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Evaluation of the Good Review Practices of Countries Participating in the Southern African Development Community: Alignment and Strategies for Moving Forward

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Introduction: National medicines regulatory agencies are faced with challenges including limited resources and technical capacity, resulting in countries collaborating and sharing resources to improve efficiency of the review process to facilitate access to quality-assured medicines by their populations. One such collaboration is the Southern African Development Community (SADC) medicines registration collaborative initiative, ZaZiBoNa. Countries participate in the initiative by contributing to regulatory reviews and good manufacturing practices inspections. The aim of this study was to review and compare the registration processes of regulatory authorities of Mozambique, Namibia, South Africa, Tanzania, Zambia, and Zimbabwe to identify strategies for better alignment. Methods: A senior member of the division responsible for issuing marketing authorisations completed an established and validated questionnaire, which standardises the review process, allowing key milestones, activities and practices of the six regulatory authorities to be identified and compared. The completed questionnaires were validated by the heads of the respective agencies. Results: The six countries vary in population and in the size of their respective regulatory agency and the resources allocated to regulatory reviews. The review processes of the six agencies were similar; however, differences were noted in the milestones recorded; for example, two of the countries did not record the start of the scientific assessment. Additionally, decisions for marketing authorisation were made by an expert committee in four of the countries and by the head of the agency and the Minister of Health in two countries. All six agencies implemented the majority of good review practices; however, the need for improvement in the areas of transparency and communication and quality decision making practices was a common finding for all six countries. Conclusions: Participation in the ZaZiBoNa initiative has improved the way in which the six agencies perform regulatory reviews in their countries, highlighting the realisation of one of the key objectives of the initiative, which was building the expert capacity of member countries. Other agencies in the SADC region and beyond can use the results of this study to identify best practices, which in turn, could improve their regulatory performance.
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ORIGINAL RESEARCH
published: 27 August 2021
doi: 10.3389/fmed.2021.742181
Frontiers in Medicine | www.frontiersin.org 1August 2021 | Volume 8 | Article 742181
Edited by:
Steffen Thirstrup,
NDA Advisory Services Ltd,
United Kingdom
Reviewed by:
Birka Martha Luise Lehmann,
University of Bonn, Germany
Frits Lekkerkerker,
Consultant, Amsterdam, Netherlands
*Correspondence:
Stuart Walker
swalker@clarivate.com
Specialty section:
This article was submitted to
Regulatory Science,
a section of the journal
Frontiers in Medicine
Received: 15 July 2021
Accepted: 06 August 2021
Published: 27 August 2021
Citation:
Sithole T, Mahlangu G, Capote V,
Sitoie T, Shifotoka S, Gaeseb J,
Padayachee S, Sehloho T, Khea A,
Fimbo A, Munkombwe Z, Mwale B,
Salek S and Walker S (2021)
Evaluation of the Good Review
Practices of Countries Participating in
the Southern African Development
Community: Alignment and Strategies
for Moving Forward.
Front. Med. 8:742181.
doi: 10.3389/fmed.2021.742181
Evaluation of the Good Review
Practices of Countries Participating
in the Southern African Development
Community: Alignment and
Strategies for Moving Forward
Tariro Sithole 1,2 , Gugu Mahlangu 2, Velma Capote 3, Tania Sitoie 3, Saren Shifotoka 4,
Johannes Gaeseb 4, Silverani Padayachee 5, Tohlang Sehloho 5, Akida Khea 6,
Adam Fimbo 6, Zuma Munkombwe 7, Bernice Mwale 7, Sam Salek 1,8 and Stuart Walker 1, 9
*
1School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom, 2Medicines Control Authority of
Zimbabwe, Harare, Zimbabwe, 3National Directorate of Pharmacy, Mozambique Ministry of Health, Maputo, Mozambique,
4Namibia Medicines Regulatory Council, Namibia Ministry of Health and Social Services, Windhoek, Namibia, 5South African
Health Products Regulatory Authority, Pretoria, South Africa, 6Tanzania Medicines and Medical Devices Authority, Dodoma,
Tanzania, 7Zambia Medicines Regulatory Authority, Lusaka, Zambia, 8Institute for Medicines Development, Cardiff,
United Kingdom, 9Centre for Innovation in Regulatory Science, London, United Kingdom
Introduction: National medicines regulatory agencies are faced with challenges
including limited resources and technical capacity, resulting in countries collaborating
and sharing resources to improve efficiency of the review process to facilitate access to
quality-assured medicines by their populations. One such collaboration is the Southern
African Development Community (SADC) medicines registration collaborative initiative,
ZaZiBoNa. Countries participate in the initiative by contributing to regulatory reviews
and good manufacturing practices inspections. The aim of this study was to review and
compare the registration processes of regulatory authorities of Mozambique, Namibia,
South Africa, Tanzania, Zambia, and Zimbabwe to identify strategies for better alignment.
Methods: A senior member of the division responsible for issuing marketing
authorisations completed an established and validated questionnaire, which
standardises the review process, allowing key milestones, activities and practices
of the six regulatory authorities to be identified and compared. The completed
questionnaires were validated by the heads of the respective agencies.
Results: The six countries vary in population and in the size of their respective regulatory
agency and the resources allocated to regulatory reviews. The review processes of the
six agencies were similar; however, differences were noted in the milestones recorded;
for example, two of the countries did not record the start of the scientific assessment.
Additionally, decisions for marketing authorisation were made by an expert committee
in four of the countries and by the head of the agency and the Minister of Health
in two countries. All six agencies implemented the majority of good review practices;
however, the need for improvement in the areas of transparency and communication
and quality decision making practices was a common finding for all six countries.
Sithole et al. SADC Good Review Practices
Conclusions: Participation in the ZaZiBoNa initiative has improved the way in which
the six agencies perform regulatory reviews in their countries, highlighting the realisation
of one of the key objectives of the initiative, which was building the expert capacity
of member countries. Other agencies in the SADC region and beyond can use the
results of this study to identify best practices, which in turn, could improve their
regulatory performance.
Keywords: South African Development Community, ZaZiBoNa, regulatory reliance, good review practices,
constrained resources
INTRODUCTION
The Southern African Development Community (SADC) is
made up of 16 countries; Angola, Botswana, Comoros Islands,
Democratic Republic of Congo, Lesotho, Madagascar, Malawi,
Mauritius, Mozambique, Namibia, Seychelles, South Africa,
Swaziland, United Republic of Tanzania, Zambia, and Zimbabwe
(1). Although the countries have differing capacities to regulate
medicines (2), they share the common challenge of inadequate
capacity to review applications for medicines, resulting in
backlogs and delayed access to medicines by patients. This
led to the formation of a collaborative medicines registration
initiative called ZaZiBoNa by four countries, Zambia, Zimbabwe,
Botswana, and Namibia with technical support from the World
Health Organization (WHO) Prequalification team in 2013 (3).
The initiative was formally endorsed by the SADC Ministers of
Health in 2015, and member states who signed the memorandum
of agreement to participate in the initiative were assigned
active or non-active status, depending on their capacity to
conduct assessments and good manufacturing practices (GMP)
inspections. The remaining countries, Mauritius and Lesotho,
participate as observers (3).
Operational Aspects of ZaZiBoNa
ZaZiBoNa is a SADC work-sharing initiative, in which regulatory
authorities conduct joint or shared reviews of applications for
registration of medicines submitted to participating countries
with the applicant’s consent (3). One of the successes of
the ZaZiBoNa initiative is that since its inception in 2013,
more than 300 products have been reviewed and the median
time to a recommendation was shorter than that achieved by
individual participating countries using the national procedure
(4). However, because the ZaZiBoNa initiative is not a legally
constituted regulatory authority, it relies significantly on the
participating countries to achieve a number of key milestones
in the review process, particularly those of an administrative
nature (Figure 1) (3). As a result, one of the challenges that has
been identified with this initiative is the fact that differences
in country review processes result in questions to applicants
for the same product being sent at different times by the
countries, affecting registration timelines and negating the
benefit of simultaneous access to various markets. Sithole et al.
therefore recommended that the regulatory review processes
in the individual participating countries be reviewed and the
outcomes compared (3,5). The aim of this study therefore was
to review and compare the registration processes of regulatory
authorities of Mozambique, Namibia, South Africa, Tanzania,
Zambia, and Zimbabwe to develop recommendations for better
alignment, while presenting an opportunity for the countries
to learn from each other and enhance their regulatory review
and patients’ access to life-saving medicines. This article, the
first in a two-part series, details the findings, focusing on the
review processes and good review practices. The second article
will address review models and metrics of process.
MATERIALS AND METHODS
Study Participants
Nine countries with active member status in the ZaZiBoNa
initiative were invited to participate in the study following a face-
to-face presentation. Active member status is defined as “the
capacity to conduct assessments and GMP inspections.” One of
the countries (Botswana) could not complete the questionnaire
because their agency had only recently been established and
the lack of participation by two countries (the Democratic
Republic of Congo and Malawi) was likely because of disruptions
caused by the Covid-19 pandemic. Therefore, the six regulatory
agencies included in this study were the National Directorate
of Pharmacy in the Mozambique Ministry of Health; Namibia
Medicines Regulatory Council (NMRC) in the Namibia Ministry
of Health and Social Services; the South African Health Products
Regulatory Authority (SAHPRA); the Tanzania Medicines and
Medical Devices Authority (TMDA); the Zambian Medicines
Regulatory Authority (ZAMRA); and the Medicines Control
Authority of Zimbabwe (MCAZ).
Data Collection
Each of the six agencies completed an established and validated
questionnaire (6) in 2020, which described the organisational
structure, the regulatory review system for market authorisation
for new active substances (NASs) and generics as well as their
overall review times from the date of application to the date of
approval, good review practices (GrevP) and quality decision-
making practices. The questionnaire allowed for the collection of
data in a standardised format, enabling comparison and analyses
of information collected from the six agencies.
The questionnaire consists of five parts: Part 1, documents
the structure, organisation and resources of the agency; Part 2,
identifies different types of review model (s) used for the scientific
assessment of medicines; Part 3, documents information on the
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Sithole et al. SADC Good Review Practices
key milestone dates and the process using a standardised process
map; Part 4, records how quality is built into the regulatory
process (GrevP), and Part 5, explores the quality of the decision-
making practices of the agency.
Ethics Committee Approval
The study was approved by the Health, Science,
Engineering and Technology ECDA, University of
Hertfordshire, United Kingdom [Reference Protocol
number: LMS/PGR/UH/04350].
RESULTS
For the purpose of clarity, the results of this article (first of a series
of two) will be presented in four parts: Part I – organisation of
the regulatory authorities; Part II – key milestones in the review
process; Part III – good review practices; and Part IV – quality
decision-making practices. The second article of the series will
address the remaining results of the questionnaire.
Part I - Organisation of the Regulatory
Authorities
The six countries, Mozambique, Namibia, South Africa,
Tanzania, Zambia, and Zimbabwe, vary in population and size
of their respective regulatory agency (Table 1). South Africa
(58.8 million) and Tanzania (58.6) have the largest populations,
while Namibia has the smallest (2.6). Four countries, South
Africa, Tanzania, Zambia, and Zimbabwe have autonomous
agencies independent of the Ministry responsible for Health. All
six agencies have the common mandate to regulate medicinal
products, medical devices and in vitro diagnostics for human
and veterinary use, except for Mozambique, which does not
regulate products for veterinary use. In addition, the South
African agency also has the mandate to control the development
and use of radiation procedures (for medical use).
The ratio of total staff per million residents varied across
the six countries, with Namibia having the highest ratio of 10,
followed by Zimbabwe at 8.8, Zambia at 6.9, South Africa at
2.9, Mozambique at 2.8, and Tanzania at 1.8. The professional
background of the agency reviewers was primarily pharmacy for
all six agencies and only South Arica and Tanzania had physicians
as part of their review teams. Tanzania had the highest proportion
of reviewers to total agency staff (44%), followed by South Africa
(34%), Zambia (16%), Namibia (15%), Zimbabwe (13%), and
Mozambique (6%). The agencies in South Africa, Tanzania and
Zambia made use of external experts in the review of applications
for registration, employing at the time of the study, 32, 36, and
8 external reviewers, respectively, while the other countries used
only internal experts. Zimbabwe, however, had a provision for
use of external experts even though none were employed at the
time of the study.
If, hypothetically, all new applications received in a year were
reviewed in that same year, then the workload; that is, the number
of dossiers to be reviewed per year per internal reviewer for 2019
was the highest for Mozambique (42), followed by Namibia (37),
Zambia (31), Tanzania (19), and Zimbabwe (11).The workload
for South Africa could not be calculated as the agency was
unable to provide data for products in 2019 due to mitigating
circumstances related to the unfit status of the organisation’s
premises. However, all six agencies reported that they had a
backlog of pending applications, therefore not all applications
were reviewed in the year that they were received. The analysis
also did not take into account the type of review to be conducted,
the competence of reviewers or other work such as post-approval
variations. It should be noted that in some of the countries due
to low numbers of staff, the same reviewer was responsible for
reviewing the quality, pre-clinical and clinical. The countries
with greater numbers of reviewers had one reviewer focusing on
quality and different reviewers for non-clinical and clinical.
Source of Funding
The Namibian agency was funded entirely by its government,
in Mozambique the greater proportion of agency funding was
from its government and a small percentage from other sources,
in South Africa, 70% of agency funding was provided by its
government and 30% from fees, in Tanzania, 12% of agency
funding was by its government, 76% from fees and 12% from
other sources, in Zambia, 95% of agency funding came from fees,
and 5% from other sources and the Zimbabwe agency was funded
entirely from fees. There is a significant range of fees applied for
the reviews of the products, depending on their category such as
new chemical entities, biologicals or generics. It is worth noting
that none of the agencies charged fees for scientific advice given
to applicants.
Namibia charged the lowest fees (333 USD) for new chemical
entities, while South Africa charged the highest (3,558 USD)
(Table 2). For biologicals, Namibia charged the lowest fees (333
USD) while Tanzania charged the highest (3,500 USD). For
generics, Namibia charged the lowest fees (333 USD), while
Zimbabwe charged the highest (2,500 USD). The agencies funded
largely or entirely by government charged the lowest fees, whilst
those relying on fees charged higher amounts with the exception
of South Africa which received 70% of its budget from the
Government, but charged fees comparable to Tanzania, Zambia,
and Zimbabwe agencies, which are funded largely through fees.
Part II – Key Milestones in the Review
Process
A standardised process map for the review and approval
of medicines is shown in Figure 1. This is a simplified
representation of the key milestones that are typically recorded
and monitored in the review of applications in a mature
regulatory system. The process map represents the review and
authorisation of a product that goes to approval after one review
cycle; however, in practice it usually takes more than one cycle
for a medicine to be approved, some agencies limit the number
of review cycles and opportunities given to applicants to respond
to questions.
Receipt and Validation Procedures
All six agencies validated applications received for completeness
in line with the applicable guidelines and statutory fees and all
six agencies recorded these two milestones. At this stage, the
pathway for review was determined; that is, either verification,
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Sithole et al. SADC Good Review Practices
TABLE 1 | Comparison of the country population, size of agencies and workload in 2019.
Country Mozambique Namibia South Africa Tanzania Zambia Zimbabwe
Population (millions) 29.5 2.6 58.8 58.6 17.4 16.2
Agency staff 83 26 170 103 120 143
Staff per million residents 2.8 10 2.9 1.8 6.9 8.8
Number of internal reviewers 5 4 57 45 19 18
Reviewers in agency staff 6% 15% 34% 44% 16% 13%
Total applications received 208 146 N/A* 873 585 203
Number of applications per reviewer 42 37 N/A* 19 31 11
*SAHPRA was unable to provide data for 2019 due to mitigating circumstances related to the unfit status of the organisation’s premises.
TABLE 2 | Comparison of fees charged and source of funding in 2019.
Country Mozambique Namibia South Africa Tanzania Zambia Zimbabwe
Source of funding* Large % government, 100% government 70% government 12% government; 95% fees 100% fees
small % other sources 30% Fees 76% fees; 12% other 5% other
Fees for review of a new
chemical entity (USD)
360 333 3,558 2,000 2,800 3,000
Fees for review of biologicals
(USD)
360 333 2,833 3,500 2,800 3,000
Fees for review of generics
(USD)
350 333 1,781 2,000 2,000 2,500
*Actual percentages vary year to year.
abridged or full review. Applications that passed validation were
placed in a queue awaiting scientific assessment. Incomplete
applications were removed from the queue and communication
was made to the applicant to provide the missing information.
Queue Time
The queue time is the time between the completion of
validation/acceptance for review of an application and the start
of the scientific assessment. This milestone was recorded by all
six agencies.
Primary Scientific Assessment
The start of the primary scientific assessment was recorded by
four of the six agencies, namely Mozambique, South Africa,
Tanzania, and Zimbabwe.
Questions to Applicants
All six agencies collected questions into a single batch after each
cycle of scientific assessment and sent these to the applicant. This
time is also referred to as “clock stop” or company time, when
the assessment is paused and the applicant given an opportunity
to respond to queries.
Review by Expert Committees
Five agencies made use of a panel of external experts known as the
expert committee during the review process with the agency staff
serving as the secretariat, with the exception of Mozambique. The
expert committee was involved after questions had been sent to
applicants in some agencies and in the other agencies, questions
were only sent to applicants after the committee procedure. The
external committees are referred to by different names in each of
the agencies; however, their function is similar. Namibia, South
Africa, Zambia, and Zimbabwe were mandated to follow the
Expert Committee’s opinion on a product and the Committee had
the responsibility for the marketing authorisation decision. For
Tanzania, the Committee made a recommendation, although the
final decision was made by the Director General. The decision
for marketing authorisation in Mozambique was made by the
Minister of Health.
Authorisation Procedure
Once an opinion or decision had been made on an application
for marketing authorisation, there was an administrative step
to finalise reports and update the labelling before the issuance
of the marketing authorisation. This step was performed in all
six countries.
Part III – Good Review Practices
For the purpose of clarity, GRevPs are presented under four
categories: quality measures; transparency and communications;
continuous improvement initiatives; and training and education.
Quality Measures
The quality measures evaluated in this comparative study
are listed in Table 3. Tanzania, Zambia and Zimbabwe
implemented all eight quality measures while the remaining
three countries (South Africa, Namibia, and Mozambique)
implemented six of the eight quality measures. Apart from
Mozambique, five agencies made use of expert scientific
committees as well as implementing a good review practice
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Sithole et al. SADC Good Review Practices
FIGURE 1 | Standardised review process map for regulatory agencies. This map represents the review and authorization of a product that goes to approval after one
review cycle. It should be noted that in some countries milestone G (committee procedure) may come before milestone D (questions to the applicant).
system (formally or informally). All of the six agencies had
standard operating procedures and assessment templates in
place. The assessment reports were prepared in English by
five agencies; whereas Mozambique prepared their reports in
Portuguese, their official language. An internal quality policy
was implemented by all agencies apart from Namibia. Four
agencies had dedicated quality departments, apart from Namibia
and South Africa, although South Africa has now appointed
a quality manager with a view to establishing a dedicated
quality department. All six agencies conducted peer review of
assessment reports.
Transparency and Communication
Transparency in the review process improves stakeholders’
(applicants as well as other stakeholders such as local agents
(which may be different from applicants), wholesalers, customers
who are potential applicants, ministry of health or the patients)
confidence in the system. It also assists the pharmaceutical
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Sithole et al. SADC Good Review Practices
TABLE 3 | Comparison of the quality measures implemented by the six regulatory authorities.
Quality measure Regulatory authority
Mozambique (6/8) Namibia (6/8) South Africa (6/8) Tanzania (8/8) Zambia (8/8) Zimbabwe (8/8)
Good review practice system XaX XaX Xa
Internal quality policy XX X X X
Standard operating procedures
for guidance of assessors
X X X X X X
Assessment templates X X X X X X
Peer review (internal) X X X X X
Dedicated quality department X✘ ✘bX X X
Scientific Committee X X X X X
Shared and joint reviews X X X X X X
aImplemented but not formally documented.
bA Quality Manager has now been appointed with a view to establishing a dedicated department.
TABLE 4 | Comparison of the transparency and communication parameters in the six agencies.
Quality measure Regulatory authority
Mozambique (4/9) Namibia (3/9) South Africa (8/9) Tanzania (4/9) Zambia (4/9) Zimbabwe (5/9)
Post-approval feedback to
applicant on quality of
submitted dossiers
X✘ ✘
Details of technical staff to
contact
XX✘ ✘
Pre-submission scientific advice
to industry
XaX Xc
Official guidelines to assist
industry
X X X X X X
Industry can track progress of
applications
X X Xa,b X X X
Publication of summary of
grounds on which approval was
granted
✘ ✘
Approval times X X X
Advisory committee meeting
dates
X✘ ✘
Approval of products X X X X X X
aImplemented informally.
bOnly for backlogged projects.
cOnly for local industry.
industry in preparing submissions and planning product launch
dates. Transparency saves a regulatory agency time and effort
as the industry would be able to access information and
requirements independently.
All six agencies assigned high priority to transparency
with stakeholders. Nine best practices in transparency and
communication with stakeholders were evaluated and used for
this comparison (Table 4). All agencies had official guidelines
and lists of approved products, which were made available to
the industry through their websites. Five of the agencies did
not provide post-approval feedback to applicants on quality of
submitted dossiers or publish advisory committee meeting dates
apart from South Africa. Four of the agencies did not provide
applicants with details of technical staff to contact during review
of their application apart from Mozambique and South Africa.
Four agencies did not provide pre-submission scientific advice
to the pharmaceutical companies except for South Africa, which
implemented this informally and Zimbabwe, which provided this
only for the local industry.
All six agencies allowed the industry to track progress of their
applications (Table 4) via email and telephone contact; however,
only Mozambique and Tanzania allowed applicants electronic
access to the status of their applications under review. None of
the agencies shared the full assessment report with applicants
or published a summary basis of approval; however, Tanzania
more recently has put in place a procedure for publishing public
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Sithole et al. SADC Good Review Practices
TABLE 5 | Comparison of continuous improvement initiatives in the six regulatory authorities.
Quality measure Regulatory authority
Mozambique (4/5) Namibia (2/5) South Africa (5/5) Tanzania (5/5) Zambia (4/5) Zimbabwe (5/5)
External quality Audits XX X X
Internal quality Audits XX X X X
Internal tracking Systems XXaX X X
Reviews of assessors’ feedback X X XaX X X
Reviews of stakeholders’ feedback X X X X X
aImplemented informally with no documented system.
assessment reports and these should be available in 2021. All six
agencies shared a list of questions after assessment and reasons
for refusal with the applicant. Only Tanzania published approval
times on their website, whereas South Africa and Zimbabwe
published these in their annual performance plan and annual
reports, respectively.
Continuous Improvement Initiatives
The continuous improvement initiatives included both internal
and external quality audits, an internal tracking system, as well
as reviews of assessors’ and stakeholders’ feedback. Tanzania
and Zimbabwe implemented all of the five initiatives, while
Zambia, Mozambique, and South Africa implemented four out
of the five initiatives. Namibia implemented only two out the
five initiatives (Table 5). Five agencies, apart from Namibia,
conducted internal quality audits. Five agencies had internal
tracking systems, except for Namibia. The assessors’ feedback was
reviewed by all six agencies; however, only Namibia, Tanzania,
Zambia, and Zimbabwe reviewed stakeholders’ feedback.
Training and Education
The measures evaluated under training and education contribute
to the development of personnel and the efficiency of the
regulatory review process. These measures are induction
training, on-the-job training, in-house and external courses,
international workshops, placements and secondments in other
regulatory authorities, post-graduate degrees, and collaboration
with other agencies. All six of the regulatory authorities in this
comparative study implemented all of the measures for training
and education. However, four agencies had formal training
programmes for assessors except for Mozambique and Namibia.
Part IV - Quality Decision-Making Practices
The decision-making process should be routinely measured
to ensure consistency and quality of decisions made in the
review and approval of medicines. Three of the agencies had
a framework in place that forms the basis of the decision to
approve or reject applications for new medicines, namely South
Africa, Tanzania, and Zambia. South Africa and Tanzania fully
incorporated all of the 10 quality decision-making practices
(QDMPs) developed by Donelan et al. as an aid to decision
making (7) into their frameworks and these were fully adhered to
in practice. Zambia incorporated six of the 10 practices into their
framework and fully adhered to four. Zimbabwe did not have
a documented decision-making framework, but used a decision
tree approach, fully adhering to seven out of the 10 decision-
making practices and partially adhering to three. Mozambique
and Namibia did not have a documented quality decision-making
framework. Interestingly, all six agencies stated that the decision-
making process could be improved, while the two agencies
without frameworks indicated their intention is to develop them
by 2022.
DISCUSSION
The aim of this study was to evaluate the regulatory review
processes of six countries in the SADC region that are active
members of the ZaZiBoNa collaborative medicines registration
initiative and compare the outcomes in order to identify
best practices. A common finding among the six regulatory
authorities was that participation in the ZaZiBoNa initiative has
improved the way in which they perform regulatory reviews
in their countries, and this highlights how one of the key
objectives of the initiative, which is to build expert capacity of
member countries is being realised. In addition to identifying
the differences and similarities in the processes in countries
currently participating in the ZaZiBoNa initiative as active
members, the results of this study will enable the regulatory
authorities, the majority of which are in low-to-middle-income
countries (LMICs), to benchmark processes, resources, and
capacity, something which in the past was difficult due to lack
of information in the public domain (8).
For industry, the results of this study provide an opportunity
to better understand the regulatory review processes in the six
agencies as well as the relevant challenges when planning future
submissions. The commitment to continuous improvement,
transparency and the desire to engage with industry shown by
all the agencies, reflects a new way of doing business that should
encourage further investment in terms of medicines development
and regulatory submissions made to these countries and the
SADC region as a whole.
Mature agencies such as Australia’s Therapeutic Goods
Administration and Health Canada’s Health Products and Food
Branch have a staff per million residents’ ratio in 2021 of 31
and 60, respectively (9). In contrast, all six agencies in this
study had a staff per million residents’ ratio <10, confirming
resource limitations faced by agencies in LMICs. In addition,
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Sithole et al. SADC Good Review Practices
a finding of this study was that there is a difference in human
resources available to conduct reviews in the six agencies within
the SADC region. Of note, countries with higher workloads
had no targets for the scientific assessment or overall approval
process, which points to overwhelmed resources. A workforce
should be adequate in skill and numbers for greater operational
efficiency. In addition, retention of skills after investing in staff
training is of paramount importance for agencies to deliver their
mandate in a timely manner.
The results of this study can be used as a baseline going
forward and presents an opportunity for agencies to re-examine
their processes to determine areas of improvement, particularly
where another agency with a comparable workload is able
to achieve shorter registration times. Routine recording of
the milestones studied here will enable the monitoring and
measurement of key performance indicators such as timelines
for validation, queue time, scientific assessment and the overall
approval, will enable the rapid identification of areas requiring
improvement and a proposal of gap-closing measures such as re-
engineering of processes or the injection of additional resources
by the agencies.
While most of the agencies in the study indicated that
resources could be optimised by placing reliance on mature
agencies, there is opportunity to further reduce timelines through
reliance on other agencies in the SADC region, as is already being
done by one of the agencies.
Although the ZaZiBoNa collaborative medicines registration
process was not directly evaluated in this study, it was possible
to see the reason for the difference in time to registration
among the participating countries after a recommendation
for approval by ZaZiBoNa. The initiative relies on countries
with differing capacities, resources and administrative processes
to carry out a significant part of the review process. There
is a need for a review of the current model used for
the ZaZiBoNa initiative in the next strategic period to
minimise the dependence on the country process and increase
operational efficiency.
Recommendations
As a result of this study several recommendations could be
considered by these agencies.
1. Performance measurement: In order to benchmark the
regulatory review process and monitor performance, agencies
should consider measuring and documenting the key
milestones and publishing the relevant timelines.
2. Improvement initiatives: Agencies could consider re-
examining their processes to evaluate where they can be
improved, and to learn from agencies with comparable
workloads who are achieving shorter timelines.
3. Sharing assessment reports: Agencies participating in
the ZaZiBoNa initiative should consider entering into
a memorandum of understanding to share unredacted
assessment reports for products that are not submitted
to the initiative, which constitute the majority of the
agencies’ workload.
4. Increased transparency and communication: Agencies
would benefit from implementing additional measures of
transparency and communication in line with international
best practices such as sharing of assessment reports with
applicants and publishing approval times, advisory committee
dates and a summary basis of approval.
5. Improved performance: Agencies should consider using
the results of this study to propose the provision of
adequate resources to improve timelines and patients’ access
to medicines.
6. Quality decisions: There is a need in some agencies for
training and capacity building in quality decision making.
7. ZaZiBoNa operating model: The participating countries
could consider reviewing the existing operational model for
improved efficiency.
CONCLUSIONS
This study incorporated fully autonomous and non-
autonomous agencies with both large and small
populations, providing a representative sample of
SADC countries. Those countries that were not able to
participate in the study and other countries in LMICs
could use the results to benchmark and improve their
own processes. If other agencies in the region were
to evaluate their review process using the approach
described in this study, they would also be able to
identify best practices, which in turn could improve their
regulatory performance.
DATA AVAILABILITY STATEMENT
The original contributions presented in the study are included
in the article/Supplementary Material, further inquiries can be
directed to the corresponding author.
ETHICS STATEMENT
The study was approved by the Health, Science, Engineering
and Technology ECDA, University of Hertfordshire [Reference
Protocol number: LMS/PGR/UH/04350].
AUTHOR CONTRIBUTIONS
TSith, SSa, and SW contributed to the design of the study,
implementation of the research, analysis of the results, and
drafting of the manuscript. GM, VC, TSito, SSh, JG, SP, TSe
AK, AF, ZM, and BM contributed to the implementation
of the research and critical review of the manuscript.
All authors contributed to the article and approved the
submitted version.
Frontiers in Medicine | www.frontiersin.org 8August 2021 | Volume 8 | Article 742181
Sithole et al. SADC Good Review Practices
ACKNOWLEDGMENTS
This research was underwritten by the Centre for Innovation in
Regulatory Science and was supported by an unrestricted grant
from the Bill and Melinda Gates Foundation.
SUPPLEMENTARY MATERIAL
The Supplementary Material for this article can be found
online at: https://www.frontiersin.org/articles/10.3389/fmed.
2021.742181/full#supplementary-material
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Conflict of Interest: The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could be construed as a
potential conflict of interest.
Publisher’s Note: All claims expressed in this article are solely those of the authors
and do not necessarily represent those of their affiliated organizations, or those of
the publisher, the editors and the reviewers. Any product that may be evaluated in
this article, or claim that may be made by its manufacturer, is not guaranteed or
endorsed by the publisher.
Copyright © 2021 Sithole, Mahlangu, Capote, Sitoie, Shifotoka, Gaeseb, Padayachee,
Sehloho, Khea, Fimbo, Munkombwe, Mwale, Salek and Walker. This is an open-
access article distributed under the terms of the Creative Commons Attribution
License (CC BY). The use, distribution or reproduction in other forums is permitted,
provided the original author(s) and the copyright owner(s) are credited and that the
original publication in this journal is cited, in accordance with accepted academic
practice. No use, distribution or reproduction is permitted which does not comply
with these terms.
Frontiers in Medicine | www.frontiersin.org 9August 2021 | Volume 8 | Article 742181
... The four countries signed memoranda of understanding agreeing to participate in the initiative and agreed that this would be a requirement for other SADC countries wishing to join the initiative (1). Today, all 16 SADC countries participate in the ZaZiBoNa initiative, either as active members or non-active members depending on their capacity to conduct dossier assessments and good manufacturing practice (GMP) inspections (1,4). ZaZiBoNa was absorbed into the SADC medicines registration harmonisation project in 2015 which, together with other regional economic communities in Africa, is overseen by the African Medicines Regulatory Harmonisation Initiative (AMRH) (5). ...
... Despite these successes, some challenges have been identified through feedback from applicants such as differences in time to implement ZaZiBoNa recommendations by the participating countries (1,4). This is not surprising, as the participating countries have some differences in their registration processes; for example, frequency of expert Committee meetings (4,11), which may affect the implementation of the ZaZiBoNa recommendations. ...
... Despite these successes, some challenges have been identified through feedback from applicants such as differences in time to implement ZaZiBoNa recommendations by the participating countries (1,4). This is not surprising, as the participating countries have some differences in their registration processes; for example, frequency of expert Committee meetings (4,11), which may affect the implementation of the ZaZiBoNa recommendations. ...
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... Views of the regulators (15) and industry were compared and there was agreement on the challenges such as lack of information for applicants on country websites, failure by applicants to meet deadlines for submission of responses, Interestingly, only a minority of the regulators and industry were of the view that self-funding by countries created a sustainable resource base for this initiative; therefore, there is still a need for partner support or other sources of funding at present. This is supported by studies in the literature highlighting the inadequacy of resources currently available to authorities in lowto middle-income countries (16)(17)(18)(19)(20). Challenges highlighted by the industry but not identified in the regulators study (15) are the difficulties faced by applicants when they need to follow up on pending dossiers/applications or seek arbitration in situations in which individual authorities were uncooperative. ...
... Although the ZaZiBoNa initiative has been in operation for8 years, the process for submission in some countries remains unclear to applicants (15). This, in addition to a number of other challenges identfied in this study such as failure by some countries to register medicines and issue GMP certificates within the set timelines after a ZaZiBoNa recommendation, can be attributed to the participating authorities having differing capacities (14,18). Centralised submission and tracking were therefore proposed by both regulators and industry as ways to improve the effectiveness and efficiency of this initiative. ...
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Background: Benchmarking regulatory systems of low- and middle-income countries with mature systems of comparable size provides an opportunity to identify gaps, enhance review quality, and reduce registration timelines, thereby improving patients' access to medicines. The aim of this study was to compare the medicines registration process of the Medicines Control Authority of Zimbabwe (MCAZ) with the regulatory processes in Australia, Canada, Singapore, and Switzerland. Methods: A questionnaire that standardizes the review process, allowing key milestones, activities and practices of the five regulatory authorities was completed by a senior member of the divisions responsible for issuing marketing authorizations. Results: The MCAZ has far fewer resources than the regulatory authorities in the comparator countries, but employs three review models, which is in line with international best practice. The MCAZ registration process is similar to the comparator countries in key milestones identified and monitored, but differs in the target timelines for these milestones. The MCAZ is comparable to the comparator authorities in implementing the majority of good review practices, although it significantly lags behind in transparency and communication. Conclusion: This study identified the MCAZ strengths and opportunities for improvement, which if implemented, will enable the achievement of its vision to be a leading regulatory authority in Africa.
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ZAZIBONA collaboration
  • F Masekela
Masekela F. ZAZIBONA collaboration. In: TWINZ Meeting of Pharmaceutical Industry (2020).
Adjusted indirect treatment comparisons of bioequivalence studies. Doctoral thesis
  • L Gwaza
Gwaza L. Adjusted indirect treatment comparisons of bioequivalence studies. Doctoral thesis. Utrecht University, Utrecht, Netherlands (2016). Available online at: http://dspace.library.uu.nl/handle/1874/337474 (accessed August 12, 2021).