Generic Drug Registration Requirements in Row Countries

Abstract

The regulatory requirements of several countries of the world vary from each other. Therefore, it's challenging for the companies to develop one drug submitted by the countries for approval. The regulatory strategy for product development is crucial to be established before developmental work to avoid significant surprises after applying. The crucial role of the regulatory authorities is to ensure the quality, safety, and efficacy of all medicines in circulation in their country. One of the primary challenges for regulatory authorities is to make sure that the pharmaceutical products are developed as per the regulatory requirement of that country. Product registration within the rest of the world could also be challenging because the regions thereunder aren't harmonized. This region comprises mainly Asia Pacific, Latin America, Eastern Europe, Africa, and Gulf countries.

Full text

Generic Drug Registration Requirements in Row Countries
Dr. Shailaja Pashikanti*, Nirupama Koribilli
Department of Pharmaceutical Management and Drug Regulatory Affairs,
Andhra University, Visakhapatnam-530003
dr.pshailaja@andhrauniversity.edu.in
Abstract The regulatory requirements of several countries of the world vary from each other. Therefore, it's challenging for the
companies to develop one drug submitted by the countries for approval. The regulatory strategy for product development is
crucial to be established before developmental work to avoid significant surprises after applying. The crucial role of the
regulatory authorities is to ensure the quality, safety, and efficacy of all medicines in circulation in their country. One of the
primary challenges for regulatory authorities is to make sure that the pharmaceutical products are developed as per the
regulatory requirement of that country. Product registration within the rest of the world could also be challenging because
the regions thereunder aren't harmonized. This region comprises mainly Asia Pacific, Latin America, Eastern Europe,
Africa, and Gulf countries.
Keywords: Generic, Global, Regulatory, Registration, Row Countries
INTRODUCTION
GENERIC DRUG MARKET
A generic drug is a pharmaceutical product that is usually
defined as interchangeable with an innovator product
manufactured and marketed after the expiry date of the
patent or other exclusive rights. [1]
Generic drugs are marketed under an approved name or
non-proprietary other than a proprietary or brand name.
They're less expensive than brand-name drugs. Due to
their low price, generic drugs are often the sole medicines
that the poorest can access.
https://www.who.int/medicines/areas/access/NPrices_Glo
ssary.pdf
The global generic drugs market reached a worth of US$
386 Billion in 2020. The global market for generic drugs
should grow from $411.6 billion in 2020 to $650.3 billion
by 2025, a compound annual growth rate (CAGR) of 9.6%
for 2020-2025. https://www.h.cobccresearcm/market-
research/pharmaceuticals/generic-drugs-markets-
report.html
The significant factors contributing to the growth of the
generic drugs market include the increasing prevalence of
chronic diseases, diabetes & cardiovascular diseases,
growth in the geriatric population, increasing high demand
for generic medicines, healthcare expenditure, and a large
number of patent expired branded drugs. However,
stringent governmental regulations and adverse effects
associated with drugs are expected to restrain the market
development. The rising demand for newer versions of
generic drugs, different clinical trials, and large numbers
of licensing & partnering strategies to launch new
products by key vendors contributes to significant demand
for generic drugs.
https://www.alliedmarketresearch.com/generic-drugs-
market
ROW COUNTRIES:
This region comprises mainly the countries from the Asia
Pacific, Latin America, Eastern Europe, Africa, and Gulf
Countries While countries from the Asia Pacific and Gulf
have almost harmonized their regulatory environment
through The Association of Southeast Asian Nations
(ASEAN) and Gulf Co-operation Council (G.C.C.)
organizations, the remainder of the regions are yet to
return up with the harmonized regulations in their
respective regions. a positive regulatory environment in
these countries has also allowed easy entry of foreign
companies.
In the ASEAN regions, the applicant can suit the standard
requirements set within the ASEAN Common Technical
Dossier (ACTD) to urge approval within the member
countries (Indonesia, Malaysia, Philippines, Singapore,
Thailand, Brunei, Myanmar, Cambodia, Laos, and
Vietnam). Almost identical documents are often used for
national approval within the non-member countries of the
Asia Pacific region with simple amendments.
https://www.fda.gov.ph/wp-
content/uploads/2021/03/ASEAN-Common-Technical-
Dossier-ACTD-December-2016-from-ASEAN-
Secretariat.pdf
DRUG FILING REQUIREMENTS IN SOUTH
AFRICA: http://www.santr.gov.za/
South Africa's pharmaceutical market is one of the main
attractive markets in Africa. Most of the local drug
manufacturers and distribution are within the hands of
major international Pharmaceutical Firms. GBI Research
valued South Africa in the pharmaceutical market at $ 7
Billion in 2018 and expects it to achieve $14 billion in
2023 at a Compound Annual Growth Rate (CAGR) of
6.8%
http://www.pharmabiz.com/NewsDetails.aspx?aid=85525
&sid=21
South African Development Community (SADC) was
established in 2002 as a part of the Pharmaceutical
Programmer under the SADC Secretariat's Directorate of
Social and Human Development and Special Programmer
(SHDSP). Currently, SADC features a membership of 15
Member States, namely: Angola, Botswana, Democratic
Republic of Congo (D.R.C.), Lesotho Madagascar,
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Malawi, Mauritius, Mozambique, Namibia, Seychelles,
South Africa, Swaziland, United Republic Of Tanzania,
Zambia, and Zimbabwe. The foremost objective was to
harmonize pharmaceutical trade and regulation. Though
some activities are ongoing to date, each country follows
its regulations.
https://www.mea.gov.in/Portal/ForeignRelation/southern-
african-development-community-cooperation-april-
2012.pdf
FEES:
1. Generic products (pharmaceutical, analytical and
bioavailability evaluated) Rs 25000 per application.
2. Strengths and dosage form other than those referred
above: Rs 8500
3. Screening fee on receipt of an application: Rs 1500
4. Generic products with clinical data: Rs 40 000
5. Inspections
(a) Local manufacturing sites: Rs 600 per hour.
(b)International manufacturing sites: Rs 3600 per
hour.
6. New Chemical Entities – Rs 45000 per application
Drug registration specific requirements for South
Africa:
 Quantity of samples: lowest pack size of minimum
100 units with minimum one-year validity
 CoPP authenticated by South African authority is not
needed
 The notary is not needed
 Separate dossiers for different strengths
 Three pilot batches stability data (ACC-
400C/75%RH, LT-250C/60%RH but 300C/75%RH is
also acceptable)
 Stability studies must include microbial test
 Working standard sample is to be sent
 Process validation protocol is compulsory
 The label of the product should possess the schedule
of the medicine
 The Patient Information Leaflet (PIL) should be in
English and one other official language (Portuguese,
Arabic etc.)
 IR spectra compulsory for the container closure
system
 All the units must be in SI units
 The frequency of in-process quality control should be
included
 Stringent limits for dissolution, stability release
 GMP certification is valid for 2 years, and it is not
product-specific
MEDICINES CONTROL COUNCIL
The drug regulatory authority of South Africa is that the
Medicines Control Council under the Ministry of Health.
The registration of medicine was governed by the
provisions and requirements of the Medicines and Related
Substances Control Act No. 101 of 1965 to manage all
aspects of the Manufacturing, marketing, and sale of
medicines for human, veterinary use, biological products,
and medical devices. South Africa is additionally
modernizing its regulatory structure to hurry up drug
approvals. to this end, the government established the
South African Health Products regulatory agency
(SAHPRA) to exchange the Medicines Control Council
(MCC). http://www.mccza.com/
The new body will have an honest range of
responsibilities, including helping to urge obviate the
backlog of drug applications and speed up the registration
process from five years at present to a minimum of one
year. South Africa has taken positive steps to strengthen
macroeconomic growth, including pushing for the
country's official designation as a BRICS (Brazil, Russia,
India, China, and South Africa) nation.
DRUGS REGISTRATION PROCEDURE [2,3]
REGISTRATION OF DRUGS:
The Proposed Holder of the Certificate of Registration
(Phcr) is Eligible to launch the product within the market.
The application submitted should be signed by the
pharmacist authorized to talk with the council [4]. This
pharmacist should be within the full-time employ of the
company. The general format for the dossier is CTD. The
approval process for both a replacement drug and a
generic is that equivalent. The applicant must provide
evidence that the product features a comparable
therapeutic effect of the originator's product for generic
medicines.
http://old.sfda.gov.sa/En/Drug/Topics/Regulations+-
+Guidelines.html
This can be done by performing comparative clinical trials
or providing proof of bioequivalence, or in some cases, by
laboratory testing. In June 2010, the Medicines Control
Council (MCC) announced implementing the South
African Common Technical Document (ZA CTD) format
from June 1, 2011, which replaced the MRF1. The new
strategy to implement the eCTD format for dossier
submission is ongoing, and it's mandatory from June 1,
2014.
http://www.rrfa.co.za/wpcontent/uploads/2012/11/CTD-
implementation-road-map-Feb16-v6.pdf
DRUG FILING REQUIREMENTS IN NIGERIA
The local pharmaceutical Manufacturing industry is
currently able to meet 25 percent of local demand.
Nigerian manufacturers produce liquid preparations,
tablets, capsules, ointments, lotions, creams, and
ophthalmic preparations. The local pharmaceutical
industries can meet domestic demand for some classes of
medicines. The remaining 75% of the market is
increasingly dominated by imports from Asian companies.
Business Monitor International (B.M.I.) analyzed that
Nigeria will earn $9.61billion from the pharmaceutical
industry by 2025. Growth in the pharmaceutical market is
expected to be driven by the increasing availability of
low-cost generic drugs.
https://pharmexcil.com/docs/DRProcedures/NIGERIA/Ar
egprocedure_nigeria.pdf
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NATIONAL AGENCY FOR FOOD AND DRUG
ADMINISTRATION AND CONTROL (NAFDAC)
http://www.nafdac.gov.ng/
The drug regulatory authority of Nigeria is the National
Agency for Food and Drug Administration and Control
(NAFDAC) under the Federal Ministry of Health, is
responsible for regulating and controlling the
manufacture, importation, exportation, advertisement,
distribution, sale, and use of food, drugs, cosmetics,
medical devices, chemicals, and pre-packaged water.
PROCEDURE:
There are different steps each imported product must pass
to get a license number.
STEP 1:
The applicant has got to register the name at the Ministry
of Commerce in Nigeria. This brand name is the
applicant's choice, and the sole criteria are it shouldn't
infringe other brand names within the market. Then the
applicant must undergo the Registration Division,
NAFDAC, a written application, stating the
manufacturer's name, generic name (brand name),
strength, indications, and acquire the prescribed
application form, which must be crammed adequately
with all information required. This form, labeled "FORM
D- R.E.G./001," shall be obtained on payment of N500.00
per product. A separate form shall be submitted for every
drug product (means a separate drug formulation).
However, the application for registration of 1 dosage form
with different strengths could also be made on an
equivalent form. [5]
STEP 2:
The necessary documents described by NAFDAC to
register each product must be found satisfactory before
any other process can be carried out. If the documents
comply with the NAFDAC requirements, a permit to
import samples of products is equipped for the applicant.
The applicant must import specified samples to be used
for vetting and laboratory analysis (National Chemical
Laboratory).
STEP 3:
At this stage, samples of products presented are vetted,
which incorporates checking the labels, leaflets, drugs
information. There are minimum requirements for product
labeling like name of the drugs name, name and address of
the manufacturer, production and expiry date, batch no,
and so on.
Documents to be submitted during the vetting are:
1. Copies of import permit and receipt of payment.
2. Dossier consistent with NAFDAC format for drugs.
3. Samples for every product.
4. Letter of invitation for inspection.
5. Compressive Certificate of study.
STEP 4:
After the vetting is completed, the applicant is required to
bring some samples for lab analysis. Submit specified
quantities of sample products alongside copies of the
receipt for the processing fee and application letter for the
submission of samples. Then product(s) go to the lab for
analysis to make sure compliance with standard
specifications.
STEP 5
At this stage, decisions are taken whether the product
qualifies to tend NAFDAC registration number or not. If
the product meets all the wants, a registration number is
issued. Once the merchandise is given a registration
number, the applicant has to collect the notification
number, pay the required amount for the license
certificate, and present the receipt to urge the notification.
Now the applicant is qualified to import the product
certificate lasts for 5 years.
http://pharmabiz.com/Services/ExportImport/Countries/Ni
geria.aspx
FEE:
 The registration form per drug product is five hundred
nairas (N500:00).
 Registration form for other regulated products is two
hundred and fifty nairas only (N250:00)
 Change of source for drugs to different manufacturer
POM- N 250,000:00 + 5% VAT,OTC- N 1,
000,000:00 + 5% VAT
 Change of source for drugs to same name
manufacturer POM- N150, 000:00 + 5% VAT,OTC-
N 250,000:00 + 5% VAT
 Processing fee per regulated product for all additional
sites belonging to same name corporation is one
hundred and fifty thousand nairas only plus 5%
VAT(N=150,000:00 + 5% VAT)
Note:
 Failure to respond promptly within 30 workdays to
queries or inquiries raised by NAFDAC on the
application will automatically lead to suspension of
further processing of the application.
 The registration time line after submission of vetting
samples is a hundred (100) workdays.
DRUG FILING REQUIREMENTS IN SRI LANKA
Sri Lanka is an emerging dharma market, and the market
size is estimated to be around $400 million. The
pharmaceutical industry is dependent upon imports. There
is no essential drug production in the country.
COSMETICS, DEVICES AND DRUGS
REGULATORY AUTHORITY (CDDRA)
CDDRA is the drug regulatory authority of Sri Lanka
under the Ministry of Health framed to regulate and
control the manufacture, import, sale, storage and
distribution, recall of Cosmetics, Devices, and Drugs
(including nutraceuticals and borderline devices)
efficiently and effectively to ensure rational use. The
Cosmetics, Devices & Drugs (C.D.D.) Act No. 27 of 1980
is the legislative framework that provides the legal
authority to regulate CDD in Srilanka.
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https://pharmexcil.com/uploads/countryreports/Sri_Lanka.
pdf
REGISTRATION OF DRUGS:
There are no stringent regulations for getting market
authorization in Sri Lanka. The dossier requirements are
given to the manufacturer in a guidance document via an
authorized local agent. The approval process for both a
new drug and a generic is the same. In the case of
generics, the bioequivalence study data is not required to
be submitted. Only permission to import the drug to Sri
Lanka is needed. The import is based on the necessity of
the medicine in the country, which the State
Pharmaceuticals Council decides by preparing Essential
Medicines List and then informs to CDDRA.
http://nmra.gov.lk/
INFORMATION REQUIRED FOR REGISTRATION
OF A DRUG
Submitted as a word document and will contain all
requirements as laid out in Form A- Schedule IV.
1. Name of the applicant
2. Address
3. Status of applicant
• Manufacturer
• Importer
If the applicant is an Importer, the name and address of
the manufacturer must tend.
1. Name of the drug
2. Name (if any)
3. Official or approved name indicating the regulatory
body that has given the name(whether B.P., U.S.P.,
etc.)
4. Composition
5. All ingredients, active and inactive, should be listed
by their official or approved names and will include
their exact quantities as per unit dose or, if it's not
practical, as a percentage of the entire formulation.
6. Main pharmacological class and ATC-class (if
known) to which the drug belongs.
7. A certificate from the Health authorities of the
country during which it's produced, confirming that
the drug is in use there and therefore the period of use
and, if not, the reason for not marketing it within the
country of origin (Free Sale Certificate, Certificate
consistent with the WHO Certification Scheme on
Pharmaceutical Products occupation International
Commerce- the recommended format should be
used.)
8. Published reports on controlled clinical trials-
establishing the therapeutic efficacy of the drug.
(Uncontrolled studies would be accepted as long as
controlled clinical trials aren't necessary to prove
efficacy). Within the case of combination drugs, the
evidence must be provided to justify the inclusion of
all the active constituents within the formulation.
9. Summary of toxicity tests for teratogenicity indicating
the security of the drug
10. Datasheet giving the subsequent
A. Pharmacology
 Pharmacological actions
 Mechanism of action (if known)
 Relevant pharmacokinetic data
B. Clinical information
 Indications
 Contraindications
 Precautions [6]
The Processing fees at present are:
 New Chemical Entities for Sri Lanka (NCE) - Rs.
50,000/= + VAT
 New Dosage form application for Sri Lanka (NDF) -
Rs.25,000 /= + VAT
 New fixed dose combination products (NFDCs) -
Rs.50,000 /= + VAT
 New product of existing drugs - Rs.10,000 /= + VAT
 Re-registration application - Rs.10,000 /= + VAT
DRUG FILING REQUIREMENTS IN GCC: [7, 8]
The Gulf Cooperation Council (G.C.C.) is additionally
referred to as The Cooperation Council for the Arab States
of the Gulf. The member states of G.C.C. are Bahrain,
Kuwait, Oman, Qatar, Saudi Arabia, United Arab
Emirates, and Yemen as members in Health Council).
G.C.C. Pharmaceutical Industry report (March 31, 2020)
says that the G.C.C. pharmaceutical industry is predicted
to experience sustainable growth in the medium to future.
Increased domestic production, foreign investments, and
generics consumption are likely to support the market's
evolution. This market is overgrowing and is predicted to
succeed in around 3 billion USD by 2020. According to
the latest report given by IMARC Group, the G.C.C.
generic drugs market size reached US$ 3.94 Billion
in 2020. Saudi Arabia leads overall annual drug spending
at more than $2.8bn, followed by the U.A.E. at $1.8bn,
and Kuwait at $374m. Qatar, Oman, and Bahrain imitate
at $227, 152, and 118m, respectively. Many analysts
expect the Emirates' annual drugs spend market size to
succeed at $9.7bn by 2025, with a per capita spend of on
the brink of $500. The G.C.C generic drug market reached
a value of US$ 3.94 Billion in 2020.
https://www.giiresearch.com/report/imarc1006971-gcc-
generic-drug-market-industry-trends-share-size.html
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PROCEDURE FOR GCC-DR:
In 1999, a pharmaceutical harmonization initiative was
launched by a committee called Gulf Central Committee
for Drug Registration(GCC-DR), with the executive office
being located in Riyadh, Saudi Arabia.
https://ur.booksc.eu/book/39954826/1c1a3d
The main objective of the GCC-DR is to coordinate health
policies and programs among the participating members
via the exchange of information, knowledge, techniques,
and expertise. It is responsible for the registration of
pharmaceutical products, GMP inspection and
compliance, approval of quality control laboratories, and
review of technical and post-market surveillance reports.
The GCC-DR adopted the ICH guidelines as a primary
source for developing its own. It follows a centralized
procedure for drug registration with harmonized drug
registration requirements and drug pricing for all the
member states. After centralized approval of product,
authentication and fee payment should be followed in
each member state as per their local policies. By 2006,
submission of application to the GCC-DR had become
mandatory for most of the pharmaceutical classes. Most of
the companies taking this routeing model their dossiers on
the standing requirements of Saudi Arabia. Most
companies reported that registration through the
centralized system took longer than through the national
procedure. The registration process of pharmaceutical
products depends on two licenses: one for the company as
a whole and the other specific to the product. In Saudi
Arabia, Oman and Yemen, company registration must be
approved before product registration, whereas in Kuwait,
Qatar, UAE, company and product registration processes
can be filed in parallel.
DRUG FILING REQUIREMENTS IN SAUDI
ARABIA
Saudi Arabia is predicted to maintain its position because
the largest pharmaceutical market within the Gulf,
consistent with the G.C.C. Pharmaceutical Industry report.
Saudi Arabia represents 65% or $7.1 billion of the
pharmaceutical market within the member countries of the
G.C.C.
According to Espicom, Saudi Arabia's pharmaceutical
market "is expected to rise by a CAGR within the high
single digits during 2017-2021." The drug company in
Saudi Arabia with the most significant share of the
pharmaceutical market in-country is G.S.K. However,
most of the local production is predetermined for the
export markets. Domestic production accounts for around
15 percent of the general supply of pharmaceuticals within
the market. Around 15-20 pharmaceutical manufacturers
are operating within the Kingdom, including indigenous
companies and subsidiaries of multinational
pharmaceutical giants. https://www.oatext.com/future-of-
the-pharmaceutical-industry-in-the-gcc-countries.php
SAUDI FOOD AND DRUG AUTHORITY
The primary regulatory agency in Saudi Arabia is that the
Ministry of Health. Therefore, the Saudi Food and Drug
Authority was established in 2003 to be liable for
developing and enforcing the regulatory system. The most
purpose of the SFDA establishment is to manage, oversee,
and control food, drug, medical devices and set mandatory
standard specifications thereof, whether or not they are
imported or locally manufactured. The control and testing
activities are often conducted within the SFDA or other
agencies ' laboratories. https://old.sfda.gov.sa/en/about
REGISTRATION OF DRUGS:
SFDA published draft guidelines on the official website
guiding the procedure and requirements for filing
generics. Pharmaceutical products are required by law to
be registered before marketing. This applies to both
locally manufactured and imported products. Foreign
manufacturers must be represented by local agents. the
entire dossiers are sent to the Department of registering
human medicines.
Application for Company
registration
Administrative registration
Approval of Company
Registration
Review of the dossier
Application for product
Product classification
Sample analysis
Pricing
Approval
Apply for other member states
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 Drug Application
 Fill and export the application for module 1
 Pay the application fee.
 Submit the dossier.
 Receive and answer assessment inquiries
 RFI
 Receive the application review decision.
 Print the registration certificate.
 Manage the drug file life cycle.
https://pharmaknowl.com/sfda-drug-registration-
requirements-approval-process
CONCLUSION
Medicine regulation may be a legislated function of any
regulatory agency in a country. As such, the authority is
accountable to the country's citizens regarding the supply,
efficacy, quality, and safety of medicines. Across most
regional pharmaceutical markets, generics are emerging as
solid challenges to branded medications. Such robust
expansions are attributed to the soaring demand for
pharmaceutical products and energy to scale back the
health care cost, at constant time, efforts by health plan
providers to regulate spending on costly prescribed drugs,
providing a lift to the drug industry.
REFERENCES:
1. Swetha Handoo, Vandana Arora, Deepak Khera.A comprehensive
study on regulatory requirements for developing and filing generic
drugs globally 2012 Jul-Sep; 2(3): 99–105. DOI: 10.4103/2230-
973X.104392
2. B. Jayalakshmi, R. Seetharaman, R. Kamaraj. Registration and
Regulatory Requirements of Generic Drugs Marketing
Authorization in "BRICS" Countries. Research J. Pharm. and Tech.
2019; 12(3): 1403-1408. DOI: 10.5958/0974-360X.2019.00234.8
3. Senthil V, L. Srianitha R. Baviyapriyadharshini. Regulatory
Requirements For Drug Products Registration In South Africa
February 2018 International Journal of Drug Regulatory
Affairs 3(4):1-8 DOI:10.22270/ijdra.v3i4.171
4. Adrea Keyter, Joey Gouws, Sam Salek, Stauart Walker. The
Regulatory Review Process in South Africa: Challenges and
Opportunities for a New Improved System Ther Innov Regul Sci
2018 Jul; 52(4): 449–458.Published online 2018 May30. DOI:
10.1177/2168479018776649
5. Nandini Warier, Priti Mehta. Comparative Study of Generic Drug
Registration Requirements for Dossier Submission in African
Region-Kenya, Ghana, Nigeria, and Botswana Volume 3 , Issue 2 ,
2016. DOI : 10.2174/2213476X03666160605111335
6. D. Thambavita, P.Galapptthy, R.L.Jayakody. Regulatory
requirements for the registration of generic medicines and format
of drug dossiers: procedures in Sri Lanka in comparison with
selected regulatory authorities. Journal of pharmaceutical policy
and practice 11, Article number: 14 (2018)
7. Jitendra Kumar Badjatya, Journal of Drug Delivery &
Therapeutics.Overview of Drug Registration Requirements for
Pharmaceuticals in Emerging Market2013, 3(2), 227-232
DOI https://doi.org/10.22270/jddt.v3i2.466
8. S. Pateriya et. Regulatory Aspects of Pharmaceuticals’ Exports in
Gulf Cooperation Council Countries J Young Pharm2011 Apr-Jun;
3(2): 155–162.DOI: 10.4103/0975-1483.80305
Shailaja Pashikanti et al /J. Pharm. Sci. & Res. Vol. 13(10), 2021, 617-622
622