INDIAN DRUG REGULATION:

SCHEDULE Y
Schedule Y
Requirements and Guidelines for
permission to import / manufacture of new
drug for sale or Clinical Trial

Responsibilities
Applications
Appendices
Refinements
Drug Regulatory Laws
1940 - Drugs and Cosmetic act
1985 - Narcotic drugs and psychotropic
substances act
2000 - Ethical guidelines for biomedical
research on human subjects, ICMR
2001 - Indian GCP guidelines
2002 - Amendment to D & C act
2005 - Revised schedule Y
Future :
 Guidelines for pre-clinical data for r- DNA
vaccines, diagnostics & biologicals, DBT.
 Draft guidelines for 5 tem cell research/ regulation,
ICMR.
 Schedule Y 2005
Revised Old

1. Application for permission 1.1 Nature of trials

2. Clinical trial 1. Clinical trials
(1) Approval for clinical trial 1.2 Permission for trials
(2) Responsibilities of Sponsor 1.3 Responsibilities of
(3) Responsibilities of the Investigator(s) Sponsor/Investigator
(4) Informed Consent – New
(5) Responsibilities of ECs - New
(6) Human Pharmacology (Phase I) 5. Human clinical pharmacology (Phase
I)
(7) Therapeutic exploratory trials (Phase 6. Exploratory trials (Phase II)
II)
(8) Therapeutic confirmatory trials (Phase 7. Confirmatory trials (Phase II)
II)
(9) Post Marketing Trials (Phase IV) – New
3. Studies in special populations 8. Special studies
(1) Geriatrics
(2) Pediatrics
(3) Pregnant or nursing women
4. Post Marketing Surveillance 12. Post-marketing surveillance study
5. Special studies: BA/BE Studies – New
Schedule Y 2005
Revised Old
Data to be submitted along with the application Data required to be submitted with application to
to conduct clinical trials/import/manufacture of for permission to market a new drug
new drugs for marketing in the country

2.1 Information on active ingredients 2.3 Specifications of active and inactive

ingredients
2.2 Physicochemical Data 2.1 Physicochemical proportion
2.3 Analytical data – New
2.4 Monograph specification 2.4 Tests for identification of the active
ingredient and method of its assay
2.5 Validations – new
2.7 Data on Formulation 2.2 and 2.5
3.4 Safety Pharmacology – New
4.3 Male Fertility Studies – New
4.6 Allergenicity/Hypersensitivity – New
11. Samples and Testing Protocols 10.3 Sample…with testing protocol
 Regulatory Authorities
MINISTRY OF HEALTH

Health Secretary M/O Chemistry & Fertilizer NPPA

DBT
DGHS M/O Science & Technology
GEAC

ADD.
DCGI M/O Environment SECRETARY

State Drug Regulatory Authority

CDTL
FDA
Investigational New Drug (IND)

New chemical entity or product

having therapeutic indication but
never tested on human beings
Importan t conc erns
SAE / SADR
Event associated with death, hospitalization
disability, congenital anomaly or otherwise
life- threatening.
Adverse Event (AE)
Untoward medical (I/S/D) occurrence that
does NOT necessarily have relationship with
the treatment.
ADVERSE DRUG REACTION

Noxious / unintended response at

therapeutic doses for
approved product,
or any dose for unapproved
product,
and
a possible Adverse Event
 Drugs and Cosmetics
Act 1945
Rule Permission for
2 A – Import
B – Manufacture [except drugs under
schedule C and C(1)]
D – Fixed dose combination
DA – Clinical trial
DAA – CT definition
E – New drug definition
122 – DAA
Clinical Trial Definition
Systematic study of new drugs in human
subjects;
To generate data for discovering/verifying
clinical,
pharmacological (PK & PD) or adverse effects;
&
To determine safety and efficacy of the new
drug
 122 – E
New drug definition
Not used in the country
Approved drug : 1. New claims
(Indications,dosage,
dosage form, route)
2. FDCs
(New / Modified)
Note : Vaccines are new drugs unless
1. Certified
2. Till 4 year or
3. Included in IP
SPONSOR’S RESPONSIBILITIES
Quality Assurance : Adopt GCP Guidelines

Trial Status Report to Licensing Authority : Annually

Premature Termination : Summary report within 3

m ( Study, Pt. no., Dose, Duration, ADR &
reasons for discontinuation )

Serious Adverse Event : Report to LA & other

investigators within 14 days
INVESTIGATOR’S RESPONSIBILITIES

Adhere to approved Protocol & GCP

Guidelines
Document SOPs
Management of all ADR / AE
Reporting unexpected AE to :
- Sponsor within 24 hours
- EC within 7 days
EC RESPONSIBILITIES
Safeguard rights, safety & well being
Protect vulnerable subjects
Obtain and maintain record of SOPs
Ongoing review based on Periodic progress
report
If EC revokes its approval
- Record reasons for it
- Inform the Investigator & LA immediately
 ESSENTIAL STEPS OF CLINICAL PHARMACOLOGY
Phase I (Human Pharmacology)
Safety & Tolerability ( PK, PD & MTD

Phase II (Th. Exploratory Trial)

Therapeutic benefits in few patients

Phase III (Th. Confirmatory Trial)

Therapeutic benefit in more patients

Phase IV (Post Marketing Trials)

Related to Approved indication
 REGULATORY REQUIREMENTS FOR
CLINICAL PHARMACOLOGY
Drug discovered in India : Phase I data

Drug discovered outside India : Foreign Phase I data

required for Phase II/III permission

Accompanying documents : Protocol, CRF,

IB, IC, EC Clearance,
Investigator’s undertaking

Sample size : Depending upon type of study

 REGULATORY REQUIREMENTS FOR
CLINICAL PHARMACOLOGY

EC application can parallel DCGI application

Toxicological / clinical data abbreviate, deferred

or omitted for life threatening diseases
(or diseases of special relevance to Indian health
Scenario)

Amendments notified to DCGI & EC within 30

days & approval obtained
BA / BE INFORMATION
Drugs approved elsewhere require BE
studies with the reference formulation
Effect of Food
Dissolution and BA data
Compliance with ICMR guidelines for
BA / BE Studies
 PROCESS
APPROVAL FORM
APPLICATION 45 (IMP FF)
FORM 44
-Imp ff
APPROVAL FORM
-Imp rm
45 A (IMP RM)
-Mfg ff
-Mfg rm
-CT APPROVAL FORM
46 (MFG FF)

APPLICATION FORM
46 A (MFG RM)
NOC FOR CT + Test
License for Import
 Application Fees
Import ff/ Mfg ff/ Import bulk + Mfg ff = Rs 50,000/-
of new drug
Application by same applicant, = Rs 15,000/-
for modified dosage form or with new claim
Secondary applicants after 1 = Rs 15,000/-
year of approval
Import / Mfg FDC = Rs 15,000/-
Conduct Clinical trial with ND/IND
Phase I = Rs 50,000/-
Phase II = Rs 25,000/-
Phase III = Rs 25,000/-

No separate fee to be paid along with application for import / mfg based on
successful completion
TEST LICENCE
Application form No. 12
Material Justification Plan
Treasury Challan ( Rs. 100 )

Test License obtained in form 11

PERIODIC SAFETY UPTAKE REPORTS ( PSUR)

Report all relevant new information following

patient exposure

Summarize the market authorization status in

different countries and any significant variations
related to safety

Suggest changes in Product Information

PSUR TIME FRAME ( within 30 days )
First 2 years – Half yearly
Next 2 years – Annually

Drafts of Labels & Cartons

Comply with Rules 96 of D & C rules , 1945
No changes in Package insert once approved
Appendices
I : Data required for import/manufacture/

conduct CT of new drugs

I A : …. Drugs approved in other country
II : Format for clinical study reports(ICH E6)
III : Animal toxicology
IV : Animal pharmacology
V : Informed consent
Appendices
VI : FDC
VII : Undertaking by the investigator
VIII : Ethics committee
IX : Stability testing
X : Proposed protocol
XI : SAE Reporting
Loopholes in Schedule Y

New drug remains new for 4 years. Thus, Phase IV

trials require permission. However, Approved drug
and indication need not require permission.

Approval of Amendment could be a problem.

SOPs for investigators and documentation of tasks –

Template required.

Unmet medical needs to be added to CT waiver.

Loopholes in schedule Y

EC chairman outside institute is a rarity.

Exhaustive species data (App.I-A)and comparative

evaluation (App. I) not helpful for differentiation.

All CT supplies to be included in Form 11.

Requirement to support data protection

 Unattended Areas
Regulations for :
1. Biologics : vaccines
Blood products
Tissue
Cellular/gene therapy
6. Herbals
7. Medical devices
8. Pharmacovigilance
9. Electronic records