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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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Frontiers in Medicine | www.frontiersin.org 9April 2022 | Volume 9 | Article 898743
... 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). ...
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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.
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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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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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Background Timely access to new medicines may be addressed through strengthening of registration efficiencies and timelines by establishing and refining value-added registration processes, resources, and systems. The aims of this study were to evaluate the timelines of the milestones of the South African review process and the overall approval process for new active substances (NASs) in 2015–2018 and to provide recommendations for improved patients’ access to new medicines through timely registration.Methods Data identifying the milestones and overall approval times for NASs registered by the South African Agency during 2015–2018 were collected and analyzed.ResultsThe most NASs (42) were approved in 2017 and the least (15) in 2018. The shortest median approval time (1218 calendar days) was achieved in 2015 and the longest (2124 days), in 2018. All applications were reviewed using the full review process, and 16/99 (16%) were assigned priority status and were reviewed and approved through the fast track review.Conclusions While the extensive delays in NASs approvals in South Africa may be attributed to inefficient operational processes, resource constraints, and as an increased number of applications for registration, the newly established South African Heath Products Regulatory Agency has re-engineered and streamlined its regulatory review process, which has been piloted and will be enhanced prior to final implementation. Among recommendations for improvement, SAHPRA should consider measurement and monitoring of milestones, facilitated regulatory pathways, implementing a reliance strategy, and a quality management system.
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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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The European Union is a confederation of 28 member states that are located in Europe. A single market system has been developed in European Union by the laws, this leads to completely different type of procedures for entering into EU market. European regulation has established and harmonized many aspects of regulating the production, distribution, and use of medicines in the EU. This article discusses the ways and procedures for entering into one of the world’s prestigious market. It also describes about the post authorization steps and applications along with fees for obtaining different types of marketing authorization in EU.