203 - Unit 4

Afro-Asian countries-A brief

introduction
 Licensing procedures in African Countries
All countries in Africa (except Sahrawi Republic), have National Medicines
Regulatory Authorities (NMRAs) but their organizational set-up and
functionality are variable. Some are located within Ministries of Health and
others are semi-autonomous.
No medical products are permitted to be sold in any country unless these
products have been approved by the respective NMRAs. The core NMRA
functions include: marketing authorization (MA); licensing of manufacturing
establishments; imports and export control; inspection of manufacturing
premises and distribution channels; market surveillance (product quality
monitoring, pharmacovigilance, control of drug promotion and advertising);
quality control; and oversight of clinical trials on drugs.
The country wise list of NMRAs is shown in below:
 South Africa

• South Africa is the largest market in African region. The Medicines and
Related Substances Act in South Africa, provides for the:
Establishment of the South African Health Products Regulatory Authority
(SAHPRA),
Chief Executive Officer and staff of the Authority
Registration of medicines, medical devices and in vitro diagnostic medical
devices,
Transitional measures and matters connected therewith
 Review pathways
An evaluation will follow one of the following review pathways:
Full review
Abridged review
Verified review
Recognition Review pathways, represent reliance-based evaluations.

The World Health Organization defines reliance as “The act whereby the
regulatory authority in one jurisdiction may take into account and give
significant weight to i.e. totally or partially rely upon evaluations performed by
another regulatory authority or trusted institution in reaching its own decision.
The relying authority remains responsible and accountable for decisions taken,
even when it relies on the decisions and information of others.”
Two additional procedures can be used for reliance/ collaborative review,
which are not strictly regulatory authorities:
World Health Organization Prequalification (WHO PQ)
Zazibona collaborative procedure.
The electronic submission also has to comply with the validation criteria for
eCTD or eSubmission.
The submission has to be accompanied by proof of payment of the screening
(validation) and application fees, medicine sample and copy of the certificates
of analysis (CoAs) of the batch of active pharmaceutical ingredient (API) used
to manufacture the medicine sample and the final product.
Following successful administrative screening the application will be imported
into the system for technical validation. The registration process can take many
years with an estimated average of about 36 months. Applicants will be kept
informed of their application’s status via an online tracker, which will be
updated when an application passes screening.
If the deficiencies are regarded reparable, the recommendations are sent to
the applicants. The applicant should preferably respond to recommendations
on all aspects in one electronic sequence. Previously, a period of three
months for pharmaceutical recommendations and six months for clinical
evaluations was allowed for the applicant to respond.
In order to speed up the process, a period of three months is being
considered. Post approval variations: SAHPRA adopted the EU variation
classification guidelines for orthodox human and veterinary medicines in full
in an effort to harmonize medicine policies and procedures with those of the
EMA which are in turn aligned to ICH.
Renewal: In South Africa the product registration (or marketing
authorization) is valid for five years under the Medicines and Related
Substances Act after which time it should be renewed if so required by
Authority or the Director-General of Health.
 Different marketing authorization routes
• Chemical drug registration classification is divided into innovative drugs, improved new drugs,
generic drugs, drugs approved in oversea.
• The chemical drug registration is classified into 5 categories as below:
• Class I: Innovative drug not licensed globally, it refers to chemical compound with novel and
clear chemical structure and with pharmacological effect and clinical value.
• Class II: Me-better new drug not licensed globally, it refers to drugs with obvious clinical
strength and the structure, dosage form, formulation, manufacturing, the route of
administration or indication is/are optimized based on well-known active pharmaceutical
ingredient.
• Class III: The copy of originator drug licensed outside of China but not in China by local
applicant, the copy drug should be aligned with originator product in quality and efficacy. The
strength and the dosing can be different from the original if there is sufficient data to support.
• Class IV: The copy of originator product licensed in China, the copy drug should be aligned
with originator product in quality and efficacy.
• Class V: Application for China marketing authorization approval for drug licensed outside of
China.
• Other changes that need to be filed on record as stipulated by NMPA
Variations to be reported in Annual Report:
oMinor changes in drug production process;
oOther changes that need to be reported as stipulated by NMPA.
For a supplementary application filed after the drug is marketed, if
verification or inspection is required, it shall be implemented with reference
to the procedures for drug registration verification or inspection specified in
Drug Registration Regulation.
Renewal The Marketing Authorization for drugs is valid for five years from
the date of issuance. Compared with the first registration, the renewal process
and application dossier are simpler.
Generally, the NMPA can complete reviewing the renewal application and
issuing the new Marketing Authorization in 5-6 months.
 Post approval variations
The application for partial changes (variations, changes and amendments) can be
made at any time during the granted period.
The most common reasons for applying for variations, changes and amendments
in an existing Marketing Approval are:
Changes of excipients and/or their contents
Change of manufacturing methods of active pharmaceutical ingredient and/or
finished product
Change of specifications and test methods of active pharmaceutical ingredient
and/or finished product
Addition of new indications in parallel with addition of dosage for the new
indications
• Different marketing authorization routes Depending on the dossier types, the
evaluation of new medicinal products can go through one of the 7paths ranging
from 7 to 300 working days.
• In addition, the drug submission is divided into the below categories in
Indonesia: new drug registration (including new biological products, and
generics/copy drugs), registration variations, and renewal registration, which
are divided into 7 categories:
Category 1: Registration of New Drugs and Biological Products, including
Biosimilar Products.
Category 2: Registration of Generic Drugs and Branded Generic Drugs
Category 3: Registration of other preparations containing Drugs with special
technology, such as transdermal patches, implants, and beads
Category 4: Major variations Registration
Category 5: Minor Variations Registration with approval
Category 6 : Registration of Minor Variation by Notification only
• Review Process
The submission to NADFC must be in dossier in CTD format and the types of documents required
are different depending on the classification. After getting HPR approval, then there is a maximum
1 year period to proceed Registration :
 Post approval variation
In general, the drug registration (also known as marketing authorization submission)
is classified into 6 categories.
The registration of variations falls under category 4 to 6 and they are defined as
follows:
• Category 4: is Registration of Major Variation (VaMa). If request for Category 4
(VaMa) related to quality variation, and which is considered in need for a clinical
trial, then it has to go with the Pre registration procedure.
• Category 5: is Registration of Minor Variation which needed approval (VaMi-B)
• Category 6: is Registration of Minor Variation by Notification only (VaMi-A).
The applicant needs to submit the notification of self-accessible changes or minor
variations (Tell and Do” changes) to NADFC after having a direct discussion with
NADFC’s evaluator. It should be submitted only if there is no impact in terms of
safety, efficacy, and quality matters.