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Regulatory Authority Evaluation of the Effectiveness and Efficiency of the ZaZiBoNa Collaborative Medicines Registration Initiative: The Way Forward

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Introduction ZaZiBoNa, the work-sharing initiative in the Southern African Development Community (SADC) that has been in operation for 8 years has successfully assessed over 300 dossiers/applications, with an overall median time to recommendation of 12 months. All 16 SADC countries participate in the initiative as either active or non-active members. While the successes of ZaZiBoNa are evident, some challenges still exist. The aim of this study was to solicit the views of the participating authorities on the effectiveness and efficiency of the current operating model of the ZaZiBoNa initiative. Methods Data were collected in 2021 using the Process, Effectiveness and Efficiency Rating (PEER) questionnaire developed by the authors. The questionnaire was completed by the focal person in each country and approved by the head of the authority. Results ZaZiBoNa serves as a platform for work sharing, information exchange, capacity building and harmonisation of registration requirements. One of the benefits to regulators has been the improvement in the capacity to conduct assessments. Manufacturers have benefited from compiling one package (modules 2–5) for the initial submission as well as a single response package to the consolidated list of questions, which saves time and resources. Respondents were of the view that patients have benefited as the ZaZiBoNa has contributed to an improved availability and accessibility to quality-assured medicines. Some of the challenges identified were the inadequacy of resources and differences in time to the implementation of ZaZiBoNa recommendations by the individual countries. The establishment of a regional unit hosted in one of the member countries to enable centralised submission and coordination was identified as the best strategy to improve the effectiveness and efficiency of the initiative in the interim, with the long-term goal being the establishment of a regional medicines authority. Conclusion The study identified the strengths of the ZaZiBoNa initiative as well as the opportunities for improvement. The recommendations made would further strengthen this initiative.
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ORIGINAL RESEARCH
published: 25 April 2022
doi: 10.3389/fmed.2022.898743
Edited by:
Steffen Thirstrup,
NDA Advisory Services Ltd.,
United Kingdom
Reviewed by:
Christine Årdal,
Norwegian Institute of Public Health
(NIPH), Norway
Birka Martha Luise Lehmann,
University of Bonn, Germany
*Correspondence:
Stuart Walker
swalker@clarivate.com
Specialty section:
This article was submitted to
Regulatory Science,
a section of the journal
Frontiers in Medicine
Received: 17 March 2022
Accepted: 01 April 2022
Published: 25 April 2022
Citation:
Sithole T, Mahlangu G, Walker S
and Salek S (2022) Regulatory
Authority Evaluation of the
Effectiveness and Efficiency of the
ZaZiBoNa Collaborative Medicines
Registration Initiative: The Way
Forward. Front. Med. 9:898743.
doi: 10.3389/fmed.2022.898743
Regulatory Authority Evaluation of
the Effectiveness and Efficiency of
the ZaZiBoNa Collaborative
Medicines Registration Initiative: The
Way Forward
Tariro Sithole1,2, Gugu Mahlangu2, Stuart Walker1,3*and Sam Salek1,4
1School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom, 2Medicines Control Authority
of Zimbabwe, Harare, Zimbabwe, 3Centre for Innovation in Regulatory Science, London, United Kingdom, 4Institute
for Medicines Development, Cardiff, United Kingdom
Introduction: ZaZiBoNa, the work-sharing initiative in the Southern African
Development Community (SADC) that has been in operation for 8 years has
successfully assessed over 300 dossiers/applications, with an overall median time to
recommendation of 12 months. All 16 SADC countries participate in the initiative as
either active or non-active members. While the successes of ZaZiBoNa are evident,
some challenges still exist. The aim of this study was to solicit the views of the
participating authorities on the effectiveness and efficiency of the current operating
model of the ZaZiBoNa initiative.
Methods: Data were collected in 2021 using the Process, Effectiveness and
Efficiency Rating (PEER) questionnaire developed by the authors. The questionnaire
was completed by the focal person in each country and approved by the head
of the authority.
Results: ZaZiBoNa serves as a platform for work sharing, information exchange,
capacity building and harmonisation of registration requirements. One of the benefits
to regulators has been the improvement in the capacity to conduct assessments.
Manufacturers have benefited from compiling one package (modules 2–5) for the initial
submission as well as a single response package to the consolidated list of questions,
which saves time and resources. Respondents were of the view that patients have
benefited as the ZaZiBoNa has contributed to an improved availability and accessibility
to quality-assured medicines. Some of the challenges identified were the inadequacy of
resources and differences in time to the implementation of ZaZiBoNa recommendations
by the individual countries. The establishment of a regional unit hosted in one
of the member countries to enable centralised submission and coordination was
identified as the best strategy to improve the effectiveness and efficiency of the
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Sithole et al. ZaZiBoNa Regulatory Evaluation
initiative in the interim, with the long-term goal being the establishment of a regional
medicines authority.
Conclusion: The study identified the strengths of the ZaZiBoNa initiative as well as the
opportunities for improvement. The recommendations made would further strengthen
this initiative.
Keywords: ZaZiBoNa, regulatory harmonisation, work sharing, effectiveness, efficiency
INTRODUCTION
In October 2013, the inaugural meeting of the ZaZiBoNa
collaborative medicines registration initiative was held in
Windhoek, Namibia (1). Named using the first two letters
of the four founding countries in the Southern African
Development Community (SADC), namely Zambia, Zimbabwe,
Botswana and Namibia (2), ZaZiBoNa was a vision of the
Heads of Agencies of those countries, with the support of
the World Health Organization (WHO) prequalification team
and the Southern African Programme on Access to Medicines
and Diagnostics (SAPAM) (1). The main objectives of the
ZaZiBoNa initiative were “a reduced workload, reduction in
timelines to registration, the development of mutual trust
and confidence in regulatory collaboration and to provide a
platform for training and collaboration in other regulatory
fields” (1).
Prior to the launch of the initiative, the national medicines
regulatory authorities in SADC operated in isolation, despite
facing similar challenges such as large registration backlogs
that resulted in long registration times, hindering access to
critical medicines by their populations (3). Poor retention
of human resources, and inadequate capacity to assess
certain types of medicinal products were also common
challenges faced by the countries, making a collaborative
approach involving sharing of resources and expertise not
only desirable but absolutely imperative. 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).
In the current model of the ZaZiBoNa initiative, applicants
simultaneously submit applications for registration and
pay fees to each of the countries in which they wish to
Abbreviations: AMRH, African Medicines Regulatory Harmonisation Initiative;
EAC, East African Community; PEER, Process, Effectiveness and Efficiency Rating;
SADC, Southern African Development Community; SAPAM, Southern African
Programme on Access to Medicines and Diagnostics; WHO, World Health
Organization.
market their medicinal product (1,6,7). The assessment
of dossiers/applications is carried out using a rapporteur
and co-rapporteur before consideration of the report
by a group of assessors from all the active member
countries. In the absence of a regional legal framework,
ZaZiBoNa does not have centralised submissions or
approvals/registrations (1). Therefore, once the evaluation
is concluded, an assessment report with a recommendation
and a consolidated list of questions is produced (1) and
communication of the list of questions to the applicants
as well as the final decision on the registration/marketing
authorisation of medicinal products is left to the individual
participating countries (1,6). The process map is illustrated
in Figure 1 (1). The Heads of Agencies serve as a governing
body and countries participate in the initiative through
multilateral agreements.
A key success of ZaZiBoNa has been its ability to continue
operating with limited resources, with participating countries
also contributing financially to the initiative since its inception
(1). Another important initiative accomplishment is the
achievement of shorter timelines for the 333 dossiers/applications
that have been assessed to date (December 2021) compared
with the timelines achieved by some of the participating
countries using their national procedures (6,8). For example,
ZaZiBoNa has an overall median time to recommendation of
12 months (9), whereas some of the participating countries
had approval times of over 650 days in 2020 (10). The
gap in regulatory capacity among participating countries
has also been reduced through the training of assessors
and inspectors, bringing further harmonisation in the
way assessments and GMP inspections are conducted in
the SADC region.
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.
Sithole and colleagues therefore recommended a review of
the ZaZiBoNa operating model to identify opportunities for
improved efficiency (4). The aim of this study was to solicit the
views of the authorities on the effectiveness and efficiency of
the current operating model of the ZaZiBoNa initiative. To our
knowledge, no similar study has been conducted or published
in the literature.
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FIGURE 1 | ZaZiBoNa process map. Reprinted from Sithole et al. (1) under a Creative Commons Attribution 4.0 International License. Copyright, the authors, 2020.
STUDY OBJECTIVES
The Study Objectives Were to
1. Obtain the views of the individual medicines’ regulatory
authorities of the ZaZiBoNa work-sharing initiative
2. Identify the challenges experienced by individual
authorities since the inception of the ZaZiBoNa initiative
3. Determine the strengths and weaknesses of the initiative
4. Identify the ways of improving the performance of the
initiative
5. Envisage the strategy for moving forward
MATERIALS AND METHODS
Study Participants
All nine active members of the ZaZiBoNa initiative participated
in the study translating to a response rate of 100%. These are,
Botswana, Democratic Republic of Congo, Malawi, Mozambique,
Namibia, South Africa, Tanzania, Zambia and Zimbabwe. Active
member status is determined by “the capacity to conduct
assessments and GMP inspections” (4).
Data Collection
Data were collected in August 2021 using the Process,
Effectiveness and Efficiency Rating questionnaire (PEER)
developed by the authors. The questionnaire was completed
by the focal person in each country and approved by the head
of the authority. The questionnaire comprised five sections
under the headings Demographics; Benefits of the ZaZiBoNa
initiative; Challenges of the ZaZiBoNa initiative; Improving the
performance (effectiveness and efficiency) of the work-sharing
programme; and Envisaging the strategy for moving forward.
To examine the applicability and practicality of the PEER
questionnaire, it was piloted with two member authorities in
July 2021 prior to undertaking the main study. Subsequently,
to establish the content validity and relevance of the PEER
questionnaire, an additional questionnaire was completed and
semi-structured interviews were carried out in September 2021
with each of the member authorities following completion of
the questionnaire.
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 are presented in five
parts, matching the sections of the questionnaire: Part I—
Demographics and authority resources; Part II—Benefits of
the ZaZiBoNa initiative; Part III—Challenges of the ZaZiBoNa
initiative; Part IV—Improving the performance of the work-
sharing programme; and Part V—Envisaging the strategy
for moving forward.
Part I—Demographics and Authority
Resources
The study respondents’ age ranged from 31 to 49 years, with
a range of regulatory experience from 4 to 16 years. Five
of the respondents were female and 4 were male. Authority
resources, including the number of authority assessors assigned
to ZaZiBoNa reviews are listed in Table 1.
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TABLE 1 | Authority resources.
Botswana D.R congo Malawi Mozambique Namibia South Africa Tanzania Zambia Zimbabwe
Number of staff 93 300 53 87 17 237#290#120 135
Number of assessors* 9 75 8 9 8 33 59 18 20
Number of assessors
involved in ZaZiBoNa
9 4 4 5 6 12 20 14 20
*Internal; #Permanent.
Part II—Benefits of the ZaZiBoNa
Initiative
Benefits of the ZaZiBoNA Initiative
Information sharing among regulators (9/9), building of
capacity for assessments (9/9) and harmonisation of registration
requirements across the region (8/9) were identified as the top
3 benefits of the ZaZiBoNa initiative by the countries. However,
less than a third of the countries believed that assessment through
ZaZiBoNa resulted in shorter timelines for approval of medicines
(2/9) or that the operating model was clear (2/9) (Figure 2).
Strengths of the ZaZiBoNa Process at Country Level
The availability of information on the submission process and
timelines for ZaZiBoNa dossiers/applications on the country
website was selected as the top strength at a country level by most
of the countries (6/9). The availability of a separate register and
tracking, priority review and regular committee meetings, which
enabled the timely recommendation of dossiers/applications
were also identified as strengths by the majority of countries (5/9).
However, less than one third of the countries (2/9) published
a list of medicinal products approved under ZaZiBoNa on
their website, which could be regarded as a weakness of the
initiative
Benefits of the ZaZiBoNa Initiative to Member
Countries (Regulators)
The majority of the countries agreed that the ZaZiBoNa initiative
provided them with benefits that include training, which has
improved the performance of the assessors (9/9), a platform
for interaction and information exchange with other regulators
(9/9), an improvement in the quality of dossiers submitted (8/9)
and the ability to apply high standards of assessment regardless
of the size of the country or maturity of regulatory authority
(7/9). However, less than one third of the countries (2/9)
believed that the sharing of the workload through ZaZiBoNa
resulted in shorter timelines for approval than in the individual
countries, confirming the observation that this is a weakness
of the initiative.
Benefits of the ZaZiBoNa Initiative to Applicants
Benefits to applicants selected by countries included reduction of
the burden of compiling several dossiers for different countries,
as only one dossier (modules 2–5) is required for submission
to multiple countries through ZaZiBoNa (8/9) and savings in
time and resources as the same list of questions is received from
multiple countries enabling compilation of a single response
package (9/9) with simultaneous access to various markets (9/9).
However, only one third of the respondents (3/9) believed
that applicants were receiving the promised benefit of shorter
timelines for approval compared with timelines achieved for the
individual countries (Figure 3).
Benefits of the ZaZiBoNa Initiative to Patients
Increased availability and access to quality-assured medicines
(7/9) were identified as the benefits of the ZaZiBoNa initiative
for patients by the majority of the countries, although that access
was not regarded as always being faster than through individual
countries (6/9). However, less than one third of the countries
(2/9) were of the view that the initiative resulted in reduced
prices of medicines.
Part III—Challenges of the ZaZiBoNa
Initiative
Challenges of the ZaZiBoNa Initiative
The top two challenges of the ZaZiBoNa initiative that were
selected were the lack of centralised submission and tracking
(8/9) and dependence on the member country processes for
communication with applicants and expert committees (7/9).
An unequal workload among member countries (5/9), lack
of jurisdictional power (5/9), a low or decreasing number of
applications (4/9) and lack of detailed information on the
process for applicants (3/9) were also identified as challenges
by the countries.
Challenges at a Country Level in Assessing
ZaZiBoNa Dossiers/Applications
Inadequate human resources (8/9) and the failure by applicants
to adhere to deadlines for response to questions (7/9) were cited
as the greatest challenges at a country level. Additionally, the
majority of the countries (5/9) were of the view that failure by
manufacturers to follow the requirement to submit the exact
same dossier to all countries of interest was an issue. The other
challenges identified were poor record keeping and tracking
(3/9), unpredictable scheduling of expert committee meetings
(2/9), lack of buy-in from expert committees (1/9) and a failure
by authorities to designate ZaZiBoNa assessments as part of the
authority’s workload (1/9).
Challenges for Applicants Submitting Applications to
the ZaZiBoNa Initiative
The majority of the countries agreed that differing labelling
requirements in participating countries (8/9) and lack of
information on individual country and ZaZiBoNa websites about
the process, milestones, timelines and pending and approved
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FIGURE 2 | Benefits of the ZaZiBoNa initiative according to regulatory authority respondents.
FIGURE 3 | Benefits of the ZaZiBoNa initiative to applicants according to regulatory authority respondents.
medicinal products (7/9) were the greatest challenges faced
by applicants with the initiative. Additionally, most of the
countries were of the view that the ZaZiBoNa process is
more stringent than some country processes (6/9), presenting
a challenge for applicants. Other issues identified were lack
of clarity about the process for submission and follow-
up in each country (4/9) and differences in time to the
implementation of ZaZiBoNa recommendations by member
countries (3/9) (Figure 4).
Part IV—Improving Performance
(Effectiveness and Efficiency)
Ways to Improve the Effectiveness of the ZaZiBoNa
Initiative
Some of the ways identified by the countries to improve
effectiveness of the initiative included decision-making
transparency; for example, publishing public assessment reports
(7/9), listing approved medicinal products (6/9), minimising
the need for country-specific documents (5/9), engagement and
interaction with stakeholders (5/9), use of risk-based approaches
e.g., reliance pathways (5/9), consistency in application of
guidelines and decisions (5/9), making information that might
help applicants in managing their submissions publicly available
(5/9) and publishing lists of pending dossiers/applications
(3/9) (Figure 5).
Ways to Improve the Efficiency of the ZaZiBoNa
Initiative
Improved central tracking of ZaZiBoNa dossiers/applications
(8/9), a centralised system for submission of applications and
communication with applicants (7/9), use of robust information
technology systems (6/9), compliance with target timelines
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FIGURE 4 | Challenges for applicants submitting applications to the ZaZiBoNa initiative according to regulatory authority respondents.
by measuring and monitoring each milestone in the review
process (6/9), specific and clear requirements made easily
available to applicants (6/9), improved resources; for example,
number of assessors (5/9) and transparency on metrics and
statistics; for example, percentage completed within timeline
(2/9) were selected as ways to improve the efficiency of the
initiative (Figure 6).
Part V—Strategies for Moving Forward
The establishment of a regional unit hosted in one of the member
states, to centrally receive and track ZaZiBoNa applications and
be responsible for allocating work, apportioning the applicable
fees to countries, tracking applications and communicating with
applicants was selected by the majority of countries (8/9) as
the best strategy moving forward in the interim. The majority
of countries (7/9) were also of the view that to continue with
the current operating model was the least effective strategy. All
countries expressed the position that the establishment of a
SADC regional medicines authority would be the best strategy,
if it were legally possible, to address the challenges and areas
requiring improvement in the initiative.
DISCUSSION
The results of this study show that the ZaZiBoNa initiative
has achieved the majority of its objectives, which included
facilitating greater information sharing and harmonisation of
registration requirements. The capacity of countries to conduct
assessments and inspections has markedly improved as a result
of their participation in this initiative (4,10). Reliance is being
implemented within the initiative, as countries can quickly
approve dossiers/applications that they have not reviewed but
whose reports can be accessed through ZaZiBoNa. One of the key
objectives of the ZaZiBoNa initiative was to reduce timelines for
the approval of medicines, with a target median time of 9 months
inclusive of the applicant’s time and the study results underscored
the expected benefit to applicants of reduced timelines. However,
the majority of countries did not believe that shorter timelines
were being achieved and this may be problematic in the future, as
it can negatively affect applicants’ interest and motivation to use
this process. The additional challenges faced by applicants and
acknowledged by the countries need to be addressed in order to
make the initiative more attractive.
Clear communication of timelines for each milestone with
applicants as well as the requirements for dossiers/applications
to be reviewed will increase the applicants’ confidence in the
process. At present, not all the participating countries have full
information on ZaZiBoNa on their websites, including contact
details of the focal person for follow-up. This is information that
would be useful for applicants who may be planning submissions
to ZaZiBoNa and is in place with other successful global work-
sharing initiatives (8,12). Some of the shortcomings at a country
level can be attributed to inadequate resources, which may also
impact the quality of the assessments. A weakness of this initiative
that was identified from the study was the use of inexperienced
assessors and the unavailability of experienced assessors in some
of the countries to carry out the ZaZiBoNa work. The initiative
should have standard operating procedures in place to ensure that
only competent assessors and inspectors are seconded by the
respective countries to participate in the initiative, an approach
modelled on the Committee for Medicinal Products for Human
Use (CHMP) of the European Medicines Agency (11).
It has been established that ZaZiBoNa uses an operating
model similar to other global work-sharing initiatives (1214);
however, challenges have been identified. This could be due to
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FIGURE 5 | Ways to improve the effectiveness of the ZaZiBoNa initiative according to regulatory authority respondents.
FIGURE 6 | Ways to improve the efficiency of the ZaZiBoNa initiative according to regulatory authority respondents.
the significantly lower resources; for example, the number of
assessors, available to ZaZiBoNa countries when compared with
countries in the other initiatives. Most of the active member
countries in ZaZiBoNa are faced with the challenge of limited
resources and a high number of applications (4,10,1517)
for the national procedure, which negatively impacts the work-
sharing initiative. The use of a regional unit to coordinate
assessments would also assist in addressing the identified
challenges, particularly in a resource-constrained setting. In the
long term, the establishment of a SADC regional medicines
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authority would be preferable and would address the challenge of
the lack of jurisdictional power identified in this study.
Key recommendations to improve the effectiveness and
efficiency of the ZaZiBoNa work-sharing initiative include:
Measuring and monitoring regulatory timelines: The
ZaZiBoNa initiative has measured and published the
review timelines for the 333 dossiers/applications reviewed
to date. This needs to be improved to include the
monitoring, measuring and publication of the time to
finalisation of ZaZiBoNa dossiers/applications in the
individual participating countries.
Capacity building and training of assessors: The
ZaZiBoNa initiative has successfully facilitated and enabled
the training of assessors in the 16 SADC countries. Going
forward, the training and capacity-building activities
should be separated from assessment activities, which
will enable countries to second only competent assessors
and inspectors, improving the effectiveness and efficiency
of the initiative.
Information for applicants: Requirements, guidelines,
timelines and the process for submission of
dossiers/applications to ZaZiBoNa should be made
available on all participating country websites, including
the contact details of the focal person.
Transparency of process and decision making: Since 2017,
the ZaZiBoNa initiative has prepared scientific summaries
for approved medicinal products. These should be made
available on the ZaZiBoNa and country websites.
Establishment of a regional medicines authority: In the
short-term, a regional unit hosted in one of the member
countries to centrally receive ZaZiBoNa applications and
coordinate communication with applicants should be
piloted with the goal to establish a SADC regional
medicines authority in the near future.
Study Limitations
The scope of this study was limited to the ZaZiBoNa initiative’s
process and operating model. In future, it would be helpful
to obtain quantitative data to support these views which
would include actual metrics of the time taken to register
the medicinal products in the individual countries after a
ZaZiBoNa recommendation. The status of commercialisation
and pricing of the medicinal products in the individual countries
as well as the factors influencing this could be the subject
of a future study.
CONCLUSION
This study identified the strengths of the ZaZiBoNa
initiative as well as the opportunities for improvement. The
recommendations should further strengthen this initiative,
enabling it to fulfil one of its mandates, to ensure timely patient
access to quality medicines in the SADC region. Although this
was not the focus of this study, the SADC member states are
encouraged to sign and ratify the African Medicines Agency
(AMA) treaty, as that is considered the future of medicines
regulation in Africa.
DATA AVAILABILITY STATEMENT
The raw data supporting the conclusions of this article will be
made available by the authors, on request.
AUTHOR CONTRIBUTIONS
TS designed the study, collected, and analysed the data and wrote
the first draft of the manuscript. GM interpreted the results and
reviewed subsequent drafts of the manuscript. SW designed the
study, interpreted the results, and reviewed subsequent drafts of
the manuscript. SS designed the study, interpreted the results,
and reviewed subsequent drafts of the manuscript. All authors
contributed to the article and approved the submitted version.
FUNDING
We wish to acknowledge the Jenny Greenhorn Memorial
Scholarship for supporting the Ph.D. project. This research was
also supported by an unrestricted grant from the Bill and Melinda
Gates Foundation.
ACKNOWLEDGMENTS
We wish to thank the ZaZiBoNa focal persons and Heads
of Agencies of the Botswana Medicines Regulatory Authority
(Stephen Ghanie and Ntsetselele Kago), Direction de la
Pharmacie and du Médicament, Health Ministry of the
Democratic Republic of Congo (Donatien Kabamb Kabey and
Laurent Tshimpaka), Pharmacy Medicines and Poisons Board
of Malawi (Charles Chimenya and Edwin Chipala), National
Medicines Regulatory Authority of Mozambique (Tania Sitoie
and Nazalia Macuvele), Namibia Medicines Regulatory Council
in the Ministry of Health (Johannes Gaeseb and Johanna
Wilbard) South African Health Products Regulatory Agency
(Boitumelo Semete and Mphako Brighton Ratlabyana), Tanzania
Medicines and Medical Devices Authority (Adam Fimbo and
Alex Juma), Zambia Medicines Regulatory Authority (Makomani
Siyanga and Rona Njovu) and the Medicines Control Authority
of Zimbabwe (Richard Rukwata and Grace Matimba).
SUPPLEMENTARY MATERIAL
The Supplementary Material for this article can be found
online at: https://www.frontiersin.org/articles/10.3389/fmed.
2022.898743/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
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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 © 2022 Sithole, Mahlangu, Walker and Salek. This is an open-access
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Frontiers in Medicine | www.frontiersin.org 9April 2022 | Volume 9 | Article 898743
... Following the successful assessment of the ZaZiBoNa and EAC-MRH initiatives in 2021 and the impending launch of the African Medicines Agency, it is timely that the WA-MRH initiative is assessed at this time and hence the implementation of this study (Sithole et al., 2022;Ngum et al., 2022). The study aimed to assess the effectiveness and efficiency of the West Africa Medicines Regulatory Harmonization Initiative by the member countries. ...
... A solution for this shortcoming should therefore be given a high priority. Lessons can be taken from the EAC-MRH initiative which has achieved the important benefit of shorter timelines for approval since this was not an outcome for the ZaZiBoNa initiative (Sithole et al., 2022;Ngum et al., 2022). This will enhance the reported benefit of the WA-MRH initiative to patients at the country and regional levels of having quicker access to quality-assured medicines. ...
... It is important to note that other challenges of the WA-MRH initiative such as lack of centralised submission and tracking and a poor IT infrastructure to support dossier submissions and the assessment process can be considered as common with the other MRH initiatives in Africa as these challenges were also reported by Sithole and others and also by Ngum and others (Sithole et al., 2022;Ngum et al., 2022). In addition to providing a robust IT infrastructure to track dossier assessments, the competence of assessors should be adequate to perform to international standards and the fast-tracking of applications should be entertained only when public health rather than the manufacturers' wishes requires such prioritisation (Hill and Johnson, 2004). ...
Article
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Background: The West Africa Health Organization launched the West Africa Medicines Regulatory Harmonization Project (WA-MRH) in 2017 with the overarching objective to improve the availability of high-quality, safe and effective medicines and vaccines by the 15 countries in the Economic Community of West African States region. Although this project has made significant progress towards the realisation of its goals, challenges still remain. The aims of this study were to evaluate the effectiveness and efficiency of the WA-MRH, examine what challenges are being encountered and identify strategies that would strengthen the process for realising the initiative’s goals. Methods: The Process Effectiveness and Efficiency Rating (PEER) questionnaire was used to collect data from assessors representing the seven active NMRAs in the joint assessment procedure that identified the benefits, challenges and recommendations for improving the performance of the WA-MRH project. Results: The benefits of the joint assessment procedure include time savings to manufacturers resulting from submitting one dossier and the same response package to multiple countries resulting in access to the multiple African markets within the same timeframe. Additionally, some of the NMRAs have been able to strengthen their technical capacity as a result of this initiative. Key challenges to the project include the lack of a robust information technology system that would enable dossier tracking and constraints in human resources needed to support dossier submissions and the assessment process. Conclusion: This study identified the strengths of the WA-MRH initiative as well as strategies for improvement and achievement of its objectives. The centralised submission of a dossier and its tracking is key to the regulatory assessment process. This research has demonstrated that amongst other considerations, a robust information technology system, coupled with the necessary human resource capacity would greatly enhance the effectiveness and efficiency of the WA-MRH initiative.
... The results of this study show that applicants perceive that there has been a high degree of success and benefit from the ZaZiBoNa initiative for applicants, patients and regulators. A similar study was conducted with regulators (15) and the responses compared. Regulators and industry commonly agreed that information sharing among regulators and harmonisation of registration requirements across the region were the top benefits of the ZaZiBoNa initiative. ...
... Both regulators and pharmaceutical industry were of the view that the initiative has resulted in greater access to quality-assured medicines by patients, although there was a difference in opinion regarding the time that this is taking. A number of applicants were of the view that ZaZiBoNa resulted in shorter timelines, while only a minority of regulators believed that this was a benefit (15). Further investigation is required to understand why the initiative is not resulting in reduced prices of medicines for patients, since both regulators and industry acknowledge that time, resources and the effort required to get medicines approved has been reduced. ...
... 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. The challenges identified in this study are not unique to this initiative, as they have been identified for other regions such as the East African Community, with applicants indicating that the goal of harmonisation, which was to ensure quicker access to qualityassured medicines was not always being met (21). ...
Article
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Introduction The common technical document (CTD) format harmonised the requirements for the registration of medicines, which had traditionally differed from country to country, making it possible for countries to collaborate and conduct joint reviews of applications. One such collaborative medicines registration initiative is the Southern African Development Community ZaZiBoNa, established in 2013. A recent study was carried out with the nine active member regulatory authorities of the ZaZiBoNa to determine their views on its operational effectiveness and efficiency. Having obtained the authorities’ views, the aim of this study was to evaluate the effectiveness and efficiency of the current operating model of the ZaZiBoNa initiative including the challenges it faces as well as identifying opportunities for improvement from the applicants’ perspective. Methods Applicants who had submitted registration/marketing authorisation applications for assessment under the ZaZiBoNa initiative during 2017–2021 were recruited into the study. Data was collected in 2021 using the Process, Effectiveness and Efficiency rating questionnaire (PEER-IND) developed by the authors. The questionnaire was completed by a representative responsible for ZaZiBoNa submissions in each company. Results The pharmaceutical industry was of the view that the ZaZiBoNa initiative has achieved shorter timelines for approval of medicines, resulting in increased availability of quality-assured medicines for patients in the SADC region. Harmonisation of registration requirements and joint reviews have reduced the workload for both the pharmaceutical industry and the regulatory authorities. Some of the challenges identified were the lack of a centralised submission and tracking system, and the lack of information for applicants on the process for submission of ZaZiBoNa dossiers/applications in the individual countries, including contact details of the focal person. The establishment of a regional unit hosted in one of the member countries to centrally receive and track ZaZiBoNa dossiers/applications was identified as the best strategy for moving forward in the interim with the long-term goal being the establishment of a regional medicines authority. Conclusion There was consensus between the pharmaceutical industry and the regulatory authorities as to the way forward to improve the effectiveness and efficiency of the ZaZiBoNa initiative. Implementation of the recommendations identified in this study will lead to enhanced regulatory performance.
... This decision has borne fruit, as we report the results of this study show that the initiatives have successfully developed regional guidelines and templates and conducted joint reviews of many products. 8,13,23 The initiatives also resulted in building the capacity of member states; for example, in the EAC, Burundi, Rwanda, and Zanzibar were supported in the establishment of semi-autonomous national regulatory authorities that previously did not exist. 24 In SADC, Angola, and Mozambique were also supported in the establishment of semi-autonomous national regulatory authorities. ...
Article
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Background: The African Medicines Regulatory Harmonisation (AMRH) Initiative was formed in 2009 and subsequently, three regional initiatives (East African Community Medicines Regulatory Harmonisation [MRH], Southern African Development Community [SADC]/ZaZiBoNa MRH, and the Economic Community of West Africa States MRH) were established. As these initiatives serve as a foundation for the African Medicines Agency (AMA), the aim of this study was to compare their operating models, successes and challenges to identify opportunities for improvement and alignment. Methods: A mixed method approach was used for the data collection using a questionnaire, the Process, Effectiveness and Efficiency Rating (PEER), developed by the authors specifically for this study and semi-structured interview techniques. There were 23 study participants (one from each agency of the member countries of the three regions). It was hoped that data generated from this study would lead to a series of recommendations, which would then be ratified by the regulatory authorities. Results: Most respondents stated that AMRH contributed to the strengthening of regulatory systems and harmonising regulatory requirements across economic regions of Africa, potentially resulting in improved access to quality-assured medicines. Although established at different times and at the discretion of each region, the marketing authorisation application review processes are largely similar, with a few differences noted in the eligibility and submission requirements, type of procedures employed, the timelines and fees payable. The challenges identified in the three regions are also similar, with the most noteworthy being the lack of a binding legal framework for regional approvals. Conclusion: In this study, we compared the process, successes and challenges of these three regional harmonisation initiatives in Africa addressing the areas of legal frameworks, information management systems, the accessibility and affordability of medicines and reliance that will bring greater alignment and efficiency in their operating models, thereby strengthening the foundation of the soon-to-be-operationalised AMA.
... According to Sithole et al. (16), authorities in the Southern African Development Community (SADC) region require the submission of the dossier in CTD format; however, there are some country-specific requirements, such as bioequivalence, labeling and local Quality Information Summary (QIS) and Quality Overall Summary (QOS), that still impede harmonization efforts. This is consistent with findings from other studies in the literature (2,17). Researchers conclude that there is a need for countries to make a deliberate effort to review their legislation to adopt provisions that facilitate the harmonization of the registration and labeling requirements for medicinal products in this region (16). ...
Article
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Regulatory harmonization and convergence have been identified as the key driver in promoting efficient evaluation of medicines, reducing workload, and supporting earlier access to medicines on the African continent. There has been great progress to date in enhancing regulatory harmonization and convergence on the African continent via the Regional Economic Communities (RECs) and with the establishment of the Africa Medicines Agency (AMA). In this article, the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) Africa Regulatory Network (ARN) presents its perspective based on the available literature review and results from a survey conducted with innovative biopharmaceutical companies to gather experiences using regional joint assessment procedures (JAPs) in Africa, such as the East African Community Medicines Regulatory Harmonization (EAC-MRH), the West African Medicines Regulatory Harmonization (WA-MRH), and the Southern African Development Community Medicines Regulatory Harmonization (SADC-MRH) initiative through the ZAZIBONA Collaborative Procedure for Medicines Registration (ZaZiBoNa), and provides best practices in this evolving landscape. The article also assesses other collaborative registration pathways available to facilitating registration of pharmaceutical products in African countries, such as WHO Collaborative Registration Procedures (CRP), Swissmedic’s Marketing Authorisation for Global Health Products (MAGHP) and EU Medicines for All (EU-M4ALL). Benefits and challenges of each of the existing pathways are discussed in this article. Main benefits include building more expert capacity and improved collaboration amongst experts, as well as shorter review timelines in some cases. Key challenges include the lack of predictability in the adherence to procedural timelines as defined per guidelines, lengthy timeline to achieve national marketing authorization following joint assessment, the lack of dedicated personnel, administrative issues during the submission process as well as additional country-specific requirements on top of JAP-specific requirements. Our recommendations for improvements include harmonization of requirements across countries and regions and with international standards, appropriate resource allocation for JAP activities to ensure adherence to timelines, use of JAPs throughout the entire product lifecycle and all product categories, adequate use of digital technologies, and improved communication and transparency with applicants. These improvements will allow industry to better plan their filing strategies for the region which will lead to overall improved usability of the JAPs in Africa and enable faster patient access.
... The AMRH initiative's goal was for NRAs within each of Africa's regional economic communities (RECs) to address this problem by coordinating their activities, relying on the work of one another and other trusted regulatory authorities, and applying other principles of smart regulation [5]. Specifically, NRAs within an REC would harmonize technical requirements and standards for medical products regulation, perform joint reviews of marketing authorization applications and joint inspections of manufacturing sites, and increase the use of reliance and cooperation in regulatory matters related to medical products [3,[6][7][8][9]. The resulting improvements in regulatory efficiency would make it easier and faster for medicines manufacturers to register quality products [3,10]. ...
Article
Full-text available
In the African Medicines Regulatory Harmonization initiative, national regulatory authorities (NRAs) within each of Africa’s regional economic communities coordinate their activities, rely on the work of one another and other trusted regulatory authorities, and apply other principles of smart regulation. The first regional medicines regulatory harmonization (MRH) initiative in Africa was launched in 2012, with the goal of accelerating access to quality, safe, effective medical products, and now five MRH initiatives are active on the continent. Thus, a wealth of knowledge regarding best practices and approaches to dealing with common challenges has accumulated. The goal of this qualitative study was to gather and share information on these best practices. To do this, we conducted interviews with key participants from four regional MRH initiatives—the East African Community (EAC), Southern African Development Community (SADC), Economic Community of West African States (ECOWAS), and Intergovernmental Authority on Development (IGAD)—as well as representatives from the pharmaceutical industry. Here we explore major themes that emerged from the interviews: 1. Transparency and reliability are critical; 2. Reliance is essential for smart regulation; 3. Multiple successful strategies for NRA capacity building have been identified; 4. Communication between heads of agencies is essential; 5. Cooperation at the regional level is not possible without leadership at the NRA level; 6. Sustainable funding remains challenging; and 7. Industry has important insights. We hope that the information on best practices shared in this article can benefit regional MRH initiatives inside and outside of Africa, ultimately helping them accelerate access to quality, safe, effective medical products.
... Regional work sharing is therefore encouraged and one such initiative is the ZaZiBoNa work sharing initiative in South Africa (20,21). Regulatory agencies participating in this initiative therefore cooperate in the assessment of applications for registration of medicines (22,23). ...
Article
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Background Medical products incorporating nanoparticle drug delivery systems (nanomedicines) are therapeutic or imaging agents, which comprise a delivery system within the nanometer size range (1 – 1000 nm). As medical products, nanomedicines meet definitions of medicines according to various national legislations for regulation of medicines. However, for the regulation of nanomedicines, additional assessments including toxicological issues have to be considered. These complexities require extra regulatory effort. In the resource-limited context of low- and middle-income countries, many National Medicines Regulatory Authorities (NMRAs) lack resources and capacities to effectively assure the quality of medicinal products in their countries. With emerging trends in innovative technologies, including nanotechnology, this burden is worsened. The need to overcome regulatory challenges drove the formation of a work sharing initiative in the Southern African Development Community (SADC), ZaZiBoNA in 2013. Regulatory agencies participating in this initiative cooperate in the assessment of applications for registration of medicines. Methods A cross-sectional exploratory study design with qualitative techniques was used to investigate the status of the regulation of nanomedicines in Southern African countries in particular those participating in the ZaZiBoNA initiative. Results The study found that in general, NMRAs are aware of the existence of nanomedicines and they apply legislation applicable to other medical products. The NMRAs however neither have specific definition for nanomedicines and technical guidance documents, nor technical committees specific for consideration of nanomedicines. Collaboration with external experts or organisations in the regulation of nanomedicines was also found to be lacking. Discussion Capacity building and collaboration in the area of regulation of nanomedicines is strongly encouraged.
... To address the challenges of a globalised market while navigating through complex supply chains, NRAs are focusing on making the best use of the available human and financial resources; however, major disparities in the regulatory capacity of NRAs exist between low-and high-income countries [2,3]. According to the World Health Organization (WHO), almost 30% of NRAs do not have the adequate expertise, quality management systems, or necessary resources to undertake core regulatory functions [4]. ...
Article
Background: Despite the worldwide need for increased access to safe and effective medicines, there is a lack of innovative medicines in many low- to middle-income countries. On the African continent, this is partly due to capacity limitations of National Regulatory Authorities (NRAs). One important approach to address this issue is work sharing and regulatory reliance. Therefore, the aim of this study of regulatory authorities on the African continent was to identify which risk-based approaches are being used as well as their foreseen role in the future. Methods: The study employed a questionnaire to identify which risk-based models are used for the regulatory approval of medicines and to determine which frameworks are in place to enable a risk-based approach, as well as to provide insight into the future direction for risk-based models. The questionnaire was sent electronically to 26 NRAs in the African Continent. Results: Twenty-one authorities (80%) completed the questionnaire. Work sharing was the most commonly used model, followed closely by unilaterial reliance, information sharing, and collaborative review. These methods were perceived to be an effective and efficient use of resources, enabling faster medicine availability for patients. The unilateral reliance approach by the authorities included abridged (85%), verification (70%) and recognition (50%) models for a range of products. However, challenges included a lack of guidelines to undertake a reliance review together with resource constraints, while access to assessment reports was the most common barrier to using a unilateral reliance model. Conclusions: Many authorities in Africa have adopted a risk-based approach to medicines registration and created work sharing, unilateral reliance pathways and regionalisation models to facilitate the availability of medicines. The authorities believe that in future, assessment routes should move from stand-alone reviews to risk-based models. However, this study indicated that there would be challenges to implement this approach in practice, which would include improving resource capacity and the number of expert reviewers as well as implementing electronic tracking systems.
... This is particularly important in low and low-middle-income countries where there can be considerable supply and access issues, e.g., Uganda. • Strengthen prevention and detection of counterfeit/sub-standard antibiotics: This can be achieved through regional collaborative initiatives for capacity-building of regulatory authorities to enhance Good Manufacturing Practice (GMP), quality assurance, pharmacovigilance, and law enforcement, e.g., ZaZiBoNA which is an initiative among the SADC countries [222]. This builds on the recent WHO Lomé initiative [223]. ...
Article
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There are serious concerns with rising antimicrobial resistance (AMR) across countries increasing morbidity, mortality and costs. These concerns have resulted in a plethora of initiatives globally and nationally including national action plans (NAPs) to reduce AMR. Africa is no exception, especially with the highest rates of AMR globally. Key activities in NAPs include gaining a greater understanding of current antimicrobial utilization patterns through point prevalence surveys (PPS) and subsequently instigating antimicrobial stewardship programs (ASPs). Consequently, there is a need to comprehensively document current utilization patterns among hospitals across Africa coupled with ASP studies. In total, 33 PPS studies ranging from single up to 18 hospitals were documented from a narrative review with typically over 50% of in-patients prescribed antimicrobials, up to 97.6% in Nigeria. The penicillins, ceftriaxone and metronidazole, were the most prescribed antibiotics. Appreciable extended prescribing of antibiotics up to 6 days or more post-operatively was seen across Africa to prevent surgical site infections. At least 19 ASPs have been instigated across Africa in recent years to improve future prescribing utilizing a range of prescribing indicators. The various findings resulted in a range of suggested activities that key stakeholders, including governments and healthcare professionals, should undertake in the short, medium and long term to improve future antimicrobial prescribing and reduce AMR across Africa.
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Introduction The COVID-19 pandemic highlighted an urgent need for harmonised requirements for the regulation of medicines. To fully implement harmonised medicines regulations across Africa, common technical standards of medicine regulations are needed. One such technical standard is the labelling of medicines on outer packaging. In this study, we compared outer packaging labelling requirements and transition terms for harmonization for countries in the Southern African Development Community (SADC) region. Methods Data on legislation and/or regulatory guidelines for medicine outer packaging labelling from National Medicines Regulatory Authorities (NMRAs) were obtained for countries in the SADC region (n = 16) by February 2023. A detailed comparative content analysis was conducted to determine alignment with the requirements of the Southern African Development Community (SADC) harmonised labelling guidelines to assess readiness levels of each country to transition to the SADC harmonised labelling guideline for outer packaging of medicines. Results Content analysis showed at least 11 out of 16 countries require national legal reform to transition to the SADC harmonised labelling guideline. In all cases where countries specified labelling requirements for outer packaging of medicines, these were stipulated in national medicines legislation. Conclusion Even though there is a high level of alignment across the countries in terms of national labelling requirements, most countries in the SADC region would still require national legislative reform to transition to regional harmonised labelling requirements and then ultimately to continental requirements of the African Medicines Agency (AMA).
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The global burden of HIV remains unacceptably high despite significant progress made in HIV treatment and prevention. There is an urgent need to scale up the comprehensive HIV prevention strategies that include pre-exposure prophylaxis (PrEP). Oral PrEP is highly effective in preventing HIV acquisition when taken regularly, but this remains a challenge for some at-risk individuals. Therefore, there is a need for other HIV prevention options. The dapivirine vaginal ring (DVR) and long-acting injectable cabotegravir (CAB-LA) are novel biomedical interventions that are safe and efficacious for HIV pre-exposure prophylaxis, as demonstrated in recently completed clinical trials. Timely roll-out and scalability of efficacious interventions depend on the registration process with the national medicine regulatory authorities (NMRAs). The Medicines Control Authority of Zimbabwe (MCAZ) was the first NMRA globally to approve the DVR in July 2021 and the first in Africa to approve CAB-LA for HIV prevention in July 2022. The regulatory review process for DVR and CAB-LA by MCAZ took 4.5 and 5.5 months, respectively. This efficient review process of the two interventions by MCAZ, a regulatory body in a resource-limited setting, provides important lessons to shorten timelines between the completion of the clinical development process and the registration of essential medicines.
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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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Introduction: Regulatory reliance, harmonization and work sharing have grown over the last few years, resulting in greater sharing of work and information among regulators, enabling efficient use of limited resources and preventing duplication of work. Various initiatives on the African continent include ZaZiBoNa, the Southern African Development Community (SADC) collaborative medicines registration initiative. ZaZiBoNa has resulted in great savings in time and resources; however, identified challenges include lack of clear information regarding the participating countries registration processes and requirements as well as lengthy registration times. The aim of this study, therefore, was to compare the data requirements and review models employed in the assessment of applications for registration, the target timelines for key milestones and the metrics of applications received and approved in 2019 and 2020 by Mozambique, Namibia, South Africa, Tanzania, Zambia, and Zimbabwe. Methods: A senior member of the division responsible for issuing marketing authorisations completed an established and validated questionnaire, which standardizes 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 majority of applications received and approved by all six agencies in 2019 and 2020 were for generics. The mean approval times for generics varied across the countries, with ranges of 218–890 calendar days in 2019 and 158–696 calendar days in 2020. All three types of scientific assessment review models were used by the six agencies and data requirements and extent of scientific assessment were similar for five countries, while one conducted full reviews for new active substances. A large variation was observed in the targets set by the six agencies for the different milestones as well as overall approval times. Conclusions: The study identified the strengths of the countries as well as opportunities for improvement and alignment. Implementation of the recommendations made as in this study will enhance the countries' individual systems, enabling them to efficiently support the ZaZiBoNa initiative.
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Purpose The aims of this study were to assess the current regulatory review process of the Medicines Control Authority of Zimbabwe (MCAZ), identify key milestones and target timelines, evaluate the overall performance from 2017 to 2019, identify good review practices, evaluate the quality of decision-making processes, and identify the challenges and opportunities for improvement. Methods A questionnaire was completed by the MCAZ. The agency has participated in the Optimising Efficiencies in Regulatory Agencies (OpERA) program, a multinational endeavor to characterize assessment procedures and metrics associated with regulatory agencies and regional regulatory initiatives. Data identifying the milestones and overall approval times for all products registered MCAZ from 2017 to 2019 were collected and analyzed. Results The MCAZ conducts a full review of quality, safety, and efficacy data for generics and biosimilars not approved by a reference agency, an abridged review for products approved by a reference agency and a verification review for World Health Organization prequalified products under the collaborative registration procedure. The highest number of reviewed products is generics manufactured by foreign companies. There has been an improvement in review times for all categories of products over the three-year period. Guidelines, standard operating procedures, and review templates are in place and the majority of indicators for good review practices are implemented. Although quality decision-making practices are implemented, there is no formal framework in place. Conclusion The MCAZ successfully implements three types of review models in line with international standards. Overall, target timelines are realistic and what is achievable with the current available resources. Recommendations made such as the review of available human resources, separation of agency and company time when setting and measuring targets, review of the templates and benefit-risk framework used for abridged review, and development of a decision-making framework present opportunities for an enhanced regulatory review process.
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The Southern African Development Community (SADC) collaborative medicines registration initiative ZaZiBoNa is a successful regional work-sharing initiative on the African continent. This paper reviews the history of the ZaZiBoNa initiative, reflects on what has been realized in six years of operation and what still needs to be achieved. Statistics for the work done by the initiative are available in the literature, but there has not been a critical review of the process, including an analysis of factors contributing to the success of the initiative and conversely those negatively affecting performance. To do this, publicly available literature and statistics, meeting records, terms of reference and unpublished documents belonging to the initiative were reviewed. The successes of the ZaZiBoNa initiative can be attributed to leadership commitment, a clear vision and governance structure providing direction, and a clear, documented operating model, processes and objectives defined from the onset of the initiative. Closure of the gaps that were identified and implementation of the recommendations that were made in this paper will further strengthen the initiative. Furthermore, other regional harmonization or work-sharing initiatives on the African continent and beyond can draw lessons from this review of the ZaZiBoNa initiative for improved efficiency and effectiveness.
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Access to essential medicines is a key pillar of any health system seeking to deliver universal health coverage. Science-based, independent regulation of medical products is a critical part of ensuring that only quality essential medicines reach the patients who need them. • In this article, we explore the progress the East African Community's Medicines Regulatory Harmonization (EAC MRH) initiative, launched in 2012, has made toward its goal of improving access to essential medicines. The initiative's initial focus was on registering generic medicines, with a plan to expand to other classes of medical products, as well as to other regulatory functions. • From 2012 to 2017, the timeline for national assessments of medicinal product applications decreased from roughly 24 months to 8-14 months, if products were assessed through the new joint assessment process (involving 2 or more national medicines regulatory authorities). • Since 2015, the initiative has conducted 10 joint product assessment sessions in which 83 medicinal product applications were considered, resulting in the recommendation of 36 products for registration by EAC Partner States. • Overall, the median timeline for a joint assessment, from submission of the application through final decision, has been a little over a year (372 days); 170 of these days represent time used by manufacturers to answer queries. However, the median timeline for a joint assessment in 2019 was only 240 days, indicating that the process has become more efficient. • Shifting from relying on donor support to becoming self-sustaining remains a challenge for the EAC MRH initiative.
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Background: The aims of this study were to assess the regulatory review process in South Africa from 2015 to 2017, identify the key milestones and timelines; evaluate the effectiveness of measures to ensure consistency, transparency, timeliness, and predictability in the review process; and to provide recommendations for enhanced regulatory practices. Methods: A questionnaire was completed by the Medicines Control Council (MCC) to describe the organization of the authority, record key milestones and timelines in the review process and to identify good review practices (GRevPs). Results: Currently, the MCC conducts a full assessment of quality, efficacy, and safety data in the review of all applications. The overall regulatory median approval time decreased by 14% in 2017 (1411 calendar days) compared with that of 2016, despite the 27% increase in the number of applications. However, the MCC has no target for overall approval time of new active substance applications and no targets for key review milestones. Guidelines, standard operating procedures, and review templates are in place, while the formal implementation of GRevPs and the application of an electronic document management system are planned for the near future. Conclusions: As the MCC transitions to the newly established South Africa Health Products Regulatory Authority, it would be crucial for the authority to recognize the opportunities for an enhanced regulatory review and should consider models such as abridged assessment, which encompass elements of risk stratification and reliance. It is hoped that resource constraints may then be alleviated and capacity developed to meet target timelines.
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