This document provides an overview of pharmaceutical regulations for drug approval in the US, EU, and India. It discusses the drug approval processes and requirements in each region, including the types of applications submitted (e.g. ANDA, NDA), necessary documentation, evaluation timelines, and guidelines followed (e.g. ICH). It also compares some key parameters of the regulatory frameworks like bioequivalence study designs, criteria, and pharmacokinetic measures assessed between the different jurisdictions.

1. Pharmaceutical regulations for drug
approval in USA, EU & India
SWETA YADAV
M PHARM
EXECUTIVE –CLINICAL RESEARCH

2. Contents
 Introduction
 Drug approval in USA
 Drug approval in Europe
 Drug product approval process in India
 Comparative study of regulatory guidance in different countries

3. A Historical perspective of drug regulation
and approval
 During the 20th century, there were no law’s & regulations to protect the public
from the unfavorable effects of the drugs.
 Misfortune, disaster, and tragedy had triggered most of the advances in drug
regulation.
 Thalidomide tragedy (1962)
 JAKE-LEG paralysis (1930)
 Elixer Sulfinamide (1937)

4. Pharmaceutical markets
1. Regulated: USA, EU, Japan (follows ICH paten. i.e. CTD)
2. Semi-Regulated: India, ASEAN countries, Russia, China, Brazil. (country specific
product registration guidelines are followed)
3. Non-Regulated: African countries. (min document is required for drug approval
process)

5. Drug approval in USA

6. Different types of Drug applications that can be submitted to
FDA
IND
 Application filed to FDA in order to start clinical trials in humans on the basis of data obtained from the preclinical trials.
 Sponsor is responsible for submitting the IND Application.
NDA (505 b2)
 If clinical studies confirm that a new drug is relatively safe and effective and will not pose unreasonable risks to patients, the
manufacturer files a NDA.
 This is the actual request to manufacture and sell the drug in the US.
ANDA (505 j)
 It’s an application mode for generic drugs.
 Sponsor is not required to generate or produce clinical studies that were done for the original brand name product.
 Instead, must prove that the generic product is same & bioequivalent to the brand name product.
Biologic Licence Application (BLA)
 Biologic products are approved for marketing under the provision of the Public Health service Act.

10. NDA document should explain
information on
 CT
 Preclinical studies
 Ingredients of New drug
 Manufacturing process
 Labelling
 Packaging
 How the drug behaves in body

11. Multiple copies OF NDA
ARCHIVED COPY – It contains all sections of the NDA including cover letter, form FDA-356 h
(application to market a new drug for human use ) administrative section , NDA index and all
technical sections .
It is the only copy that contains the case report tabulation and case report form.
REVIEW COPY – It contains a NDA technical section along with the cover letter , form FDA-356 h ,
NDA index as well as individual table of content , the labelling section and application summary
FILED COPY – This is required by the FDA inspector during pre-approval facilities inspections.
In addition to the content review copy it includes the CMC and method validation package.

13. Types of ANDA / 505 (j) Filling
While filling an ANDA , the generic company has to choose one of the following four options
 Para I –The drug has not been patented . patent information is not available in orange book .
 Para II –The patent for the drug has already expired .
 Para III –The patent for product exists but the generic company wants to enter the market after the date of
patents expiry passes .
 Para IV -Patent is not infringed upon or is invalid .
Para IV filling are most lucrative , tedious , time consuming and expensive of the para I ,para II and Para III.
on successful outcome the generic applicant enjoy the six months exclusivity in the market.

14. Drug approval in EUROPE

15. Europe submission
Types of Procedure
 A centralized
 A decentralized
 Mutual recognition
 National authorisation procedure

16. Centralized procedure
 Marketing authorization is valid throughout the EU.
 Each member state approval is not required.
 Timeline: 210
 Compulsory for:
 Medicines which are derived from any biotechnology processes.
 Anti-cancer drugs, HIV/AIDS, diabetes, neurodegenerative disorder or autoimmune
diseases.
 Orphan medicines.

18. Decentralized Procedure
 RMS-first member state
 CMS- other member states
 Simultaneous application in more than one EU country
 Time: 210 days.

20. Mutual recognition procedure (MRP)
 Applicant submits identical dossier to all EU member states.
 RMS decides to evaluate the medicinal products, issues a report to other states on
its own findings.
 Generic industry is the major user of this type of drug approval procedure.
 Time: 390 days.

22. EU Directive on pharmaceutical
submission
Article 10
 Generic drug can be placed in the market only if authorisation of Reference drug had
elapsed a duration of 10yr.
 Extension period of 1 yr is granted, if more than 1 indication is found i.e is clinically
significant.
 Reference drug: Authorized under Article 6 & is in accordance with provisions of
Article 8.
 Generic drug: API is same that of Reference product except the pharmaceutical
excipients.
 Article 10a: BABE application, Bibliographic application.
 Article 10b: New Combination drugs, submitted in accordance with Article B3(i).
 Article 17: MAA can be submitted in more than two member state accordance to
article 27-39.

23. Drug approval in India

24. Drug regulation system in India
 The Drug & Cosmetics Act 1940 & Rules 1945
 CDSCO & DCGI was established
 Schedule Y (1988,2005): Provides guidelines & requirements for conduct of Clinical trials.
 Clinical trial was further divided into two in 2006,
 Drug regulatory authority ensures: Quality, Safety & Efficacy
 Form 44: To Mfr/import a new drug, along with the data mentioned in Schedule Y (data of
chemistry, mfg, animal studies, date in regard to protocol, IB, ICD)
 FORM CT-16: Application for grant of license to import new drug or investigational new drug for
clinical trial or bioavailability or bioequivalence study or for examination, test and analysis
 FORM 29: License to manufacture drugs for purpose of examination, test or analysis

25. Functions of………..
DCGI:
Matters related to product approval and standards, clinical trials, introduction of new drug, and
licenses of new drugs are handled by the DCGI.
CDSCO:
 Approval of new drugs and clinical trials
 Import registration and licensing
 Licensing of Blood Banks & Medical Devices
 Amendment to D&C Act and Rules
 Banning of drugs and cosmetics
 Grant of TL, NOC’s for Export
 Testing of Drugs

27. Comparative study of regulatory guidance in different
countries
Sl No. Parameter USA Europe India
1. Application ANDA MAA MAA
2. Debarment certification Required NA NA
3. Approval timeline 18 months 12months 12months
4. Presentation eCTD/Paper eCTD eCTD
5. Finished pdt justification ICHQ6A ICHQ6A ICHQ6A
6. Stability data required at the
time of submission
1 Batch 2 Batch -
7. Bioequivalence study
followed
USA Guideline It also
accepts other country
guidelines
E.U. Guidelines It also
accepts
other country guidelines
-

28. Sl No. Parameters US EUROPE CANADA
1. Study design Non-replicated, randomized, crossover
studies
Non-replicated, randomized, crossover
studies
Non-replicated, randomized,
crossover
studies
2. Fasting/fed state studies Fasting and fed Fasting Fasting
3. Volunteers Sufficient to achieve adequate power >12 (Min 80% power of acceptance
criteria)
Min 80% power of acceptance
4. Study dose
Test
Reference
Made by the manufacturer
Reference listed drug in USA
Made by the manufacturer
European reference product
Made by the manufacturer
Canadian reference product
5. Sampling points 12–18 samples, more samples should
be collected at Tmax, to be continued
upto 3 or more half lives
At least 2 samples before expected
Tmax, 3–4 terminal log–linear phase
12–18 samples per subject/dose

29. Sl No. Parameter USA Europe Canada
6. Analytical method validation
parameters
Accuracy, precision, selectivity,
sensitivity,
reproducibility, calibration curve,
and stability
Accuracy, precision, repeatability,
intermediate precision specificity,
detection. limit of quantitation,
linearity range
Stability, L.O.Q, specificity,
recovery,
standard curves, precision and
accuracy
7. Moieties to be measured in
plasma
Active drug/metabolites if applicable Active drug/metabolites if Active drug/metabolites if
applicable
8. Pharmacokinetic parameters Cmax, Tmax, AUC0–t and AUC0–1,
t1/2, kz
Cmax, Tmax, AUC0–t and AUC0–1,
t1/2, kz
Cmax, Tmax, AUC0–t and AUC0–1,
t1/2, kz
9. Criteria for bioequivalence 90% CI
80.00–125.00% for Cmax, AUCt,
AUC0–1
90% CI
80.00–125.00 for Cmax, AUCt,
AUC0–1 (for highly variable drugs
75–133%)
90% CI 80–125% for Cmax, AUCt,
AUC0–1
10. GCP requirements ICH GCP guidelines ICH GCP guidelines ICH GCP guidelines