding
may be required to establish the EAC Medicines Agency.
Industry representatives have expressed eagerness to pay higher fees for product registra-
tion applications in order to fund a system that is robust, predictable, accountable, and trans-
parent, with a single point of contact. This suggests that once an optimized process for
regional product assessments and GMP inspections is fully operational, the initiative could
support itself by levying regional coordination fees for joint activities (Fig 2). One analysis esti-
mated that 60 regional applications a year could potentially support an RTO-led coordination
desk for regional assessments and inspections, and 145 regional applications a year could sup-
port an EAC Medicines Agency [5]. Thus, it seems reasonable that as the frequency of joint
activities grows, the initiative can eventually support itself without donor funding, just as some
of the EAC’s more mature NMRAs are already supporting themselves almost solely through
the fees they take in [27]. By the end of 2021, the initiative aims to have implemented this new
revenue model financed primarily by regional activities. Industry paying fees for service to reg-
ulators is a global standard used by a majority of regulatory agencies, including the United
States Food and Drug Administration (FDA), the European Medicines Agency, and all regula-
tory agencies in East Africa. These fees are generally linked to a client charter, which sets
expectations in terms of the services to be provided and key performance indicators. The fees
for marketing authorization, for example, cover the service of assessing an application and pro-
viding a decision (accept or reject); the fee has nothing to do with the outcome of the review.
Conclusion
The EAC MRH initiative’s Roadmap describes many paths to a stronger, more efficient, and
more accountable region-wide regulatory system. Although some changes, such as establishing
an EAC Medicines Agency, will take years, numerous critical changes will take place in the
next year or two. These key improvements will include the following:
More robust and predictable joint product assessments and GMP inspections, which will
result in more efficient national registrations
The improved capacity of all NMRAs to engage in critical regulatory activities
Increased revenue driven by an increase in joint activities
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PLOS Medicine | https://doi.org/10.1371/journal.pmed.1003129 August 12, 2020 9 / 11
Both the short- and long-term improvements planned during the next phase of the initia-
tive will have an immediate impact on the ability of EAC residents to access quality, safe medi-
cines. These improvements will also help pave the way for establishing a continent-wide
initiative to harmonize technical regulatory standards for medicines and to optimize regula-
tory processes, in the form of the African Medicines Agency (AMA), whose treaty was
endorsed by the heads of government of the African Union in 2019 and is expected to be rati-
fied in the next 2 to 3 years. Although we recognize that the EAC MRH initiative’s plans for
the future may seem ambitious, we believe they are feasible, given the program’s accomplish-
ments during its pilot phase. We look forward to reporting the program’s progress in future
publications, and we hope to hear from regulatory experts in other regions of the world who
are interested in sharing ideas about how to improve regional approaches to delivering more
robust, efficient, predictable, accountable, and sustainable regulatory activities.
Acknowledgments
The authors thank Kristin Harper, PhD, of Harper Health & Science Communications, for
providing writing and editorial support in accordance with Good Publication Practice (GPP3)
guidelines. They also thank the Boston Consulting Group for its help in developing the
Roadmap.
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... This approach facilitates specialisation, ensures that all member states actively participate in the initiative and leverage the region's limited expertise [10,46]. The EAC MRH initiative is now implementing its "Roadmap for the Future, 2020-2022," which was approved in 2018 by the EAC's Council of Health Ministers [49]. The Roadmap calls for the appointment of regional technical officers (RTOs) who concentrate solely on the day-to-day management of joint regulatory activities as well as recommend programmatic changes to the EAC MRH initiative's Steering Committee [49]. ...
... The EAC MRH initiative is now implementing its "Roadmap for the Future, 2020-2022," which was approved in 2018 by the EAC's Council of Health Ministers [49]. The Roadmap calls for the appointment of regional technical officers (RTOs) who concentrate solely on the day-to-day management of joint regulatory activities as well as recommend programmatic changes to the EAC MRH initiative's Steering Committee [49]. Therefore, each NRA in the region now has an RTO that specialises in a different regulatory domain and serves as the contact point for joint activities. ...
... Therefore, each NRA in the region now has an RTO that specialises in a different regulatory domain and serves as the contact point for joint activities. Burundi's RTO supports the oversight of clinical trials; Kenya, pharmacovigilance; Rwanda, information management systems; South Sudan, policy, legal, and regulatory reforms; Tanzania, joint product assessments; Uganda, joint GMP inspections; and Zanzibar, quality management systems [49]. ...
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... However, a study on Medicines Regulation in Africa has shown that most NMRAs in Africa have little capacity to perform all key regulatory functions [9]. In East African Community, SF medicines have been reported in all member states [10]. ...
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... This includes a coordination fee to support regional assessment and inspection processes to complement donor funding. The long-term goal is to establish a semiautonomous EAC Medicines Agency which will ensure that the program continues to grow and improve [44]. ...
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... Previous evaluations of regulatory work have been published. 8,[14][15][16][17] We provide an updated review with a focus on medical device regulation in the 14 member countries of the College of Surgeons of East, Central, and Southern Africa (COSECSA). 18 COSECSA is the largest surgical training institution in sub-Saharan Africa, with a diverse international surgical membership who commonly use a wide range of medical devices. ...
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Acute extrapyramidal reactions have been attributed to amodiaquine. They may be anticipated with the widely-used combination antimalarial artesunate with amodiaquine, but the association is very poorly documented. The aim of the study was to identify individual case safety reports in the Uppsala Monitoring Centre's Vigibase™ database associating the use of the combination of artesunate and amodiaquine with extrapyramidal adverse reactions and to characterize the clinical features in those reports. Reports of adverse reactions to the combination use of artesunate or dihydroartemisinin and amodiaquine entered into Vigibase™ up to 15 February 2011 were identified. Reports with a causality grading of 'Unlikely' and probable duplicates of reports were excluded. Reports that included at least one MedDRA® Preferred Term strongly suggestive of an extrapyramidal reaction were subject to further detailed analysis. Forty-three reports in adults and six reports in children were identified as associating the use of artesunate with amodiaquine, either as separate co-packaged or fixed-combination products, with extrapyramidal reactions. More than half (57%) of the adults had an onset of the reaction within 48 hours of starting treatment. Almost equal numbers of male and female adult patients were reported - 67% were aged between 14 and 30 years. The most commonly implicated daily dose was amodiaquine base 600 mg and artesunate 200 mg, but lower doses were implicated in some adult patients. Identification of very long delays in some reports reaching Vigibase™ was an unexpected observation. This case series supports an association of the use of artesunate and amodiaquine as combination antimalarial therapy with acute extrapyramidal reactions. The reactions occurred with recommended, and in some instances reduced, daily doses. Extrapyramidal reactions are unpleasant and frightening and the association warrants being more clearly recorded in official treatment guidelines and Summary of Product Characteristics documents.