ArticlePDF Available

Evaluation of the Regulatory Review Process in Zimbabwe: Challenges and Opportunities

Authors:
Article

Evaluation of the Regulatory Review Process in Zimbabwe: Challenges and Opportunities

Abstract and Figures

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.
Content may be subject to copyright.
Vol:.(1234567890)
Therapeutic Innovation & Regulatory Science (2021) 55:474–489
https://doi.org/10.1007/s43441-020-00242-z
1 3
ORIGINAL RESEARCH
Evaluation oftheRegulatory Review Process inZimbabwe: Challenges
andOpportunities
TariroSithole1,2· GuguMahlangu2· SamSalek1,4· StuartWalker1,3
Received: 14 August 2020 / Accepted: 10 November 2020 / Published online: 2 January 2021
© The Author(s) 2021
Abstract
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 oppor-
tunities for improvement.
Methods A questionnaire was completed by the MCAZ. The agency has participated in the Optimising Efficiencies in Regu-
latory 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 imple-
mented, 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.
Keywords Medicine control authority of Zimbabwe (MCAZ)· International best practice· Regulatory review models·
Good review practices· Timelines· Good decision-making practice
Abbreviations
AU African Union
AUC African Union Commission
AUDA NEPAD African Union Development
Agency New Partnership for Africa
Development
AMRH African Medicines Regulatory
Harmonisation
CIRS Centre for Innovation in Regulatory
Science
CPP Certificate of Pharmaceutical Product
CRP Collaborative medicines registration
procedure
GBT Global Benchmarking Tool
GMP Good manufacturing practice
GRevP Good review practices
* Stuart Walker
drstuartwalker@me.com
1 School ofLife andMedical Sciences, University
ofHertfordshire, Hatfield, UK
2 Medicines Control Authority ofZimbabwe, Harare,
Zimbabwe
3 Centre forInnovation inRegulatory Science, 160 Blackfriars
Road, LondonSE18EZ, UK
4 Institute ofMedicines Development, Cardiff, UK
475Therapeutic Innovation & Regulatory Science (2021) 55:474–489
1 3
ICH International Council for Harmonisation
of Technical Requirements for Pharma-
ceuticals for Human Use
LMICs Low- and middle-income countries
MASCA Medicines and Allied Substances Con-
trol Act
MCAZ Medicines Control Authority of
Zimbabwe
MHRA Medicines and Healthcare Products
Regulatory Authority
MRH Medicines registration harmonization
NRA National regulatory agency
NCEs New chemical entities
OpERA OptimisingEfficiencies in Regulatory
Agencies
PMPA Pharmaceutical Manufacturing Plan for
Africa
QMS Quality management systems
RCORE Regional centre of regulatory excellence
SADC Southern African Development
Community
SOPs Standard operating procedures
SRAs Stringent regulatory authorities
SmPC Summary of product characteristics
WHO World Health Organization
Introduction
Zimbabwe andtheNational Medicines Regulatory
Authority
Zimbabwe is a landlocked country with a gross domes-
tic product (GDP) of 31 billion USD and a population of
14.5 million in 2018 [1]. The country is bordered by South
Africa, Namibia, Zambia, Botswana, and Mozambique [2].
Regulation of medicines began in 1969 through an Act of
Parliament, the Drugs and Allied Substances Control Act of
1969 (Chapter15.03) [3]. The Medicines and Allied Sub-
stances Control Act was promulgated in 1997, creating an
autonomous agency independent of the fiscus, the Medicines
Control Authority of Zimbabwe (MCAZ). The MCAZ’s
chemistry laboratory is prequalified by the World Health
Organization [4]. The MCAZ has a robust quality manage-
ment system, which resulted in the ISO 9001 certification
by the Standards Association of Zimbabwe in 2019 [5]. The
MCAZ offers training to regulators on the continent and as
a result is designated as a Regional Centre of Regulatory
Excellence (RCORE) for medicines evaluation and registra-
tion, clinical trials authorization, and quality assurance and
control by the African Union’s Development Agency New
Partnership for Africa Development (AUDA – NEPAD)
[6]. In addition, theMCAZ is a founding member of the
ZAZIBONA collaborative medicines registration initiative
and also responsible for coordinating the Southern African
Development Community (SADC) Medicines Registration
Harmonization (MRH) project as the implementing agency
[7]. The project aims to build the regulatory capacity of
member states in various areas including supporting agen-
cies to be assessed using the WHO Global Benchmarking
Tool and to implement measures to address the gaps that
have been identified.
WHO Assessment ofRegulatory Authorities
Various countries or jurisdictions have legislation mandat-
ing the regulation of medical products to ensure quality,
safety, and efficacy [8]. The capacity to regulate medical
products varies widely and traditionally, and countries that
were members or observers of the International Council for
Harmonisation of Technical Requirements for Pharmaceu-
ticals for Human Use (ICH) were regarded as having strin-
gent regulatory authorities (SRAs) [9]. However, the World
Health Organization (WHO) has recently made a proposal
to use the term WHO-listed authorities (maturity level 4)
for authorities previously referred to as SRA and award-
listed authority status to any additional authorities based on
the Global Benchmarking Tool (GBTs) [9, 10]. This tool
allows for the objective evaluation of national regulatory
systems, as agreed by WHO Member states in the World
Health Assembly Resolution 67.20 on Regulatory System
Strengthening for medical products [11]. The GBT evalu-
ates the overarching national regulatory system as well as
the following functions that make up the regulatory system:
registration and marketing authorization, market surveil-
lance and control, regulatory inspection, vigilance, licensing
establishments, clinical trial oversight, laboratory testing,
and NRA lot release [10]. The WHO has begun the process
of evaluating the regulatory systems of countries includ-
ing low- and middle-income countries (LMICs). One of the
outcomes of the assessments using the GBT is the develop-
ment of an Institutional Development Plan, which identi-
fies gaps as well as the activities and resources required to
strengthen the regulatory system. As of May 2020, of the 55
countries in Africa, the WHO had benchmarked the national
medicines regulatory agencies of 13 while 34 had conducted
self-benchmarking, a pre-requisite for formal benchmarking
by the WHO [12]. Tanzania and Ghana were benchmarked
and attained maturity level 3 status which represents “a sta-
ble, well-functioning and integrated regulatory system” [9,
13, 14]. Regulatory reviews fall under the registration and
marketing authorization function of the GBT.
Unlike high-income countries, there is limited informa-
tion in the public domain on the regulatory review/assess-
ment systems and performance of LMIC [15]. Evaluation of
the regulatory review systems of a number of high-income
476 Therapeutic Innovation & Regulatory Science (2021) 55:474–489
1 3
and upper middle-income countries, for example, Saudi Ara-
bia, Jordan, Turkey, and South Africa, are available in the
literature [1620]. However, it appears that there are few
published assessments of the regulatory review systems in
LMIC in Africa. The aim of this study was, therefore, to
evaluate the current regulatory review process in Zimba-
bwe, identifying challenges and opportunities for growth and
improvement.
Study Objectives
The main objectives of this exploratory study were to:
1. Assessthe current regulatory review process in Zimba-
bwe,
2. Identifythe key milestones and target timelines in the
review process,
3. Evaluatethe overall performance for the review models
and different product types approved in Zimbabwe dur-
ing the period 2017 to 2019,
4. Evaluatehow the quality of the process of decision mak-
ing is built into the regulatory review process and regis-
tration of medicines, and
5. Identify the challenges and opportunities for an
enhanced regulatory process in Zimbabwe, with a view
to expediting patients’ access to life-saving medicines.
Methods
Ethical Approval
The authors’ institutions do not require ethics approval for
the type of study reported here.
Study Rationale
The study was planned as part of continuous improvement
efforts of the agency as it was deemed important to identify
the challenges and opportunities.
Data Collection Process
A questionnaire technique [21] was used to identify the key
milestones and activities associated with the review pro-
cesses and practices within the MCAZ. The questionnaire
was initially completed by a senior assessor, reviewed by the
division’s management and verified by the Director General
in 2019. To aid agencies who achieve the goals of regula-
tory efficiency, the Centre for Innovation in Regulatory Sci-
ence (CIRS) developed a uniqueregulatory-strengthening
tool entitled OptimisingEfficiencies in Regulatory Agencies
(OpERA). The OpERA project was initiated in 2013 based
on requests from regulatory agencies, and the objectives
of this programare to provide benchmarking data that can
be used to define performance targets and focus ongoing
performance improvement initiatives; accurately compare
the processes used in the review of new medicines market-
ing authorizations; encourage the sharing of information on
common practices in order to learn from others’ experiences;
and encourage the systematic measuring of the processes
that occur during the review of new medicines marketing
authorization [22].
The questionnaire consists of 5 parts [21, 22].
Part 1: Organization of the agency documents the infor-
mation on the structure, organization, and resources of the
agency.
Part 2: Types of review models identify different types
of review model(s) used for the scientific assessment of
medicines in terms of the data assessed and level of detail
by the agency, as well as how the agency might rely on the
results of assessments and reviews carried out by a refer-
ence agency.
Part 3: Key milestones in the review process document
information on the key milestone dates, using the online
OpERA tool and map the process of assessment starting
from receipt of the dossier, validation/screening, the num-
ber of cycles of scientific assessments including the ques-
tions to the sponsor/applicant and expert registration com-
mittee meetings to the final decision on approval or refusal
of a product for registration. A standardized process map
embedded in the questionnaire was based on the experience
of studying established and emerging regulatory authori-
ties. Data were collected for new chemical entities (NCEs),
biologicals, and biosimilars, and generics registered by the
Zimbabwean NRA during the period 2017–2019. These data
were sourced directly from the division within the authority
responsible for the regulatory review process.
Part 4: Good review practices (GRevP) evaluate how
quality is built into the regulatory process by examining
activities that have been adopted to improve consistency,
transparency, timeliness, and competency in the review
process.
Part 5: Quality decision-making processes explore the
quality of agency decision-making practices and whether
measures are in place to ensure that quality decisions are
made around the data during the registration process.
Models ofRegulatory Review
There are three models for the scientific regulatory review
of a product that can be used by regulatory authorities [21]
and these are as follows:
477Therapeutic Innovation & Regulatory Science (2021) 55:474–489
1 3
(i) The verification review (type 1), which requires prior
approval of a product by two or more reference or
competent regulatory authorities allowing the agency
relying on such assessments to employ a verification
process to validate a product and ensure that it con-
forms to the previously authorized product specifica-
tions.
(ii) The abridged review (type 2), which involves an
abridged evaluation of a medicine taking into con-
sideration local factors and environment, with the
pre-requisite of registration by at least one reference
or competent regulatory authority.
(iii) The full review, type 3A, which involves the agency
carrying out a full review of quality, safety, and effi-
cacy, but requires that the product has previously
been reviewed by an agency for which there is a CPP
or type 3B which involves an independent assessment
of a product’s quality, pre-clinical, as well as clinical
safety and efficacy, but which has not been evaluated
by any previous agency.
Results
The results will be presented under five major headings:
(Part I) organization of the agency (this section addresses
objectives 1 and 5); (Part II) types of review models used in
Zimbabwe (this section addresses objectives 1 and 5); (Part
III) key milestones in the Zimbabwe Regulatory review pro-
cess (this section addresses objectives 1, 2, 3, and 5; (Part
IV) good review practices: building quality into the regula-
tory process (this section addresses objectives 1, 4, and 5);
and (Part V) quality decision-making practices (this section
of the results addresses objectives 1, 4, and 5).
Part 1: Organization oftheAgency
The MCAZ is an autonomous agency established in 1997
as a successor to the Drugs Control Council and the Zim-
babwe Regional Quality Control Laboratory. The MCAZ
regulates medicinal products for human and veterinary use
as well as medical devices and diagnostics. The scope of
control of medical devices is currently limited to gloves and
condoms but will increase once the medical devices’ regula-
tions, which have been developed, are approved. The MCAZ
scope of activities includes issuing of marketing authoriza-
tions/product licenses, post-marketing surveillance, labora-
tory analysis of samples, clinical trial authorization, regula-
tion of advertising, site inspections/visits, import and export
control, and licensing of premises and persons responsible
for the manufacture, supply, distribution, storage, and sale
of medicines.
The MCAZ currently has 143 full-time personnel includ-
ing management, technical, and administrative staff. Eight-
een full-time reviewers are dedicated to assess applications
for marketing authorization/product licenses for synthetic
and biological products, of whom 3 specialize in the review
of biological products. As the MCAZ does not receive many
applications for registration of biological products, the 3
reviewers also assess chemical/synthetic products (small
molecules). The majority of the staff reviewing marketing
authorization applications are pharmacists and some of them
have post-graduate qualifications. However, no physicians
are engaged in the regulatory review process for issuing mar-
keting authorizations.
Part 2: Types ofReview Models Used inZimbabwe
The MCAZ carries out all three types of established reg-
ulatory review [21], although there is some difference in
the requirement of the number of approvals by a reference
agency.
The verification (type 1) review is used only for WHO-
prequalified (PQ) products through the WHO Collaborative
Medicines Registration Procedure (CRP), typically foreign
generic medicines [23]. This type of review is enabled
because WHO shares unredacted assessment reports for PQ
products with the manufacturer’s consent and WHO GMP
inspection outcomes are also available. Reviews involve
ensuring that the product approved by the WHO PQ is the
same as that submitted to MCAZ and reviewing country-spe-
cific requirements such as labeling. Post-approval changes
are communicated to the MCAZ by WHO PQ. The target
timeline for this route is 90 calendar days (Table1).
The abridged (type 2) review is used for products
approved by at least one reference authority; for example,
the European Medicines Agency, Medicines and Healthcare
Table 1. Target Timelines for the MCAZ Review Process
Milestone/process Target
Acknowledgement of receipt 30 calendar days
Screening/validation 60 calendar days
Acknowledgement/screening/validation 90 calendar days
Scientific assessment (per review cycle) 60 calendar days
Sponsor response time (per review cycle) 60 calendar days
Scientific assessment/sponsor response 120 calendar days
Expert Committee procedure No target time
Authorization procedure 60 calendar days
Full review 480 calendar days
Abridged review 270 calendar days
Verification review (WHO CRP) 90 calendar days
Expedited review/fast track 180 calendar days
ZAZIBONA review 270 calendar days
478 Therapeutic Innovation & Regulatory Science (2021) 55:474–489
1 3
Products Regulatory Authority, United States Food Drug
Administration, Australian Therapeutic Goods Administra-
tion, Health Canada, Japanese Pharmaceuticals and Medi-
cal Devices Agency, and other mature agencies in Europe.
This is the primary route for NCEs and biologicals. Generics
and biosimilars approved by a reference agency will also
go through the abridged route. However, the MCAZ does
not have any formal agreements in place with any of these
reference agencies to facilitate sharing of unredacted assess-
ment reports; therefore, public assessment reports are used
instead. The target timeline for this route is 270 calendar
days (Table1).
A full review (type 3A) of quality, safety, and efficacy
is conducted for products not approved by any reference
agency, and these products are usually generics and biosimi-
lars. For generics, the chemistry, manufacturing and control
(CMC), and bioequivalence are reviewed sequentially while
for biosimilars the quality, non-clinical and clinical data are
reviewed in parallel. The target timeline for this route is 480
calendar days (Table1). ZaZiBoNa products undergo a full
review; however, they are placed in their own queue with a
target timeline of 270days. A type 3B review which involves
an independent assessment of pre-clinical (safety) and clini-
cal (efficacy) data is not conducted.
An expedited/fast-track review is also conducted. Appli-
cations are placed at the front of the queue but can be
assessed using any of the above types of review (1, 2, or 3)
depending on the product. Applications from local manu-
facturing companies and products for unmet medical needs
are also given a priority review. The target timeline for this
route is 180 calendar days (Table1).
Data Requirements andAssessment
At present, the Certificate of Pharmaceutical Product (CPP)
is legally required for registration in Zimbabwe for all three
review types, as this is used as evidence of registration in
the country of origin and to confirm similarity of the product
being submitted to Zimbabwe with the one that is approved
in the country of origin. The requirement for the CPP may
be waived at the time of submission of the application, but
the CPP must be submitted prior to registration. Evidence of
compliance with good manufacturing practices (GMP) for
both the active pharmaceutical ingredient and finished phar-
maceutical product manufacturers, product samples, copies
of the labeling, and a full dossier (modules 1–5) is required
for all review types. A detailed assessment of the data is car-
ried out, and the relevant assessment reports are prepared.
The MCAZ performs benefit-risk assessments during the
abridged review of NCEs and biologicals, as well as during
a full review of biosimilars taking into account differences
in medical culture/practice, ethnic factors, national disease
patterns, and unmet medical needs. As previously stated, the
authority does not access internal assessment reports from
other authorities except from the WHO through the collabo-
rative registration procedure. However, publicly available
reports such as European Public Assessment Reports and
those from other reference/recognized agencies are used dur-
ing the review process.
Part 3: Key Milestones intheZimbabwe Regulatory
Review Process
The regulatory review process and authorization of medi-
cines are performed within the Evaluations and Registration
division of the MCAZ, and this is depicted in Fig.1 includ-
ing milestones and timelines. This is a simplified representa-
tion of the main steps in the review of applications. The map
represents the review and authorization of a product that
goes to approval after one review cycle. In reality, it often
takes a minimum of three review cycles before the review of
a product is finalized. In addition, the map does not include
steps such as the submission of representations to the admin-
istrative court within a specified period to appeal against the
refusal of an application.
Receipt andValidation Procedures
All applications for registration are received by the Admin-
istrative Regulatory Officer and tabled before the Registra-
tion Committee. The target is to send an acknowledgement
of receipt of the application by the committee within 30
calendar days from the date of receipt. Applications are then
screened/validated and the target time for completion of this
step is 90 calendar days from the date of receipt of the appli-
cation. Products that fail screening are removed from the
queue and applicant requested to provide the missing infor-
mation. Products that pass screening are placed in a queue
awaiting allocation to the next available assessor. The target
time for start of the scientific assessment is 180 calendar
days from the date of receipt of the application. All product
types join the same queue and are assessed following the
“first in first out” principle, regardless of the nature of the
product or the review type, with the exception of expedited/
fast-track review applications.
Scientific Assessment
The start of the scientific assessment is formally recorded.
Scientific data are separated into quality, safety, and efficacy
for review, and these are assessed sequentially by one asses-
sor when it is a generic medicine. However, the sections may
also be assessed in parallel by different assessors when it is
a biosimiliar medicine. At present, the primary scientific
assessment is carried out by the authority technical staff,
although in the past, external assessors have been engaged
479Therapeutic Innovation & Regulatory Science (2021) 55:474–489
1 3
Figure1. Regulatory Review Process Map for Zimbabwe Showing Target Times in Calendar Days. The Map Represents the Review and
Authorization of a Product that Goes to Approval After One Review Cycle.
480 Therapeutic Innovation & Regulatory Science (2021) 55:474–489
1 3
under contractual agreement to work within deadlines set
by the agency. Peer-reviewed assessment reports and rec-
ommendations are discussed by the external expert panel
Registration Committee, which makes the final decision on
registration or refusal of a product. The target timeline for
each cycle of scientific assessment is 60 calendar days.
Questions toApplicant (Sponsor)
There is an opportunity for applicants to hold meetings with
the agency staff to discuss questions and queries that arise
during the assessment. A meeting record is generated during
these meetings. Technical advisory meetings are also pro-
vided to local pharmaceutical manufacturers upon request;
unlike other jurisdictions, no fee is charged for these meet-
ings. Questions are collected into a single batch after each
review cycle and only sent to the applicant after the Regis-
tration Committee has made its decision. The applicant is
allowed 60 calendar days to respond after each review cycle;
however, due to manual tracking and requests for extension
to the deadline, company time can exceed this target time.
The scientific review ceases while questions are being pro-
cessed by the sponsor; that is, a clock stop is applied; how-
ever, this time is not excluded when median approval time
is calculated in practice as well as in this study.
Expert Committees
The Registration Committee, which includes representa-
tives from the disciplines of pharmacy, medicine, public
health, toxicology, pharmaceutical science, biotechnology,
and academia, meets once a month and makes decisions on
registration or refusal of a product after the review of the
scientific data by assessors. There is no target time limit for
the Committee procedure. A letter communicating the Com-
mittee’s decision is prepared and questions communicated
to the applicant/sponsor with a 60-day deadline. Responsi-
bility for the decision lies with the Registration Committee,
which uses a consensus process for decision making, and
the MCAZ is mandated to follow its decisions. The criteria
for granting or refusing a marketing authorization/registra-
tion relate only to the assessment of scientific data on qual-
ity, safety, and efficacy and is not dependent on a pricing
agreement or on sample analysis. In some cases, sample
analysis may be done in parallel with the scientific review,
but for the majority of applications, the analysis is carried
out post-registration. Information in the summary of product
characteristics (SmPC) is reviewed, and for generics, this
is expected to be similar to that of the reference/innovator
SmPC. Compliance with local labeling requirements, e.g.,
pharmacological classification, is also a requirement for
registration. Before a product is authorized, the manufac-
turing site must be deemed GMP compliant by the MCAZ
inspectorate and this can be based on an onsite visit or a desk
review where there is a GMP inspection by a recognized
regulatory authority. The sponsor/applicant is informed of
the authority’s intention to approve the registration as well
as any conditions of approval before the authorization is
issued. At that stage, the sponsor is given 30 calendar days
to respond. It can take approximately 60 calendar days from
receiving a positive scientific opinion and the intent to reg-
ister decision to issuing an approval letter and certificate of
registration (Table1).
Approved Products andReview Times
Classification ofApproved Products From 2017–2019, 97%
of approved products were submitted by foreign companies.
The majority of applications approved during the study
period were generics manufactured by foreign companies
followed by NCEs, biologicals/biosimilars, and generics
manufactured by local companies (Fig.2). In 2017, 73% of
the products approved were generics (foreign), 17% were
NCEs, 6% were biologicals/biosimilars, and 4% were gener-
ics (local). In 2018, 86% of products registered were gener-
ics (foreign), 9% were NCEs, 3% were biologicals/biosimi-
lars, and 2% were generics (local). In 2019, 82% of products
registered were generics (foreign), 4% were NCE, 9% were
biologicals/biosimilars, and 5% were generics (local). The
highest number of products approved during the study
period was 195 in 2018 for generics (foreign), 31 in 2017
for NCE, 13 in 2019 for biologicals/biosimilars, and 8 in
2019 for generics (local). There was a decreasing trend in
the number of NCE approved over the study period. All
approved NCEs were sponsored by foreign companies, there
were no locally sponsored NCEs.
Review Times forDifferent Product Types It is significant
that there was an improvement in review times over the
3-year period for all categories of products. The median
overall approval time for all products was reduced from 618
calendar days (n = 183) in 2017 to 518 days (n = 227) in
2018 and 473days (n = 141) in 2019. The median approval
time for generics (foreign) was reduced from 662 calen-
dar days (n = 134) in 2017, to 579 days (n = 195) in 2018
and 554days (n = 116) in 2019. The median approval time
for local generics halved from 611 calendar days (n = 7) in
2017, to 346days (n = 4) in 2018 and 287 days (n = 8) in
2019. The median approval time for NCEs has remained
relatively constant at 299 calendar days (n = 31) in 2017,
306days (n = 21) in 2018, and 239days (n = 6) in 2019. The
median approval time for biologicals/biosimilars was signif-
icantly reduced from 844 calendar days (n = 11) in 2017, to
267days (n = 7) in 2018 and 367days (n = 13) in 2019. The
longest median approval time observed during the study
481Therapeutic Innovation & Regulatory Science (2021) 55:474–489
1 3
period was (844 calendar days) for biologicals/biosimilars
in 2017. The shortest median approval time observed was
239 calendar days for NCEs in 2019(Fig.3).
Comparison of Review Times for Different Models An
improvement in review times was observed across all review
models over the three-year study period. The median approval
time for full review (used for generics and biosimilars not
approved by a reference authority) decreased from 727days
(n = 142) in 2017, to 612days (n = 174) in 2018 and 624days
(n = 105) in 2019. The median approval time for abridged
review (used for NCEs, biologicals, generics, and biosimilars
approved by a reference authority) decreased from 298days
(n = 35) in 2017 to 274 days (n = 36) in 2018 and 272 days
(n = 29) in 2019. The median approval time for verification
review (used for WHO PQ products under the CRP) decreased
from 185days (n = 5) in 2017, to 164days (n = 17) in 2018
and 126 days (n = 7) in 2019. The highest median approval
time was 727days (n = 142) in 2017 for products that had a
full review, and the shortest was 126days (n = 7) in 2019 for
products that had a verification review(Fig.4). In general, the
median approval time for verification review was the shortest
throughout the study period, followed by abridged review then
full review. Products were approved in less than half the time
taken for full review under abridged review and in approxi-
mately a quarter of the time under verification review for all
three years.
Part 4: Good Review Practices: Building Quality
intotheRegulatory Process
General Measures Used toAchieve Quality
GRevPs have been informally implemented by the agency,
using WHO PQ as a standard, including the use of guide-
lines, standard operating procedures, assessment tem-
plates, and screening checklists (Table2). These docu-
ments are not available to the public except the guidelines
and the applicant’s screening checklist, which are available
on the MCAZ website www.mcaz.co.zw. The MCAZ top
management has endorsed and formally adopted an inter-
nal quality policy that gives direction related to the quality
of the review process. The agency produces an assessment
report in English, which undergoes a process of internal
Figure2. Number of Approved Products Classified into Total, Generics (Foreign), Generics (Local), New Chemical Entities, and Biologicals/
Biosimilars.
482 Therapeutic Innovation & Regulatory Science (2021) 55:474–489
1 3
peer review before consideration by the Registration Com-
mittee. A Registration Committee preparatory meeting
serves as a quality assurance check before reports are taken
to the Committee. Applicants/sponsors do not get a full
copy of the assessment report and a redacted assessment
report is not published on the website. Other tools that
build quality into the assessment process are: the avail-
ability of the following platforms for communicating with
Table 2 Status of implementation of good review practices by the MCAZ
483Therapeutic Innovation & Regulatory Science (2021) 55:474–489
1 3
applicants/sponsors and obtaining their feedback;proce-
dures for submitting complaints by applicants/sponsors;
annual stakeholder meetings; individual client meetings;
and liaison meetings with stakeholders such as association
of pharmaceutical manufacturers, retail pharmacists, and
pharmaceutical wholesalers.
Quality Management
The MCAZ has identified quality management to be criti-
cal in achieving its values which are customer focus, con-
tinuous improvement, integrity, and accountability. The
authority strives to be more efficient, to ensure consistency,
and to increase transparency. The following activities are
undertaken to bring about continuous improvement in the
assessment and authorization process: reviewing assessors’
feedback and taking necessary action; reviewing stakehold-
ers’ feedback through, e.g., satisfaction surveys, complaints,
meetings, or workshops and taking necessary action; using
an internal tracking system to monitor quality parameters
such as consistency, timeliness, efficiency, and accuracy; and
carrying out internal quality audits such as self-assessments,
as well as having external quality audits by accredited certi-
fication bodies and using the findings to improve the system.
The authority has a dedicated Quality Unit for assessing
and/or assuring quality in the assessment and registration
process for medicines. Quality management review meet-
ings are held quarterly to monitor implementation of quality
standards across the organization.
Quality intheReview andAssessment Process
Some measures that have been implemented to help improve
the quality of applications and the scientific review are pub-
lication of various guidelines to assist industry as well as
regular feedback to applicants on common deficiencies
observed in applications for registration. These are made
available through the MCAZ website, industry associations,
meetings with stakeholders, and upon request. In addition,
pre-application scientific advice has been given mostly to
local manufacturers/applicants. Quality is monitored through
the minutes of such meetings. The applicant is not given the
contact information of the assessor to discuss their applica-
tion during the review. However, there is some formal con-
tact to discuss the status of pending products. Meetings are
held by appointment on specific days of the week; however,
applicants can send emails at any time requesting status
updates from the administrative regulatory officer. Phone
calls are largely discouraged but may be taken on designated
days.
Shared/Joint Reviews
The MCAZ is a founding member and active participant
of the SADC collaborative medicines registration initia-
tive ZaZiBoNA [3, 7]. The MCAZ acts as a rapporteur,
performing the first review of a product application or as a
co-rapporteur performing the peer review of an application
for products assessed by the initiative for which marketing
authorization in Zimbabwe is sought. The product appli-
cation should have been submitted to a minimum of two
countries to be eligible for review under ZaZiBoNa. The
WHO carries out quality assurance for all reviews under
the initiative. There are formal measures in place to ensure
consistent quality during the review under the initiative
through the use of guidance documents for assessors, use of
common templates for assessment of generic medicines, and
the availability of standard operating procedures. With the
manufacturer’s consent, the agency shares the assessment
report with other regulatory authorities for ZaZiBoNA prod-
ucts. The joint reviews have served as a platform for training,
particularly assessment of the active pharmaceutical ingredi-
ent and biologicals/biosimilars as well as greater exposure
to WHO standards of assessments. To date, ZaZiBoNa has
contributed 11% of total registrations in Zimbabwe in 2017
and 2019, and 4% in 2018 [24].
Training andContinuing Education asanElement ofQuality
A formal training strategy and program for assessors is in
place which includes training at induction, on-the-job train-
ing, internal and external short courses, support for post-
graduate degrees, placements/secondments to more estab-
lished regulatory authorities such as WHO PQ and The
Federal Institute for Drugs and Medical Devices (BfArM) in
Germany, and mentoring of junior assessors by more experi-
enced assessors including peer review. The MCAZ does not
seek direct assistance of more experienced agencies for the
development of SOPs and guidelines; however, guidelines
published by more experienced agencies are referenced,
adapted, or adopted during the development of country
guidelines. The agency collaborates with other agencies in
the training of assessors, e.g., during pre-assessment train-
ing sessions at ZaZiBoNA or as co-facilitators for courses
offered under the MCAZ RCORE. The MCAZ participates
in training offered by WHO and other agencies. Once com-
pleted, a system is in place to evaluate the impact of any
given training on the individual and on the division. The
MCAZ participated in the exercise to determine the level
of competence of assessors using the WHO Global Compe-
tence Framework for Assessors together with other SADC
countries.
484 Therapeutic Innovation & Regulatory Science (2021) 55:474–489
1 3
Transparency oftheReview Process
Being open and transparent in relationships with the
public, professionals, and industry is in line with MCAZ
organizational values and is of high priority. The MCAZ
identified the following top three incentives for assign-
ing resources to activities that enhance the openness of
the regulatory system: political will, the need to increase
confidence in the system, and the provision of assurance
regarding safety measures. Measures to achieve transpar-
ency include the provision of details regarding the regis-
tration process on the MCAZ website including fees pay-
able for the different pathways and regular stakeholder
meetings to interact with applicants and discuss processes
and timelines for approval. In addition, an online register
of approved products is available on the website while
approved, canceled, refused, and withdrawn products
are periodically published in the Government gazette.
Although the MCAZ does not share assessment reports
with applicants, the listed deficiencies or questions raised
during assessment are shared with the applicant, which
they are given a period of 60days to address. When a
product is refused registration, the reasons for the refusal
are shared with the applicant. Furthermore, detailed sta-
tistics are published in the annual reports which the Min-
ister of Health and Child Care presents to the Parliament.
Copies of the MCAZ Annual Reports from 2011–2018
are available on the MCAZ website. Customer satisfaction
surveys and complaint forms, which are freely available on
the website, are used to obtain feedback from applicants
on the quality of the review process.
At present, it is not possible for companies themselves
to track the progress of their applications; however, this is
something that the authority plans to do in the future. How-
ever, companies can follow the progress of their applications
through meetings, e-mail, and telephone contact. Currently,
a database capable of archiving information on applications
in a way that can be searched exists and an electronic track-
ing system has recently been implemented for internal use
only.
Part 5: Quality Decision‑Making Practices
Although some good decision-making practices are imple-
mented, the MCAZ does not have a validated documented
framework in place that forms the basis of the decision to
approve or reject an application. The current process in place
is based on custom and practice. Assessors use a decision
tree to assign relative importance, i.e., critical or not critical
to findings, which ensures decisions/recommendations are
made consistently regardless of the assessor.
One of the challenges identified is that the agency does
not have measures in place to minimize the impact of subjec-
tive influences/biases on the agency’s decision making for
the process to approve or reject an application. In addition,
there is no training provided in the area of quality decision
making in general and neither is there a formal assessment to
periodically measure the quality of decision making within
the agency for the process to approve or reject an appli-
cation. There is, therefore, room for improvement of the
authority’s decision-making process and the implementa-
tion of a framework.
Discussion
The MCAZs vision is to be a leading and effective regula-
tory authority on the African continent. This is evidenced
by its adoption of a robust quality management system
and the implementation of good review practices in line
with international best practice. Historically, the MCAZ
has had the challenge of long registration times. Gwaza
reported a range of 516days to 1673days median time to
registration for the years 2003 to 2015 [15]. To address
this challenge, the MCAZ invested in improving and re-
engineering its processes using international standards
as a benchmark. Management invested financially in the
hiring of a dedicated administrative regulatory officer
to perform validation of applications, thus, preventing
incomplete applications from remaining in the pipeline. In
addition, the hiring of dedicated dossier reviewers and the
introduction of one-week off-site retreats allowed asses-
sors to be dedicated to the review without any interrup-
tion. Management also invested in the development of an
electronic tracking system, which triggered evaluation of
the review process. This resulted in the setting of target
times for all key milestones, adherence to target times, as
well as stricter monitoring of deadlines given to applicants
to respond to questions. The agency decided to limit the
number of review cycles to three, which reduced the time
spent with applicant addressing the same issues. Further-
more, the use of the abridged review model was extended
to generics and biosimilars approved by recognized refer-
ence agencies, where previously it was only used for new
chemical entities and biologicals. The results of this cur-
rent evaluation show that the investment has been worth-
while as the regulatory review process now incorporates
the milestones used by leading regulatory authorities glob-
ally, and therefore, this has led to a decrease in registra-
tion time. The improvement in the process has resulted
in a decrease in the overall median approval time to 473
calendar days (15.8months) in 2019, which is compa-
rable to the review times of 10 to 16months achieved
for new active substances by mature and better resourced
485Therapeutic Innovation & Regulatory Science (2021) 55:474–489
1 3
agencies [25]. The MCAZ has also shown initiative in
using risk stratification approaches such as the abridged
review pathway and participation in the WHO CRP. This
has allowed the authority to focus its limited resources on
the full review of applications for products that are not
approved elsewhere.
Performance Against Set Targets
The results of this study show that the authority is cur-
rently meeting the targets set for overall approval time
(480days) and abridged review (270days). Although
the time taken for approval using the verification review
(WHO CRP) is above the target (90days), it is still very
short (125days in 2019). The time taken for full review
is much higher than the target of 480days (624days
in 2019). Some of the reasons that contribute to a long
approval time are a long queue time (the time a prod-
uct spends in the queue from receipt to the start of the
scientific assessment), an inadequate number of experi-
enced reviewers, and numerous requests from applicants
for deadline extensions to respond to reviewer questions.
The queue time is indicative of the resources available
to perform the work and a target of 180days is too long,
reflecting the need for an evaluation of the adequacy of
human resources available to review products as well as
the ability of the MCAZ to retain staff with key competen-
cies and expertise. Gwaza reported that the authority had
a relatively young workforce of assessors/reviewers, two
of whom had doctorates at that time in 2014 [15]; how-
ever, when compared with results from the current study
conducted five years later, the workforce is still relatively
young and the two reviewers with doctorates are no longer
a part of the team of reviewers. This points to a problem of
high staff turnover and poor skills retention, which needs
to be addressed if the queue time and overall timelines are
to be improved.
New Chemical Entities
While generics play an important and critical role in ensur-
ing access to life-saving treatment in LMICs, the need for
new and innovative medicines cannot be overlooked. Some
patients have reported better outcomes with innovator brands
compared with generic products [26], and NCEs should be
approved and readily available on any market. This will
reduce the cost of the medicine, unlike the situation in which
the unregistered NCE is imported for the patient under sec-
tion75, a provision in the Medicines and Allied Substances
Control Act, which waives the requirement for registration
of unregistered medicines imported on a doctor’s prescrip-
tion and named patient basis. NCEs or innovative products
are normally only launched onto the African market after
a number of years of approval and use in well-resourced
markets [7] making them low-risk products with established
efficacy and safety, which have undergone a rigorous review
by a mature agency. The results of this study show that the
MCAZ uses risk stratification for all NCEs by conducting
an abridged review. This process has proven effective, as
the median approval time for NCEs was the lowest of all the
product types registered in Zimbabwe, ranging from 239
to 306 calendar days (8–10months) over the study period,
and this has not resulted in any increase in the incidence
reports of post-marketing adverse events. The review times
for NCEs are comparable to the time taken by mature agen-
cies and much lower than the 3–6years reported for review
of new active substances in other countries in the region who
conduct a full review [19, 20]. The results of this study show
that all products are placed in the same queue for review
regardless of the type of review to be conducted. This is dif-
ferent from some countries in the region where applications
for NASs are placed in a different queue from applications
for generic medicines [19]. There has been a decrease in the
number of NCEs registered in Zimbabwe from 2017 to 2019
which could be due to various reasons, such as economic
factors beyond the regulator’s control. However, the MCAZ
can encourage submission or registration of NCEs by having
a separate queue for these products since the numbers are
very low compared with generics, and the type of review
conducted is different. It is also likely that the NCEs will
be addressing an unmet medical need. This will be a pro-
cess improvement that will further reduce approval time and
improve access to new and innovative life-saving medicines
by patients in Zimbabwe.
Biologicals andBiosimilars
The LMICs in the African region suffer the highest bur-
den of infectious diseases such as HIV/AIDS and tubercu-
losis [27, 28], which has resulted in most of the countries
developing policies to promote the prescription and use of
generic medicines [29] to ensure access to treatment by as
many patients as possible at affordable prices. In addition,
in recent years, there has been a rise in the prevalence of
non-communicable diseases such as cancer in LMICs [30,
31] and the cost of biologicals used for treatment of diseases
such as cancer is prohibitive, leading to a rise in the use of
biosimilar medicines. Review of applications for registration
of biologicals and biosimilars requires different competen-
cies to those required for small molecules. There is also a
component of benefit-risk assessment to be considered for
biosimilars that is not critical for small-molecule generic
medicines.
From this study, we found that most biosimilars received
in Zimbabwe require a full review as they are not approved
486 Therapeutic Innovation & Regulatory Science (2021) 55:474–489
1 3
by any of the reference authorities. The median approval
time for biosimilars and biologicals of 844 calendar days
(28months) in 2017 was the highest for all product types
during the study period. This was because in 2017, the
agency had only just established a dedicated unit for bio-
logical products with three reviewers, and there was limited
knowledge and experience to review these products. How-
ever, the greatest reduction in median approval time over the
study period was observed for biologicals and biosimilars
from 844 calendar days in 2017 to 267days in 2018 owing
to the reviewers gaining more knowledge and expertise in
the area as well as the use of abridged review for biologicals
and biosimilars approved by a recognized reference author-
ity. A study should be conducted to determine why more
manufacturers/applicants of biosimilars approved by refer-
ence authorities are not seeking market authorization for
their products in the LMICs. Such products would drasti-
cally reduce the cost of treatment for patients who often have
to pay out of pocket for treatment and therefore justifies a
shorter registration times for such products.
Local Products
Markets eroded by sub-standard and falsified medicines due
to weak regulation, inadequate technology, outdated equip-
ment and facilities, inadequate research and development,
and lack of appropriately skilled personnel were cited as
some of the challenges faced by the pharmaceutical manu-
facturers in Africa in the Pharmaceutical Manufacturing
Plan for Africa (PMPA) business plan developed by a part-
nership of the African Union Commission (AUC) and the
United Nations Industrial Development Organization [32].
The figures presented in this study on the number of generics
registered from local and foreign companies, show that local
manufacturers contributed 5%, 2%, and 6.5% respectively
of the generic products registered from 2017–2019. Recog-
nizing the role that local manufacturers can play in reduc-
ing the cost of medicines and contributing to public health,
the MCAZ has recently adopted a policy to prioritize the
review of locally manufactured medicines. This has resulted
in a reduction in the median approval time (inclusive of the
applicants’ time) of local generics from 611 calendar days
(20months) in 2017 to 346days (11.5months) in 2018,
and 287 calendar days (9.5months) in 2019. The MCAZ
also plays a capacity-building role through the collabora-
tion on the GMP roadmap for manufacturers and trainings
offered to industry through its RCORE. It is envisaged that
as the challenges identified in the PMPA business plan are
addressed, the product portfolio of local manufacturers
as well as their presence on the market will increase. The
median approval time can be further reduced by limiting the
number of review cycles and adhering to the deadlines for
applicants to respond to questions (Figs.3, 4).
Electronic Tracking System
The MCAZ has recently implemented an electronic tracking
system that should enable easier tracking and reporting of
Figure3. Median Approval Times (Inclusive of Applicants’ Time) for All Products (Overall), Generics (Foreign), Generics (Local), New Chem-
ical Entities, and Biologicals/Biosimilars.
487Therapeutic Innovation & Regulatory Science (2021) 55:474–489
1 3
the clock stop, clock start. This will help both applicants/
sponsors and the agency to see their contribution to the over-
all approval time. At present, the authority’s target timelines
are set and measured inclusive of the applicant’s time. The
shortcoming of this approach is that the authority includes
company time when measuring its performance, yet this is
not within its control. An element of good review practices
yet to be implemented by the MCAZ is to enable applicants
to track the progress of their applications. The authority
should consider further improving the electronic tracking
system to allow applicants to submit applications online and
track their progress.
The MCAZ successfully implements the three types of
review models in line with the international standards. The
milestones in the review process are formally recorded,
and targets have been set for each milestone. Performance
against set targets is monitored. All except four indicators
for good review practices are either formally or informally
implemented. Although good decision-making practices are
implemented, there is need to have a formal decision-making
framework in place.
Recommendations
The following opportunities for system/process improve-
ment were identified from the study:
The adequacy of human resources available to review
products as well as the ability of the authority to retain
staff with key competencies and expertise should be
evaluated.
The authority should consider mainly the agency time
when setting target timelines and measuring performance
and the timeframe for the applicant’s response should
only be extended if there is a good rationale as this affects
overall approval time.
Applications should be placed in different queues accord-
ing to review type, e.g., products requiring full review
should have a separate queue from products eligible for
abridged or verification review.
The MCAZ should, where possible, pursue formal agree-
ments with chosen reference agencies to facilitate the
sharing of unredacted assessments reports or alternatively
encourage manufacturers to use the recently published
WHO collaborative procedure to facilitate the accelerated
Figure4. Median Approval Times (Inclusive of Applicants’ Time) for Different Review Models; i.e., Overall, Full Review, Abridged Review,
and Verification Review (World Health Organization WHO Collaborative Medicines Registration Procedure).
488 Therapeutic Innovation & Regulatory Science (2021) 55:474–489
1 3
registration of products approved by mature regulatory
agencies [33].
The authority should consider improving the recently
implemented electronic tracking system to allow applicants
to track the progress of their applications in line with good
review practices.
Since there is no formal decision-making framework in
place, the agency should implement a structured approach
to decision making using a validated tool such as “Qual-
ity of Decision-Making Orientation Scheme (QDOS)”
which identifies the 10 quality decision-making practices
(QDMPs)
The current templates and the benefit-risk framework used
for abridged reviews should be evaluated and compared
with those of comparable or reference agencies to deter-
mine if there is need for improvement.
Conclusions
This study has evaluated the current MCAZ regulatory
review process. Key milestones and timelines have been
identified, and the measures used for GRevP have been
considered. The MCAZ performs a full review assessment
of applications for registration of generics and biosimilars
not approved by a reference authority and uses reliance to
conduct an abridged review for NCEs, biologicals, biosim-
ilars, and generics approved by recognized reference regu-
latory authorities and verification review for WHO-pre-
qualified products. A Quality Management System (ISO
9001) and quality policy are implemented. Overall, the
results of this study demonstrated that the target timelines
set and communicated by the authority to stakeholders are
realistic and what is achievable with the current resources
available. This transparency is commendable and enables
applicants/sponsors to plan appropriately. The findings
from this study present opportunities for an enhanced
regulatory review and improvement of the current pro-
cess. The study will enable the authority to easily identify
the areas requiring additional resources and improvement.
This study will also make it possible for comparison of
Zimbabwe, a lower middle-income country, with similar
countries in the SADC region, the African continent, and
similar sized higher income countries beyond Africa with
the goal to improve the regulatory review process in Zim-
babwe and patients’ access to life-saving medicines. The
approach taken here in this evaluation could also provide
a model for other low- to middle-income countries in the
African region.
Acknowledgments
This research was supported by an unrestricted grant from the Bill and
Melinda Gates Foundation.
Compliance with Ethical Standards
Conflict of interest
The authors report no conflicts of interest in this work.
Open Access
This article is licensed under a Creative Commons
Attribution 4.0 International License, which permits use,
sharing, adaptation, distribution and reproduction in any
medium or format, as long as you give appropriate credit
to the original author(s) and the source, provide a link to
the Creative Commons licence, and indicate if changes were
made. The images or other third party material in this article
are included in the article’s Creative Commons licence,
unless indicated otherwise in a credit line to the material. If
material is not included in the article’s Creative Commons
licence and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to
obtain permission directly from the copyright holder. To
view a copy of this licence, visit http://creat iveco mmons
.org/licen ses/by/4.0/.
References
1. World Bank. Country data: Zimbabwe 2018. https ://data.world
bank.org/?locat ions=ZW. Accessed June 16, 2020.
2. International Monetary Fund. Zimbabwe 2017. https ://www.imf.
org/en/Count ries/ZWE Accessed June 16, 2020.
3. Medicines Control Authority of Zimbabwe. http://www.mcaz.
co.zw/index .php/downl oads/categ ory/7-regul ation s Accessed 3
April 2020.
4. World Health Organization. Zimbabwe Medicines Quality Lab
gets WHO approval. https ://www.who.int/medic ines/news/zwe_
med_quali ty_lab/en/. Accessed 4 April 2020.
5. Standards Association of Zimbabwe ISO 9001 certified companies
for management systems. Pg 17 number Q320. http://saz.org.zw/
regis tered -entit ies/. Accessed October 2, 2020.
6. Medicines Control Authority of Zimbabwe (MCAZ). ZAZIBONA
Collaborative Medicines Registration Process. Available from:
https ://www.mcaz.co.zw/inde x .php/alter nativ e-submi ssion -pathw
ays. Accessed 2 October 2020.
7. Sithole T, Mahlangu G, Salek S, Walker S. Evaluating the success
of ZaZiBoNa, the Southern African Development Community
Collaborative Medicines Registration Initiative. Ther Innov Reg
Sci. 2020. https ://doi.org/10.1007/s4344 1-020-00154 -y.
8. Rägo L, Santoso B. Drug regulation: history, present and future.
In: van Boxtel CJ, Santoso B, Edwards IR, editors. Drug ben-
efits and risks: International textbook of clinical pharmacology.
Revised 2nd ed., 65–77. Amsterdam: IOS Press and Uppsala
Monitoring Centre; 2008.
489Therapeutic Innovation & Regulatory Science (2021) 55:474–489
1 3
9. World Health Organization. World Health Organization concept
note: A framework for evaluating and publicly designating regu-
latory authorities as WHO-Listed authorities. WHO Drug Info.
2019;33(2):139–58.
10. World Health Organization. Essential medicines and health prod-
ucts. WHO Global Benchmarking Tool (GBT) for evaluation of
national regulatory systems. https ://www.who.int/medic ines/regul
ation /bench marki ng_tool/en/. Accessed 29 May 2020.
11. World Health Organization. Regulatory system strengthening
for medical products. 2014 24 May. Contract No: World Health
Assembly 67.20. https ://apps.who.int/gb/ebwha /pdf_files /WHA67
-REC1/A67_2014_REC1-en.pdf. Accessed 13 June 2020.
12. Sillo H. WHO benchmarking of regulatory systems. Updates on
benchmarking and IDP implementation. World Health Organisa-
tion Covid-19 Regulatory Round-Up meeting (virtual), May 2020.
13. World Health Organization Africa. Tanzania Food and Drug
Authority becomes the first to reach level 3 of the WHO bench-
marking programme. https ://www.afro.who.int/news/tanza nia-
food-and-drug-autho rity-becom es-first -reach -level -3-who-bench
marki ng-progr amme. Accessed 16 June 2020.
14. Ghana Foods and Drugs Authority (FDA) attains maturity level
3 regulatory status. Available from: https ://www.afro.who.int/
news/ghana -foods -and-drugs -autho rity-fda-attai ns-matur ity-level
-3-regul atory -statu s.
15. Gwaza L. Thesis: Adjusted indirect treatment comparisons of bio-
equivalence studies: Utrecht University, The Netherlands; 2016.
https ://dspac e.libra ry.uu.nl/handl e/1874/33747 4.
16. Alsager S, Hashan H, Walker S. The Saudi Food and Drug
Authority: shaping the regulatory environment in the Gulf Region.
Pharm Med. 2015;29(2):93–103.
17. Al Haqaish WS, Obeidat H, Patel P, Walker S. The Jordan Food
and Drug Administration: comparison of its registration process
with Australia, Canada, Saudi Arabia and Singapore. Pharm Med.
2017;31(1):21–30.
18. Ceyhan EM, Gürsöz H, Alkan A, Coşkun H, Koyuncu O, Walker
S. The Turkish Medicines and Medical Devices Agency: com-
parison of its registration process with Australia, Canada, Saudi
Arabia, and Singapore. Front Pharmacol. 2018;9:9.
19. Keyter A, Gouws J, Salek S, Walker S. The regulatory review
process in South Africa: challenges and opportunities for a new
improved system. Ther Innov Reg Sci. 2018;52(4):449–58.
20. Keyter A, Salek S, Gouws J, Banoo S, Walker S. Evaluation of the
performance of the South Africa Regulatory Agency: recommen-
dations for improved patients’ access to medicines. Ther Innov
Reg Sci. 2020;54(4):878–87.
21. McAuslane N, Cone M, Collins J, Walker S. Emerging markets
and emerging agencies: a comparative study of how key regula-
tory agencies in Asia, Latin America, the Middle East, and Africa
are developing regulatory processes and review models for new
medicinal products. Drug Info J. 2009;43(3):349–59.
22. Measuring process and performance in regulatory agencies: The
OpERA Programme. https ://www.cirsc i.org/wp-conte nt/uploa
ds/2020/02/CIRS-RD-Brief ing-74-OpERA -progr amme.pdf.
Accessed 2 Oct 2020.
23. World Health Organization. Collaborative procedure for acceler-
ated registration. https ://extra net.who.int/prequ al/conte nt/colla
borat ive-proce dure-accel erate d-regis trati on. Accessed 2 Sept
2019.
24. Sithole T. Collaboration, convergence & work sharing in the Afri-
can context, ZAZIBONA. DIA North Africa Regulatory Con-
ference; Cairo, Egypt, 2019. https ://dia.covr.be/cmPor tal/Searc
hable Dia/19114 /confi g/searc hable #!sessi ondet ails/00000 94290
_0. Accessed 13 Nov 2019.
25. Bujar M, Liberti L. R&D Briefing 65: New drug approvals in six
major authorities 2007–2016: focus on the internationalisation of
medicines. London: Centre for Innovation in Regulatory Science;
2017.
26. Dunne S, Shannon B, Dunne C, Cullen W. A review of the differ-
ences and similarities between generic drugs and their originator
counterparts, including economic benefits associated with usage
of generic medicines, using Ireland as a case study. BMC Phar-
macol Toxicol. 2013;14:1.
27. Corbett EL, Watt CJ, Walker N, Maher D, Williams BG, Rav-
iglione MC, etal. The growing burden of tuberculosis: global
trends and interactions with the HIV epidemic. Arch Intern Med.
2003;163(9):1009–21.
28. World Health Organization. 2019 Global Tuberculosis Report,
Annex 2 Country profiles for 30 High TB burden countries. https
://www.who.int/tb/publi catio ns/globa l_repor t/tb19_Repor t_count
ry_profi les_15Oct ober2 019.pdf?ua=1. Accessed 17 Mar 2020.
29. Kaplan WA, Ritz LS, Vitello M, Wirtz VJ. Policies to promote
use of generic medicines in low- and middle-income countries:
a review of published literature, 2000–2010. Health Policy.
2012;106(3):211–24.
30. Bos ER, Jamison DT, Bainga F, etal, editors. Disease and mor-
tality in sub-Saharan Africa, 2nd ed. Washington, DC: The Inter-
national Bank for Reconstruction and Development/The World
Bank. 2006.
31. Miranda JJ, Kinra S, Casas JP, Davey Smith G, Ebrahim S. Non-
communicable diseases in low-and middle-income countries:
context, determinants and health policy. Trop Med Int Health.
2008;13(10):1225–34.
32. The African Union Development Agency New Partnership for
Africa Development (AUDA NEPAD). Pharmaceutical Manu-
facturing Plan for Africa Business Plan. https ://www.nepad .org/
publi catio n/pharm aceut ical-manuf actur ing-plan-afric a Accessed
23 June 2020.
33. World Health Organization. WHO technical report series 1010,
Annex 11, 2018, Collaborative procedure in the assessment and
accelerated national registration of pharmaceutical products and
vaccines approved by stringent regulatory authorities. https ://
extra net.who.int/prequ al/sites /defau lt/files /docum ents/TRS_1010-
2018_Annex 11.pdf. Accessed 4 April 2020
... 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. ...
Article
Full-text available
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 could be due to 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,(15)(16)(17) for the national procedure, which negatively impacts the worksharing initiative. The use of a regional unit to coordinate assessments would also assist in addressing the identified challenges, particularly in a resource-constrained setting. ...
Article
Full-text available
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.
... As a result, one of the challenges that has been identified with this initiative is the fact that differences in country review processes result in questions to applicants for the same product being sent at different times by the countries, affecting registration timelines and negating the benefit of simultaneous access to various markets. Sithole et al. therefore recommended that the regulatory review processes in the individual participating countries be reviewed and the outcomes compared (3,5). The aim of this study therefore was to review and compare the registration processes of regulatory authorities of Mozambique, Namibia, South Africa, Tanzania, Zambia, and Zimbabwe to develop recommendations for better alignment, while presenting an opportunity for the countries to learn from each other and enhance their regulatory review and patients' access to life-saving medicines. ...
Article
Full-text available
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.
... Reliance involves either a verification or an abridged review 17,18 and takes into account, either partly or fully, the assessment done by other agencies. The collaborative procedures for WHO-prequalified products or products approved by stringent regulatory authorities are examples of established reliance or recognition mechanisms as applicable to individual participating authorities. ...
Article
Full-text available
There is a critical skills gap on the African continent in regulatory sciences, and an acknowledged need to develop a long‐term strategy for training and professional development of African regulatory personnel. Capacity building programs for African regulators should link education, training and research with career development in an approach that combines an academic base and experiential learning aligned within a competency framework. A regulatory ecosystem that engages with a broad range of stakeholders will mean that expertise in the ever‐expanding field of regulatory science filters into teaching and research in a symbiotic way. In this way capacity development interventions will be a collaborative approach between the learning context (academic and training institutions) and the performance context (regulatory agencies and industry), which will ultimately best serve the patients. Monitoring and evaluation of capacity development interventions will be essential to show value of investments and ultimately guide continued funding and sustainability. This paper reviews the skills and human capacity gaps, reports on regulatory assessment pathways used in Ghana, South Africa and Zimbabwe and outlines a staged tactical approach for Africa that builds on previous efforts to strengthen African regulatory ecosystems.
Background: Benchmarking regulatory systems of low- and middle-income countries with mature systems of comparable size provides an opportunity to identify gaps, enhance review quality, and reduce registration timelines, thereby improving patients' access to medicines. The aim of this study was to compare the medicines registration process of the Medicines Control Authority of Zimbabwe (MCAZ) with the regulatory processes in Australia, Canada, Singapore, and Switzerland. Methods: A questionnaire that standardizes the review process, allowing key milestones, activities and practices of the five regulatory authorities was completed by a senior member of the divisions responsible for issuing marketing authorizations. Results: The MCAZ has far fewer resources than the regulatory authorities in the comparator countries, but employs three review models, which is in line with international best practice. The MCAZ registration process is similar to the comparator countries in key milestones identified and monitored, but differs in the target timelines for these milestones. The MCAZ is comparable to the comparator authorities in implementing the majority of good review practices, although it significantly lags behind in transparency and communication. Conclusion: This study identified the MCAZ strengths and opportunities for improvement, which if implemented, will enable the achievement of its vision to be a leading regulatory authority in Africa.
Article
Full-text available
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.
Article
Full-text available
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.
Article
Full-text available
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.
Article
Full-text available
Introduction: Regulatory agency comparisons can be of more value and facilitate improvements if conducted among countries with common challenges and similar health agency characteristics. A study was conducted to compare the registration review model used by the Turkish Medicines and Medical Devices Agency (Türkiye Ilaç ve Tibbi Cihaz Kurumu; TITCK) with those of four similar-sized regulatory agencies to identify areas of strength and those requiring further improvement within the TITCK in relation to the review process as well as to assess the level of adherence to good review practices (GRevP) in order to facilitate the TITCK progress toward agency goals. Methods: A questionnaire was completed and validated by the TITCK to collect data related to agency organizational structure, regulatory review process and decision-making practices. Similar questionnaires were completed and validated by Australia's Therapeutic Goods Administration (TGA), Health Canada, Singapore's Health Science Authority (HSA), and the Saudi Arabia Food and Drug Administration (SFDA). Results: The TITCK performs a full review for all new active substance (NAS) applications. Submission of a Certificate of Pharmaceutical product (CPP) with an application is not required; however, evidence of approval in another country is required for final authorization by the TITCK. Pricing data are not required by the TITCK at the time of submission; however, pricing must be completed to enable products to be commercially available. Mean approval times at the TITCK exceeded the agency's overall target time suggesting room for improved performance, consistency, and process predictability. Measures of GRevP are in place, but the implementation by the TITCK is not currently formalized. Discussion: Comparisons made through this study enabled recommendations to the TITCK that include streamlining the good manufacturing practice (GMP) process by sharing GMP inspection outcomes and certificates issued by other authorities, thus avoiding the delays by the current process; removing the requirement for prior approval or CPP; introducing shared or joint reviews with other similar regulatory authorities; formally implementing and monitoring GRevP; defining target timing for each review milestone; redefining the pricing process; and improving transparency by developing publicly available summaries for the basis of approval.
Article
Full-text available
Generic medicines are those where patent protection has expired, and which may be produced by manufacturers other than the innovator company. Use of generic medicines has been increasing in recent years, primarily as a cost saving measure in healthcare provision. Generic medicines are typically 20 to 90% cheaper than originator equivalents. Our objective is to provide a high-level description of what generic medicines are and how they differ, at a regulatory and legislative level, from originator medicines. We describe the current and historical regulation of medicines in the world's two main pharmaceutical markets, in addition to the similarities, as well as the differences, between generics and their originator equivalents including the reasons for the cost differences seen between originator and generic medicines. Ireland is currently poised to introduce generic substitution and reference pricing. This article refers to this situation as an exemplar of a national system on the cusp of significant health policy change, and specifically details Ireland's history with usage of generic medicines and how the proposed changes could affect healthcare provision.
Article
Objective This study outlines the current regulatory review process and good review practices (GRevPs) at the Jordan Food and Drug Administration (JFDA) and compares them with those of regulatory agencies in Australia, Canada, Saudi Arabia and Singapore to gauge how well the JFDA is performing. We identify opportunities for further development of the JFDA as a key global reference agency. Methods Personnel within the JFDA completed a questionnaire comprising four sections: organisation, key milestones, review timelines, and GRevPs. The same questionnaire was used concurrently to gather information from Australia’s Therapeutic Goods Administration (TGA), Health Canada, the Saudi Food and Drug Authority (SFDA) and Singapore’s Health Sciences Authority (HSA). ResultsThe JFDA conducts an abridged review for new active substances and requires a certificate of pharmaceutical product (CPP) at the time of submission and 6 months of pharmacovigilance data at the time of the final review as well as full pharmaceutical, chemistry, manufacturing and controls (CMC) and clinical data at the time of submission. A written summary and tabulated data are required for non-clinical data. The four comparator agencies conduct full assessments; the SFDA also requires a CPP, and the JFDA and SFDA both require pricing information at submission. All agencies have established target timelines, and the JFDA, SFDA, TGA and HSA currently exceed those targets. All agencies have also developed GRevPs as well as training and continuous-improvement processes. Conclusions The JFDA has achieved significant success in its role as a regulatory agency by setting and implementing clear regulations in line with international guidance. It is recognised as a training centre in the region, with considerable achievements in the development of its activities by simplifying and improving requirements, procedures and actions. It also publishes information regarding guidance, procedures, drug application submissions and registration dates for all new chemical entities on its website. The relationship between the JFDA and the pharmaceutical sector in Jordan has resulted in balanced, practical, internationally compatible regulations and demonstrates a viable model of collaboration. To assist the JFDA in its efforts to become a key global reference agency, it is suggested that the agency explore a risk-stratification approach to the regulatory review; accept CPPs after dossier submission or use alternatives to the CPP; conduct pricing evaluations in parallel with scientific assessments; establish defined target times for review milestones and improve internal tracking systems to monitor these milestones; and make certain information transparent to all stakeholders by publishing a summary basis of approval.
Article
Objective This study sought to assess the current regulatory review process in Saudi Arabia, identify the key milestones, evaluate the measures used for Good Review Practices (GRevP) and to suggest opportunities for an enhanced regulatory review of medicines. Methods A questionnaire completed by the Saudi Food and Drug Authority (SFDA) was divided into three parts: Organisation of the Agency, Key Milestones and Timelines and GRevP. Results Currently the SFDA carries out a full assessment for the review of all major applications, although they currently lack the expertise to evaluate the preclinical portion of the product file. A Certificate of Pharmaceutical Product (CPP) is required at the time of registration and a pricing agreement internally must be developed before authorisation. Applications may have to wait 2-6 months before review, although priority products are taken out of the queuing system. The median review times for new active substances from submission to approval were 340 working days (2011) and 372 working days (2013); however, the target time was 290 working days. Standard operating procedures (SOPs), review templates and an electronic submission tracking system are in place, but the GRevP framework is still evolving. Conclusion Based on the available resources and capabilities, the SFDA is unable currently to meet its overall target timelines, partly due to the sponsor’s time in responding to agency questions. Therefore, it either needs to increase its resources or to implement a risk stratification system based on the Singapore model, which takes into account reviews by reference agencies. The SFDA is encouraged to develop GRevP guidelines to ensure the quality of the review.
Article
An ongoing study has been set up by the CMR International Institute for Regulatory Science to record and analyze the regulatory procedures for the authorization of new medicines in 13 key countries, outside the ICH regions, where the pharmaceutical market is expanding or the regulatory agency plays an important role in regional development. These countries are Argentina, Brazil, Mexico, Egypt, Saudi Arabia, South Africa, China, India, Indonesia, Malaysia, Singapore, South Korea, and Chinese Taipei. In the study, data were collected from senior personnel in the national agencies and from multinational pharmaceutical companies on the review and assessment processes for new active substances (NASs) and major line extensions (MLEs). The quality measures being applied by the agencies to monitor those procedures were also recorded. The design of the study collected information for a status report at one time point, as summarized here, but also provides the basis for recording and benchmarking the progress and changes made by the agencies over time. A cross-comparison of information from the authorities indicated that regulatory aspirations, barriers, and priorities are essentially similar across agencies. The review steps are also similar although there are major differences in the assessment process. Most agencies are using risk stratification methods for their review of new medicines, based on the level of regulatory scrutiny the product has already undergone by agencies elsewhere. There is an awareness of the importance of building quality into agencies' regulatory processes and practices and this is a changing and evolving area.
Article
Review the literature on the impact of policies designed to enhance uptake of generic medicines in low and middle income countries (LMICs). We searched for publications related to generic medicines policies (January 2000-March 2010) and did a bibliometric, descriptive analysis of the dataset in addition to an analysis of studies evaluating the impact of pro-generic policies. We repeated a subset of this larger search in January 2012. Of the 4994 articles screened, 315 (6.3%) full-text publications were related to generic medicines policies. Of these 315, 236 (75%) dealt with generic medicine policies in high-income countries, and 79 (25%) with policies in LMICs. In total, we found only 10 evaluation studies looking at the impact of competition, trade, pricing and prescribing policies on generic medicine price and/or volume. Key barriers to implementing generic medicine policies in LMICs are negative perceptions of stakeholders (e.g., generics are of lower quality) plus perverse private sector financial incentives to sell products with the highest profit margin. Other relevant barriers are legal/regulatory, such as the absence of generic substitution regulations. There also exists a general difficulty in promoting generics due to a lack of transparency in the pharmaceutical supply and distribution system, for example, a lack of price information provided by health care provider organizations to physicians. There is little policy evaluation to determine which pro-generic policies increase generic medicines utilization in LMICs. Ensuring a functioning medicines regulation authority, creating a reasonably robust market of generic medicines and aligning incentives for physicians, consumers and drug sellers are necessary prerequisites for increasing the uptake and use of generic medicines.