Drug Approval Manuscript India PDF
Drug Approval Manuscript India PDF
Abstract:
In the Current scenario, different countries have to follow different regulatory requirements for marketing authorization
application (MAA) approval of new drug. In this present work, we studied the drug approval process and regulatory
requirements according to US Food and Drug Administration (UDFDA), European Medical Agency (EMA) and Central Drug
Standard Control Organisation (CDSCO).
Key Words: Drug Approval, Regulatory Requirements, USFDA, EMA, INDIA
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Yes
Send to reviewer
+ve
Applicant submit amended Review report
application to FDA and FDA
review the amended -ve
Refused to applicant
FIGURE 2: Drug approval process in USA
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Centralized Procedure and is for five years, however, the extension can be applied
The Committee for Human Medicinal Products (CHMP) to the EMEA three months before the expiration of this
evaluate the applications received by the EMEA. In view of period. FIGURE 3 represent the centralized procedure for
the applicant's preference, CHMP contracts out assessment marketing authorization.
work in one of the member states (the "rapporteur"). After Centralized process is compulsory for:
the complete assessment, the CHMP deliver opinion to EU Those medicines which are derived from any
Commission within 210 days [11]. The EU Commission biotechnology processes, such as genetic
requests comments from other member states, if a positive engineering.
opinion from CHMP is received. The other member states Those medicines which are intended for the
can respond in about 28 days. When a licence is treatment of Cancer, HIV/AIDS, diabetes,
recommended, a European Public Assessment Report neurodegenerative disorders or autoimmune
(EPAR) is produced and marketing authorisation is issued. diseases and other immune dysfunctions [12].
This authorisation is valid throughout the European Union
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Medicines officially designated 'Orphan product characteristics, labelling and package leaflet within
medicines' (medicines used for rare diseases). 120 days. This report can be approved within 90 days.
However, if a medicinal product is supposed to cause
Decentralized Procedure potential serious risk to public health, CMS(s) will inform
In order to obtain marketing authorizations in several to other CMS, RMS and applicant and further decision in
member states, the centralised procedure is not mandatory; this regard is taken within 30 days. Within 60 days of the
in such case the decentralized procedure is to be used. An communication of the points of disagreement, all member
application is submitted to competent authorities of each of states reach to an agreement on the action to be taken [13,14].
the member states, where a marketing authorization is to be After reaching to an agreement of the member states, the
sought. The information like quality, efficacy, safety, RMS records the agreement and informs to the applicant.
administrative information shall be submitted and a list of However, if the member states could not reach an
all Concerned Member States (CMSs) and one member agreement, then CHMP intervenes and take a final decision
state to act as Reference Member State (RMS). A draft keeping in view of the written or oral explanations of the
assessment report on the medicinal product is prepared and applicant. FIGURE 4 represent the decentralized
the CMSs and the RMS validate the application within a procedure for marketing authorization in EU.
time frame of 14 days. The RMS prepare draft summary of
70 days
RMS and CMS validates the application
35 days
90 days or less
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DRUG APPROVAL PROCESS INDIA and requirements for clinical trials, which was further
The Drug and Cosmetic Act 1940 and Rules 1945 were revised in 2005 to bring it at par with internationally
passed by the India's parliament to regulate the import, accepted procedure [16].
manufacture, distribution and sale of drugs and cosmetics. When a company in India wants to manufacture/ import a
The Central Drugs Standard Control Organization new drug it has to apply to seek permission from the
(CDSCO), and the office of its leader, the Drugs Controller licensing authority (DCGI) by filing in Form 44 also
General (India) [DCGI] was established. In 1988, the submitting the data as given in Schedule Y of Drugs and
Indian government added Schedule Y to the Drug and Cosmetics Act 1940 and Rules 1945. In order to prove its
Cosmetics Rules 1945. Schedule Y provides the guidelines efficacy and safety in Indian population it has to conduct
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clinical trials in accordance with the guidelines specified in 10-12 patients at each dose level. The confirmatory trials
Schedule Y and submit the report of such clinical trials in (Phase III) are conducted to generate data regarding the
specified format. efficacy and safety of the drug in ~ 100 patients (in 3-4
Rule- 122A of the Drug and Cosmetics Act says that the centers) to confirm efficacy and safety claims. Phase III
clinical trials may be waived in the case of new drugs trials should be conducted on a minimum of 500 patients
which are approved and being used for several years in spread across 10-15 centres, If the new drug substance is
other countries. not marketed in any other country.
Section 2.4 (a) of Schedule Y of Drugs and Cosmetics Act The new drug registration (using form # 44 along with full
1940 and Rules 1945 says for those drug substances which pre-clinical and clinical testing information) is applied after
are discovered in India all phases of clinical trials are the completion of clinical trials. The comprehensive
required. information on the marketing status of the drug in other
countries is also required other than the information on
Section 2.4 (b) of Schedule Y of Drugs and Cosmetics Act safety and efficacy. The information regarding the
1940 and Rules 1945 says that for those drug substances prescription, samples and testing protocols, product
which are discovered in countries other than India; the monograph, labels, and cartons must also be submitted.
applicant should submit the data available from other
countries and the licensing authority may require him to The application can be reviewed in a range of about 12-18
repeat all the studies or permit him to proceed from Phase months. Figure 5 represents the new drug approval process
III clinical trials [17]. of India. After the NDA approval, when a company is
allowed to distribute and market the product, it is
Demonstration of safety and efficacy of the drug product considered to be in Phase IV trials, in which new uses or
for use in humans is essential before the drug product can new populations, long-term effects, etc. are explored.
be approved for import or manufacturing of new drug by FIGURE 6 describes the drug approval process in INDIA.
the applicant by Central Drugs Standard Control
Organization (CDSCO). The regulations under Drugs and Through the International Conference on Harmonization
Cosmetics Act 1940 and its rules 1945, 122A, 122B and (ICH) process, the Common Technical Document (CTD)
122D and further Appendix I, IA and VI of Schedule Y, guidance has been developed for Japan, European Union,
describe the information required for approval of an and United States.
application to import or manufacture of new drug for
marketing [18]. Most countries have adopted the CTD format. Hence,
CDSCO has also decided to adopt CTD format for
The changes in the Drugs And Cosmetics Act includes, technical requirements for registration of pharmaceutical
establishing definitions for Phase I-IV trials and clear products for human use.
responsibilities for investigators and sponsors. The clinical
trials were further divided into two categories in 2006. In Stages of approval [20,21,22]:
one category (category A) clinical trials can be conducted 1. Submission of Clinical Trial application for evaluating
in other markets with competent and mature regulatory safety and efficacy.
systems whereas the remaining ones fall in to another 2. Requirements for permission of new drugs approval.
category (category B) Other than A. Clinical trials of 3. Post approval changes in biological products: quality,
category A (approved in the U.S., Britain, Switzerland, safety and efficacy documents.
Australia, Canada, Germany, South Africa, Japan and 4. Preparation of the quality information for drug
European Union) are eligible for fast tracking in India, and submission for new drug approval.
are likely to be approved within eight weeks. The clinical
trials of category B are under more scrutiny, and approve The drug approval process varies from one country to
within 16 to 18 weeks [19]. another. In some countries, only a single body regulates the
drugs and responsible for all regulatory task such as
An application to conduct clinical trials in India should be approval of new drugs, providing license for manufacturing
submitted along with the data of chemistry, manufacturing, and inspection of manufacturing plants e.g. in USA, FDA
control and animal studies to DCGI. The date regarding the performs all the functions. However in some counties all
trial protocol, investigator's brochures, and informed tasks are not performed by a single regulatory authority,
consent documents should also be attached. A copy of the such as in India, this responsibility is divided on
application must be submitted to the ethical committee and Centralised and State authorities. Some counties have two
the clinical trials are conducted only after approval of review processes as normal review process and accelerated
DCGI and ethical committee. review process as in USA, China etc. and some countries
have only a single review process as in India. Similarly, the
To determine the maximum tolerated dose in humans, format used for the presentation of dossier submitted for
adverse reactions, etc. on healthy human volunteers, Phase approval of drug is also different. In some countries like as
I clinical trials are conducted. The therapeutic uses and in USA, EU, and Japan , it is mandatory that the dossier
effective dose ranges are determined in Phase II trials in
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APPLICANT
Recommendation to DCGI
Within 12 weeks
If not complete
Review by DCGI
If complete
Refused to grant license
LICENCE IS GRANTED
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