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CDSCO
Biological Division Presentation By:
S.P. Shani
Deputy Drugs Controller
(I)
Introduction:
• Drugs fall under the Concurrent list
of the Constitution
• Drugs regulated under the
• Drugs and Cosmetics Act 1940
• Drugs and Cosmetics Rules 1945
• The Act is a Federal Act, enforced by
both Federal and State Govts.
Implementing Authorities
Federal Govt: Ministry of Health & Family Welfare
• Directorate General of Health Services
• Central Drugs Standard Control Organization
(CDSCO)
State Govts: State Drug Licensing Authorities, under Department of
Health of respective State Govts.
Objective: To ensure availability of safe, efficacious and
quality Drugs, Cosmetics and Medical Devices
Preamble:
To regulate Manufacture, Sale, Distribution and
Import of
• Drugs
• Cosmetics
• Biologicals
• Medical Devices
• Veterinary Drugs
CDSCO:
• The Central Drugs Standard Control
Organization (CDSCO) is headed by the
Drugs Controller General (India).
• It is the Central Authority for discharging
functions assigned to the Central
Government under the Drugs and Cosmetics
Act, 1940 and Rules, 1945.
Functions
CDSCO
Approval of new drugs and clinical trials
Import Registration and Licensing
Licensing of Blood Banks, LVPs, Vaccines, r-DNA
products & some Medical Devices
Amendment to D &C Act and Rules
Banning of drugs and cosmetics
Grant of Test License, Personal License, NOCs for Export
Testing of Drugs
Functions
State Licensing Authorities
Licensing of Manufacturing Site for Drugs including API and
Finished Formulation
Licensing of Establishment for sale or distribution of Drugs
Approval of Drug Testing Laboratories
Monitoring of Quality of Drugs and Cosmetics marketed in the
country
Investigation and prosecution in respect of contravention of
legal provision
Recall of sub-standard drugs
•Mumbai
New Delhi
Chennai
North Zone (Ghaziabad)
Kolkata
.
West Zone (Mumbai)
South Zone (Chennai)
East Zone (Kolkata)
CDSCO, HQ
CDSCO – Geographical Location Zonal /Sub ZonalOffices
•Hyderabad
Ahmedabad
Port Offices/Airports : 13
Laboratories : 6
28 States
7 Union Territories
Zone (Ahmedabad)
Zone (Hyderabad)
•Proposed Zonal/Sub Zonal Offices (2) :
•Guwahati, Indore,
Sub Zone (Bangaluru)
Bangaluru
Ghaziabad
Sub Zone (Chandigarh)
Chandigarh
Jammu
Sub Zone (Jammu) and (Goa) Goa
Drug Testing Laboratories
Central Laboratories: 6 (including CDL Kolkata)
State Labs: 26
Vaccines: CDL, Kasauli (NCL)
r-DNA and Diagnostic kits: NIB, Noida
Drugs Controller General (I)
HEAD QUARTER SUB ZONAL
OFFICE (4) ZONAL
OFFICE (6)
LABORATORY
(6) PORT OFFICE
(13)
• New Drugs
• Clinical Trials
• Imports
• Biological
• Medical
Devices
•Export
•QC
• Pharmco.Vig
•Legal etc
• GMP Audits
• Enforcement
• Draw drug
Samples
•GMP Audits
•Coordination
with States
•Import
•Export
• Testing of
Drugs
•Validation of
Test protocols
Central Drugs Standard Control Organization
BIOLOGICAL DIVISION
BIOLOGICAL DIVISION
DDC(I) (Technical Head)
(Mr. S.P Shani)
ADC(I) (Mrs.Swati Srivastava)
Vet
erin
ary
va
ccin
e
DI
(An
ku
r)
PS
UR
, A
EF
I, P
MS
,
coo
rdin
ati
on
wit
h
imm
un
iza
tio
n D
ivis
ion
, &
com
pla
int
ha
nd
lin
gD
I (
Rav
ind
ra)
Cli
nic
al T
ria
l In
spec
tio
n
DI
(Sh
rad
dh
a) &
DI
(An
ku
r)
Ap
pro
va
l o
f V
acc
ine
(MA
+C
T)
Vir
al
DI
(Yo
ges
h)
Fo
rm 2
8D
DI
(Raj
esh
), &
DI
(Min
aksh
i)
Fo
rm-2
9, T
est
Lic
ense
an
d
Ex
po
rt N
OC
DI
(Raj
esh
)
Po
st A
pp
rov
al
Ch
an
ges
DI
(Vin
od
) &
DI
(Ch
and
rash
ekar
)
Ap
pro
va
l o
f V
acc
ine
(MA
+C
T)
Ba
cter
ial
DI
(Raj
esh)
Drugs Controller General (India)
(Dr. G. N. Singh)
Ru
le 3
7,
Imp
ort
Reg
istr
ati
on
DI
(Sh
ash
ip
aul)
&
DI
(Man
ish
)
DDC(I) (QA Head)
(Dr. K. Bangarurajan)
ADC (I)
(Rubina Bose)
Zones / Sub zonesHeads
Zon
es / S
ub
zon
es
GM
P I
nsp
ecto
rate
Technical Data Associate (1 Nos.)Technical Data Associates (11 Nos)
DDC(I) (AEFI Head)
(Mrs. Annam Vishala)
ADC(I) (Somnath Basu)
ADC(I) (Dr. I.S. Hura)
ORGANOGRAM OF BIOLOGICAL DIVISION
(Dr. G.N. Singh)
Drugs Controller General (I)
Drugs Inspectors:
1. V. Rajappan
2. S. John Gerard
3. P. Dhinesh Pandian
4. Arvind Hiwale
5. Nisha Sankhwar
6. Manish Singhal
7. Saurabh Garg
8. Amol Kandekar
9. Sourabh Mittal
10. Rakesh Negi
11. Devendra Nath
Date:
ADC(I) (Jayant G.Khedkar)
Ap
pro
va
l o
f r-
DN
A
pro
du
cts
(MA
+C
T)
DI
(Sh
rad
dh
a) &
DI
(Ch
and
rash
ekar
)
Ste
m C
ells
DI
(Sh
rad
dh
a)
Activities undertaken in Biological Division
1. New Drug Approvals – Biologicals.
2. Post Approval Changes
3. Registration and Import permission of
Biologicals.
4. Licensing Activity - Form 28 D and Form 28
E (Blood Products).
5. Issuance of Test License.
Types of Biological Products 1. Recombinant DNA Products.
2. Bacterial Vaccine.
3. Viral Vaccine.
4. Combination Vaccine.
5. Veterinary Vaccine.
6. Blood Products.
7. Stem Cells.
8. AEFI Data.
9. Post Approval Changes (Compulsory for
biological products only).
Definition of New Drug
• As per under Rule 122-E New Drug is defined “A drug, including bulk drug substance which has not been used in the country to any significant extent under the conditions prescribed, recommended or suggested in the labeling thereof and has not been recognized as effective and safe by the licensing authority mentioned under Rule 21 for the proposed claims.
• A drug already approved by the Licensing Authority mentioned in Rule 21 for certain claims , which is now proposed to be marketed with modified or new claims , namely , indications, dosage, dosage form ( including sustained release dosage form) and route of administration.
All vaccines and r-DNA products are New Drugs
vide G.S.R. 45 (E) dated 24/01/2011.
122-A clearance required for imported
vaccines/r-DNA products.
122-B clearance required for Indigenously
manufactured vaccine/r-DNA products.
Regulatory Requirement for Market Authorization of Biological
Products
• Drugs and Cosmetics Act & Rules,
1945.
• Guidance for Industry
• Specific for Biological Products
Regulatory Requirement for Market Authorization of Biological
Products
Legal Provisions for regulation of Clinical Trials
Requirements and Guidelines - Schedule Y
Rule 122 DA
Rule 122 DAA
Definition of New Drugs
Rule 122 DB
Rule 122 E
Definition of Clinical trials
Suspension / Cancellation of permissions
Permission to conduct clinical trial
Technical Review and
Forward the file to
Concern DI’s
for validation
Manufacturers
for submission
Submission of application
in CRU After acceptance
By Pre screening officers
And FTS No. generated
Flow of Applications in Biological Division: flow chart in India
Pre-screening 1. Check administrative
2. Check legal document
3. Check fees
1st Level
Review
Central Registry
Unit
DDC (I)
ADC (I)
DI’s
TDA’s
DCG(I)
File signed and
send back to
concerned officer for
issue the letter
Letter send to
CRU for issue 2nd Level
Review
On Site Evaluation
CMC Evaluation
NDAC
Zonal
Hard and Soft
copies
IND
CDL, Kasauli
for Vaccines
State Licensing
Authority (SLA) – License
for Counter Signature
License to Manufacture Vaccine (Form 28D): Flow chart in India
1. Check administrative (Grant/
Fresh/ Additional Product/
Dosage Form)
2. Inspection Report
3. Check New Drug Permission
DDC (I)
ADC (I)
DI’s
TDA’s
Query Letter
CRU
FTS no. allotted
through CRU DCG (I)
CRU for Dispatch
Approval
Guidance for
Industry (Specific for
Biological Products) published on
CDSCO website : www.cdsco.nic.in
on 4th Dec, 2008
• Submission of Clinical Trial
Application for Evaluating Safety
and Efficacy
• Requirements for permission of
New Drugs Approval
• Post approval changes in
biological products:
Quality safety and Efficacy
Documents • Preparation of the Quality
Information for Drug Submission
for New Drug Approval:
Biotechnological/Biological
Products
Regulation for r-DNA Technology based
Therapeutic proteins - Indian Scenario
The Guidelines on Similar Biologics was prepared by CDSCO and DBT laid down the regulatory pathway for similar biologic claiming to be similar to an already authorized reference biologic.
CDSCO is the national regulatory authority in India that evaluates safety, efficacy and quality of drugs in the country.
DBT through Review Committee on Genetic Manipulation/ Institutional Biosafety Committee is responsible for overseeing the development and preclinical evaluation of recombinant biologics.
There are three Competent Authorities involved in
approval process namely :
a) Review Committee on Genetic Manipulation
(RCGM)/IBSC under Department of Biotechnology
(DBT), Ministry of Science and Technology.
b) Genetic Engineering Appraisal Committee (GEAC)
under the Ministry of Environment and Forests
(MoEF) and
c) Central Drugs Standard Control Organization
(CDSCO) under Ministry of Health & Family
Welfare
Competent Authorities
Filing of Information as per CTD
Module I: Administration/Legal Information Module II: Overall Summaries Module III: Quality Information (Chemical, Pharmaceutical and Biological) Module IV: Non-Clinical Information Module V: Clinical Information
For Biological section Comprehensive Information is asked as per
CTD Module:-
MODULE - 1
CTD Format
Module
CTD Format
Section Headings
1
1.1 Comprehensive table of contents (Modules 1 to 5)
1.2 Administrative information
1.2.1 Application in Form 44 and Treasury Challan (fee)
1.2.2 Legal and statutory documents
1.2.2.2 Legal documents pertaining to application (to be notarized):
a) A copy of plant registration / approval certificate issued by
the Ministry of Health / National Regulatory Authority of the
country of origin.
b) A copy of approval, if any, showing the drug is permitted for manufacturing
and/or marketing in the country of origin.
c) A copy of Pharmaceutical Product Certificate (PPC) as per
WHO GMP certification scheme for imported drug products
d) A copy of Free Sale Certificate (FSC) from the country of
origin for imported drug products
e) Certificate of Good Manufacturing Practices of other manufacturers
f) Batch release certificate issued by NRA for imported
products.
MODULE - 1
CTD Format
Module
CTD Format
Section Headings
1.2.2.3 A copy of Site Master File
1.2.2.4 Certificate of Analysis from Central Drug Laboratory (India) of three
consecutive batches.
1.2.2.5 Product Permission Document (PPD)
1.2.3 Coordinates related to the application
1.2.4 General information on drug product in including Summary of product
characteristics, Product Labeling etc
1.2.5 Summary protocol of batch production and control
1.2.6 List of countries where MA or import permission for the said drug
product is pending and the date of pendency.
1.2.7 List of countries where the drug product has been licensed and
summary of approval conditions.
1.2.8 List of countries where the drug product is patented.
1.2.9 Domestic price of the drug followed in the countries of origin in INR.
1.2.10 A A brief profile of the manufacturer’s research activity
1.2.11 A brief profile of the manufacturer’s business activity in domestic as
well as global market.
1.2.12 Information about the expert(s)/ Information regarding involvement of
experts, if any
1.2.13 Environmental risk assessment
MODULE - 2
Introduction
Quality overall summary
Overview of non-clinical studies
Non-clinical Summary
Overview of clinical studies
Clinical summary
MODULE - 3
Quality Information (Chemical, Pharmaceutical and
Biological)
Strain details
Name and source (if any)
In case of products derived from r-DNA technology,
the following details shall also be furnished
Clone development (for recombinant products)
• Details on source Nucleic acid
Nucleic acid sequence
MODULE – 3
• Vector(s)
Details about vector, please enclose the map of the
vector gene
• Host(s) that carrying the vector(s)/ target gene(s)
Substrate details (For cell culture based products)
Details of name and source of substrate
Master seed and Working seed details
MODULE – 3
Drug substance(s): Information must be submitted
for each drug substance in the product.
General information, starting materials and raw
materials
Manufacturing process for drug substance
Characterization of drug substance
Quality control of drug substance
Reference standards
Container closure system
Stability of drug substance
Drug product
Description and composition of drug product
Pharmaceutical development
Manufacture of drug product
Control of excipients (adjuvant, preservative, stabilizers and
others)
Control of drug product
Reference standards of materials
Container closure system
stability of drug product
Appendix
Details of equipment and facilities for production of drug
product: master formula, batch record and set release
documentation in respect of consistency batches
Safety evaluation of adventitious agents
MODULE – 3
MODULE - 4
Non-Clinical Reports
Reports on studies
Pharmacology
Pharmacokinetics
Toxicology
• General toxicology
• Special toxicology (Studies of genotoxicity and carcinogenicity)
• Toxicity of new substances used in formulation (new adjuvant,
stabilizers, additives)
Appendix III
Animal Toxicity
Non Clinical Toxicity studies
Appendix – III of Schedule Y {Animal Toxicity (Non Clinical
Toxicity studies)}
• Systemic Toxicity studies
Single and repeated dose toxicity studies
• Male fertility study
• Female reproduction and developmental toxicity studies
Female fertility study
Treratogenicity study
Preinatal study
• Local Toxicity
• Allergenicity / Hyper sensitivity
• Genotoxicity
• Carcinogenicity
MODULE - 4
Animal Pharmacology
• Specific Pharmacological action
• General Pharmacological Action
• Follow-up and supplemental safety Pharmacology study
• Timing of safety Pharmacology studies in relation to clinical
development
Prior to First administration in humans
During clinical development
Before applying the marketing approval
MODULE - 4
MODULE - 5
Clinical Reports
Reports of clinical studies
• Phase I studies
• Phase II studies
• Phase III studies
Bridging Studies
Phase IV studies and / or Pharmacovigilance Plan if required
Non-inferiority studies (for combined vaccines, or approved
vaccines prepared by new manufacturers)
Case Report Forms and Individual Patient Listings
Appendices of Schedule Y
Appendix V of Schedule Y - Informed Consent
Appendix VII of Schedule Y - Undertaking by the Investigator
Appendix VIII of Schedule Y - Ethics Committee
Ethics Committee should be registered as per Rule 122 DD of
Drugs & Cosmetics Rules 1945 under GSR No. 75 (E) dated 08th
Feb, 2013
Appendix IX of Schedule Y - Stability Testing of the New Drug
Appendix X of Schedule Y - Content of proposed protocol for
conducting clinical trials
Appendix XI of schedule Y - Data elements for reporting
Serious Adverse Events occurring in a clinical trial
• Detailed Guidelines for conducting Inspection of clinical trial sites and Sponsor/CRO are already available at CDSCO website (www.cdsco.nic.in) • Covers the inspection of Ethics Committees
Clinical Trials
Thank You