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Ethiopian Food, Medicine and
Healthcare Administration
and Control Authority
EFMHACA

Quality health services and products to all Citizen EFMHACA
Overview of Regulation: Review and
Authorization of Pharmaceutical Products in
Ethiopia
Heran Gerba, B.Pharm, MSc.
Deputy Director General,
Ethiopian Food, Medicine and Healthcare
Administration and control Authority (EFMHACA)
September 12, 2018
Seoul, Korea

Outline of the Presentation
 Introduction
 Pillars of the health sector
 Mission,Vision
 Main Functions of the regulatory Authority
 Market authorization process
 Reply to Questionnaires

•Ethiopia is considered as a
gate way to Africa as it is a
seat for AU, ECA & many
international organizations;
the political capital for Africa
•Ethiopia is politically and
macro-economically stable
•Fast pro-poor growth
(average 11% GDP growth for
the last 10 years)
•Good governance &
attractive investment law
ETHIOPIA AT A GLANCE…

About Ethiopia
Population
 One of the fastest growing
economies in the world
 –11% average growth over the
past 13 years
Economics
 One of the top destinations for
foreign direct investment (FDI)
 Ethiopia accounts for 18.5% of all
jobs created through FDI in
Africa
Health
 Second most populous country
in Africa
 –>100 million people, growing at
2.3 million annually
 •Young and productive age
group accounts for 60% of the
population
Rapid
economic
growth
Favorable
destination
for FDI
Young and
productive
population
Clear vision
for
development
Literacy
Total: 100m (est.
2017)
GDP/capita: $739
(2015/16)
FDI inflow: $3.2bn
(2016)
FDI growth: 46% (2016)
Health spend: $2.7bn
Health spend/capita: $27
Health spend/GDP: 5%
Availability of EDMs*:
~70%
49% of total
population
Vision 2025: become leading
manufacturing hub in Africa.
•Foreign investment is key focus of
the government .
•Wide-ranging incentives in
priority sectors

About Ethiopia
Ethiopia is building mega infrastructure projects to
boost investment, which will capitalize on its existing
geographic and market access advantages
Electricity rate: 3
cents/kwh
•Massive investment
in renewable energy
generation
•Dedicated power
sub-station in all
industrial parks
New electric
railway
connecting
industrial parks
to Djibouti port
–4-12 hour travel
time
Africa’s aviation
hub: over 100
international
passenger, & 36
cargo destinations
•Ethiopian
Airlines:World-
class airline
Industrial parks located
in economic corridors
•13 parks in total: 2
operational,11
upcoming
•Specialized in priority
sectors (including one
upcoming
pharmaceuticals park)
•Generous incentives

About Ethiopia
The Government of Ethiopia considers pharmaceutical
manufacturing a priority for its economic growth
strategy.
Pharmaceutical manufacturing identified as
priority sector in the second Growth and
Transformation Plan (GTP II)
–Dual benefit of increasing access to medicines and
promoting rapid industrialization of the country
•Ethiopia is one of the first African countries to
develop national strategy for pharmaceutical
manufacturing
–Strategy: to grow exports in addition to substituting
imports and improving access to medicines
•The Government will develop state of the art
Industrial Parks specialized in pharmaceutical
manufacturing Goal:To become a
pharmaceutical manufacturing hub in Africa

Pillars of the health sector
 According to the National health Policy,
the Health sector is organized into
three pillars
1. Service provider
2. Service purchaser
3. Health regulator

Ethiopian health system organization/
tier system
Currently we have more than 20,000 health facilities

Pillars of the health sector con’t
REGULATOR

Mission,Vision and objectives
Mission
 To promote and protect the public health by ensuring safety
and quality of products and health service through
registration, licensing and inspection of health professionals,
pharmaceuticals & food establishments, and health facilities
and provision of up-to-date regulatory information while
promoting rational medicines use
Vision
 Quality health services and products to all Citizens

19 Port of Entry
and Exit
REGIONAL
REGULATORY
BODIES [Region,
Zone andWoreda
level]
The Regulatory sector: system
structure
Northern Ethiopia
Eastern Ethiopia
North Western Southern Ethiopia
South Western North Eastern

Regulatory tools: Hierarchy of law
in Ethiopia
Constitution
Proclamations
Regulations
Directives
Guidelines

“To transform the Ethiopian pharmaceutical manufacturing sector into a fully
GMP-compliant, competitive and innovative industry that meets the national
needs of essential medicines and serves the African market by 2025”
National Strategy & Plan of Action for Pharmaceutical
Manufacturing Development in Ethiopia
(2015-25)
Vision:
14

Pharmaceutical Supply Chain
 Pharmaceutical Fund and Supply Agency
 Agency Reporting to FMoH
 Distributes more than US $ 850 million
dollars worth of health commodities
annually, supplying nearly 20,000 health
service delivery points: hospitals, health
centers and health posts.

Value chain Level I: Import Finished
Pharmaceutical Products
 Any medicine should be granted MA before entering into the
market of Ethiopia [Proclamation No 661/2009 &
Regulation no. 299/2013].
 New for Ethiopian market….Safety and Efficacy data
needs to be reviewed by NDAC:
 Marketing authorization process requires….three process:
Site inspection of facility/GMP Waiver … in compliance of
Good Manufacturing practice (cGMP) Inspection
Dossier Assessment … in compliance of safety, efficacy &
Quality to grant…..Market Authorization
Quality Control testing … shifted from Premarket
testing…… Consignment testing.

 With the Current Procedure:- Ethiopia’s registered
Human Medicine List is only 3800 in number.
 The Pharmaceuticals Procurement List contains
around 1373 types including medicines, reagents,
medical equipments etc.
 We need to increase our registered medicine list as
number of health facilities increases and health
insurance starts.

 Market authorization process based on authority’s
Expediting Medicine Market Authorization
Strategies (2017).
 Objective: to transform regulatory review processes &
dramatically boost access to safe, quality and
efficacious medicines through expedited Market
Authorization process.
 Strategic direction for dossier assessment
 Strategic direction for GMP inspection
 Strategic direction for Quality testing

Strategic Direction for Dossier Assessment
 Risk based dossier assessment approach:
High risk……. Expertise & much time of the assessors will
be spent on rigorous and extensive evaluation of such
products.
Low risk….. Less time & Waiving routine dossier
assessment based on their history of registration and Market in
other countries.
 Fast track designation of priority products:
Fast track products ……HIV/AIDS, Malaria,TB,
Biologics,Vaccine, and RH, Anticancer, Orphan drugs,
and Locally produced medicines.
Fast track medicines will be given priority in Queue.
Non-fast track….. Follow normal line.

Strategic Direction for Dossier Assessment..
 Expedited (Accelerated Procedures):
Abbreviated approval……. Assessment limited to certain
sections of dossier based on evidence of GMP waiver &
availability of market authorization certificate given by
Stringent regulatory authority (SRA)
Collaborative registration….. Products prequalified by
WHO & are under Collaborative registration procedure
(CRP)… focal persons of NRA… confirm sameness of the
submitted dossier with prequalified product.
Conditional approval ….. new chemical entities claimed to
treat seriously debilitating or life-threatening disease, used
emergency situations…designate “priority review”; issue
conditional approval for one year,
Vaccines prequalified byWHO…..Expedited Review

 Stability Requirement:
Climatic Zone for Ethiopia: Zone IVa or Zone Ivb
long term stability study at storage Zone IVb which is
(30oC±2/75%±5%RH) more universal and recommended
byWHO is also acceptable for Ethiopia
Required storage condition for accelerated studies
should be (40oC±2/75%±5%RH).
Required storage condition for long term stability study
for Ethiopia is Zone Iva which is at 30oC±2/65%±5%RH
or 30oC±2/75%±5%RH

 Bioequivalence Requirement:
Strength based and BCS based Biowaiver
FollowWHO Biowaiver guidance
 Products such as tablet, capsule, suspension that are not BCS class
I and Class III require Bioequivalence.
 Products that are used for local or topical action such as ointment,
creams, jells they do not need Bioequivalence study.
 Products whose final preparation is clear solution no need
bioequivalence study as they have almost 100% bioavailability.
 Moreover, products that are classified as BCS Class I and Class III
does not need bioequivalence study for any dosage form is.

Strategic Direction for Dossier
Assessment…
 Authority Implemented Medicine registration information
system (MRIS):
First web-based system in East Africa.
Can be accessed: www.mris.fmhaca.gov.et or
http://mregistration.fmhaca.gov.et/ethiopia.
The application should pass through the online
application and prescreening procedure before the
main review of the dossier.

Medicine Registration Information system (MRIS)

Strategic Direction for GMP inspection
 Risk based cGMP Inspection
 Acceptance of manufacturing facility…. for cGMP based
on the GMP compliance certificate…given
by….Stringent Regulatory (SRA)
 Mutual recognition approach
 Acceptance of manufacturing facility for cGMP
compliance based on the certificate issued by
internationally recognized GMP consulting
organization (e.g.WHO).
 Fast track designation of priority for .....GMP
inspection
 Outsourcing of GMP inspection

Strategic Direction for QualityTesting
 Risk based testing approach
 Waiving pre-market testing as appropriate
 Limiting theTesting Parameter and Critical attributes
based on Risks without compromising Quality
 ConsignmentTesting
 New consignment
 Planned Consignment testing procedure based on
risks.
 Premarket testing for sterile products and local
produced medicines
 Strengthening Pharmacovigilance and Post
Market Surveillance

Medical devices registration requirements
 Types of Medical Devices:
 Accessory: A device that is intended to support,
supplement, and/or augment the performance of one or
more parent devices.
 Parent Device: A finished device whose performance is
supported, supplemented, and/or augmented by one or
more accessories.

Medical devices registration…
• The extent of the requirements of medical device
registration depends on the risk and class of the
device.
• Separate applications and dossiers are required for
each device falling in Class III and above for both
IVDs and non- IVD medical devices.
• Lower class medical devices is acceptable, the
Authority will handled them on a case-by-case basis.

Medical devices registration…
 We follow SRA and non SRA strategy for medical
devices.
 According to the draft medical device MA
strategies, for SRA medical device class III and
above…GMP Waiver is required.
 And for non-SRA class III and above medical
devices,…. site GMP inspection is mandatory.

Documents required for registration
Premarket qualification:
1. cGMP Certificate given by local authority
2. Certificate of compliance:
a. Valid CE certificate
b. Product Standard (ISO certificate)
c. Free sale certificate
d. MA from SRA
3.Agency agreement
4.Product dossier/technical document evaluation….medical
devices classes.
5. Premarket laboratory test (optional)…for sterile MD only

Timeline for processing Medicine Registration Application
Ser. No. Type of Application Timeline
Medicines Approved by SRA
1. New Registration 18 days
2. Re-Registration 2 days
3. Variation 18 days
Medicines Not Approved by SRA
1. New Registration 3 months and 6 days
3. Variation 18 days
FastTrack Medicine Registration Application
1. New Registration 2 months and 11 days
3. Variation 2 months and 11 days

Questionnaires
REGULATIONS AND GUIDELINES
 What are the regulations orthe guidelines of chemical molecules,
and Over the Counters (OTCs) [including website information]?
As of the end of 2017, we are treating all medicine registrations
with one general Medicine registration Guideline. But, following
Expedited medicine registration strategy the old Medicine
registration of 2014 edition has been split into different
medicine registration guidelines. Namely, Guideline for
Registration ofVaccine , Guidelines for Registration of
Biotherapeutic Proteint Products , Guidelines on evaluation of
similar biotherapeutics, Guideline for new molecule medicine
registration, Guideline for Generic medicine registration.
Moreover, the guideline for Low risk (OTC) medicine
registration was planned to be drafted.

Questionnaires
 What are the definition, the procedure, the timeline, and the fee
for approval of new drug applications, hybrid application (like NDA
505b(2) in the USA), and generic drug applications?
Application procedure: Any applicant who is interested to register
his/her medicinal product can apply online through his/her licensed
local agent in Ethiopia. There are different applications pathways
that an applicant can chose from the system (Fast track, SRA and
normal procedure) depending on the type of application.
Regardless of the regulatory pathway one chooses for approval of
an New drug application the EFMHACA standards for the
demonstration of safety and efficacy are same; it is only the source
of information that differs between the paths. The SRA and WHO
medicinal products follow simplified review procedure.

Questionnaires
 Service fee for application of New drug & Generic drug is not
the same.The mode of payment and the stage at which service
fee will be preformed is different ( i.e screening stage, In
depth review stage and QC test stage) . Each application
should be accompanied by a relevant service fee for
registration.Applicants are advised to consult Regulation No.
370/2015 on rate of service fee for food, medicine , health
care professionals and health institution registration and
Licensing council of ministers regulation Number 8729
schedule 8735.
 N.B. In Ethiopia, there is no separate definition for New drug
Molecule and Generic Drug by law , but different service fee
scheme could be applied based on the aforesaid Regulation of
service fee that includes the Bioequivalence study.

Questionnaires
 Does your organization require an applicant as a
local license holder to submit an application in
your country?
An Applicant who is responsible for the product
information is responsible for the submission of
application for registration and there’re should be an
agency agreement between the manufacturer or
the license holder of medicinal product.
 Do you have the accelerated approval process,
priority review process, and streamlined review?
Yes Based on approved Expediting Medicine Market
Authorization Strategy of October, 2017.

Questionnaires
 Do you have the filing review system before main review of the
application?
Yes, but it is not similar to that of US-FDA. In our case, an applicant would
submit its application online; all the required documents should be
uploaded with the application electronically. then the filling review of the
dossier is handled at customer service stage for generic medicines which is
named as dossier screening and the Main review of the dossier would be
handled at the medicine registration and Licensing directorate by medicine
registration and Licensing team. But, for new molecule application; three
stage are required.
1st.Application screening at the customer service stage.
2nd. review and recommendation stage by the Drug advisory committee
(panel review); and
3rd. The in-depth scientific, regulatory, and Quality System review by Drug
assessors and Gmp inspection or GMP inspection waiver on case by case.
 Do you require patent certification for pharmaceutical products?
No

Questionnaires
 What is the regulation or the guideline for labeling for products?
There is no separate Guideline for this, but clearly defined under module 1of
the CTD format Medicine registration Guideline. Under the module I of the
administrative part Medicine registration Guideline 1.7.2. Labeling
(immediate and outer label) described as follows.
Only original labels or computer-ready color-printed labels are accepted for
final approval. In the case where the text of the labels is printed directly on
plastic bottles through a silk screen process, photocopies of these labels will
be accepted for approval.
The titles for batch number, manufacturing, and expiry dates should be part
of the printing (typewritten materials, stickers, etc., are not acceptable). If the
labeling technology of the manufacturer is such that this information is to be
printed on the label during production, a written commitment to show all
the required information on the label of the finished product must be
submitted.

Questionnaires
 Do you have information on each labeling for health
professional and patient?
Yes . Product information including package insert, labeling,
and summary of product characteristics (SmPC) should be
provided in Module 1 of the dossier.All product information
label statements are required to be in English.Any information
appearing in the product information (labels, PIL, and SmPC)
should be based on scientific justification.
Recommended format for the content of the SmPC is
provided in Annex III of medicine registration Guideline.The
applicant is required to provide as per that requirement.

Questionnaires
 What are the regulations or guidelines for stability
and evaluation of safety and efficacy (including
bioequivalence study) for chemical molecules?
There is no separate Guideline for the stability and evaluation
of safety and efficacy of Medicines, but all are included in the
CTD modular format of the medicine registration guideline
currently in use. The same is true for BE. It is treated at the
CTD section 5 of the Module.
 What is the advantage of products (including vaccines)
that they are prequalified byWHO in your country?
Direct registration of such products will be applied. It has a
separate registration route. Hence, it avoid double effort and
we can use assessors to assess other application dossier.

Questionnaires
REQUIREMENTS FOR NEW DRUG APPLICATION/
GENERIC DRUG APPLICATION
 Is it mandatory to submit the ICH CTD (Common
Technical Document) in the application?
Yes
 Is it required to submit a clinical trial (or
bioequivalence study) studied to the local people in
your country?
CurrentlyWe do not require clinical trial (or bioequivalence
study) studied to the local people in your country. It can be
done anywhere in the world specially on similar population in
Africa. Issue of genetic difference should be taken into
account.

Questionnaires
 Is clinical trial or bioequivalence study required
for generic products?
Yes for solid oral generic drugs
 Is it required to get an approval of the protocol
for clinical trials (or bioequivalence studies)
before clinical trials(or bioequivalence studies)
begin?
Yes

Questionnaires
 Are all generic products required to submit
bioequivalence study in generic drug application?
(What are the scopes of products which are
mandatory to submit bioequivalence study?)
 Not necessarily for all.
 Basically, we do have two main options for Biowaiver.
 Biowaiver based on biopharmaceutical classification system
(BCS): Such application is approved based on evidence of
invitro equivalence other than through in vivo equivalence
testing i.e. use of in vitro testing as a reliable surrogate for an
in vivo BE study.
 Biowaivers based on dose-proportionality of formulations

Questionnaires
 What are the criteria for the selection of reference listed drugs in
the bioequivalence study?
It should be the innovator product . Market leading product is also applicable
if justified.
 Do you have regulation and guideline of biowaiver?
Yes
 In case of NTI (NarrowTherapeutic Index), what will be the BE
acceptance criteria? Will it be 90-111.11% as following Europe
guideline instead of 80-125%?
80-125% for the 90% CI for AUC and Cmax is used for all dosage forms.
 Should the batch size of Bio-Batch has to be more than
100,000T? And/or, should Bio-batch has to have identical batch
size as PV batch as described in CTD?
A biobatch should be the greater of 100,000 units, or not less than 1/10th
the proposed production size. A biobatch of < 100,000 units may be
accepted, but then no scale-up is allowed. This should be clearly indicated in
reports for the product, as it affects allowable variations.

Questionnaires
 What are the requirements for registration of
incrementally modified drugs?
We do have guideline for Incrementally modified drugs/ "me-
too" drugs/Biosimilars.
 Do you have any officially acceptable pharmacopoeia
(eg.European Pharmacopoeia, British Pharmacopoeia,Korean
Pharmacopoeia) ? If so, what kind of dossier would be waived?
European Pharmacopoeia, British Pharmacopoeia,USP and Japanese
pharmacopeias are recognized official pharmacopias in Ethiopia.There is
no procedure for dossier waiver as of today, but following the Expediting
Medicine Market Authorization Strategy of October 2017, work is under
way for low risk medicinal products.
 Is it required to submit sample product for New Drug
Applications, hybrid application (like NDA 505b(2) in the USA),
and generic drug applications?
Not necessarily, but for sterile formulation for the Quality test purpose.

Questionnaires
 What are the requirements of stability data for new
drug applications, hybrid application (like NDA 505b(2)
in the USA), generic drug applications, and Over the
Counters (OTCs) applications?
 Selection of the batch, testing frequency, storage condition,
minimum tested period for the long-term test and the
accelerated test
 The medicine registration guideline defines the stability data package for
active pharmaceutical ingredients (API’s) and Finished pharmaceutical product
(FPP) that is sufficient for a registration application within Ethiopian Market.
The study condition should be as per ICH Guideline for zone IVb.Alternative
approaches can be used when there are scientifically justifiable reasons.
 The minimum data required at the time of submitting the dossier (in general)
are

Questionnaires
Storage temperature (ºC) Relative humidity (%) Minimum time period
(months)
Accelerated 40±2 75±5 6
Intermediate * * *
Long-term 30±2 65±5 or 75±5 6
 There is no separate provision for New drug applications,
Generic application or OTC. The same requirement
applies for all formulation as long as stability study is
concerned.

Questionnaires
Post-approval Change
 What are the regulations or the guidelines of post-
approval change?
 Please consult www.fmhaca.gov.et/ for post –approval change
 What is the requirement of dossiers by variation
category (eg. addition of API manufacturing site)?
 Conditions to be fulfilled
 1.The new manufacturer has approved for GMP by NDA for
manufacturing of API concerned.
 2.The specifications (including in-process controls, methods of
analysis of all materials), method of preparation (including batch
size) and detailed route of synthesis are identical to those
already filled in the registered product.

Questionnaires
 Where materials of human or animal origin are used in the
process, the manufacturer does not use any new supplier for
which assessment is required of viral safety or of compliance
with the current WHO Guidelines on transmissible
spongiform encephalopathies in relation to biological and
pharmaceutical products.
 Documentation
 1.A complete 3.2.S section of the dossier as per EFMHACA
Guideline for Registration of Medicines.
 2. A declaration from the supplier of the registered FPP that
the route of synthesis, quality control procedures and
specifications of the API and key (ultimate) intermediate in the
manufacturing process of the API (if applicable) are the same as
those already filled during registration.

Questionnaires
 Either a transmissible spongiform encephalopathy (TSE) European
Pharmacopoeia certificate of suitability for any new source of
material or, where applicable, documentary evidence that the specific
source of the material that carries a risk ofTSE has previously been
assessed by the competent authority and shown to comply with the
current WHO Guidelines on transmissible spongiform
encephalopathies in relation to biological and pharmaceutical
products.To include BSE.
 Batch analysis data (in a comparative tabular format) for at least two
(minimum pilot scale) batches of the API from those filled during
registration and proposed manufacturers/sites.
 The application should clearly outline the “registered” and
“proposed” manufacturers.

Questionnaires
Renewal
 What are the scope, cycle, and requirement of renewal
for the approved products, (including abbreviation form
of renewal)?
The renewal is applicable for both the GMP inspection certificate
and already registered products.
 The renewal cycle is every 4 year.
 Any technical documents shall not be requested upon re-
registration; unless change is declared by the pharmaceutical
manufacturer or change is identified by the Authority during
application reviewing in the MRIS. But all necessary administrative
documents such as cGMP compliance status shall be submitted. If
variation is declared during the re-registration application, the re-
registration process will be treated by the variation guideline of
the Authority.

Questionnaires
 What is the advantage of the certificated PIC/S
(Pharmaceutical Inspection Convention and
Pharmaceutical Inspection
Cooperation/Scheme) of Korea?
We recognize EU-GMP, US-FDA,WHO, PIC/S.
Moreover we can have Mutual agreement through
signing of MOU.

Questionnaires
 Is it required to inspect manufacturing site for generic drug
application or Over the Counters (OTCs) applications? Are there
any checklists for GMP inspections?What is the timeline for
GMP inspection?
 In Ethiopia the GMP inspection procedure is somewhat different from
other countries.
 It is not specifically linked to each product type, but line based inspection
would be followed for sites which inspected by the inspector of the
Regulatory Authority.
 On the other had we do have GMP inspection waiver option based on the
GMP inspection history of the manufacturing facility for the line based or
product based byWHO listed stringent regulatory Authorities.We have
also a GMP inspection waiver option forWHO prequalified products.
 The checklist is part of the GMP inspection Guideline currently in use by
EFMHACA.

Questionnaires
OTHER POLICY
What is the regulation of the pricing for New
Chemical Entities?
 There is no price regulation for all types of medicines.
 Ethiopia does not have price policy
Free Market Economy system
 In our revised (but not yet approved proclamation), an
article which obliges manufacturers to put retail price
on secondary pack of medicines.

Website: www.fmhaca.gov.et

Gamsahamnida!!!
አመሰግናለሁ!!!
Thank you!!!

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