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Import & Registration of drugs in India
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Presentation overview
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All medicines for internal or external use of human or animals and all
substances intended to be used for or in the diagnosis, treatment, mitigation
(decreasing) or prevention of any disease or disorder in human beings oranimals, including preparations applied on human body for the purpose of
repelling insects like mosquitoes; and
Such substances (other than food ) intended to affect the structure or any
function of the human body or intended to be used for the destruction or
vermin or insects which cause disease to human beings or animals.
Allsubstances intended for use as components of a drugincluding empty
geletin capsules; and
Such devices intended for internal or external use in the diagnosis, treatment,
mitigation or prevention of disease or disorder in human beings or animals.
DRUG
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LAWS PERTAINING TO IMPORT, MANUFACTURE AND
SALE OF DRUGS IN INDIA
HISTORICAL PERSPECTIVE
In the beginning of the current century Drug Industry was
practically non-existent in India
Pharmaceuticals were being important from abroad.
The first world war changed the situation and not only were
finished and cheap drugs imported in increasing volume, the
demand for indigenous products also was voiced from all sides.
The Government was, therefore, called upon to take notice of the
situation and consider the matter of introducing legislation to
control the Import, manufacture, distribution and sale of drugs
and medicines.
The Drugs and Cosmetics Act, 1940
The Pharmacy Act, 1948
The Drugs and Magic Remedies (Objectionable Advertisement) Act,
1954
The Narcotic Drugs and Psychotropic Substances Act, 1985
The Medicinal and Toilet Preparations (Excise Duties) Act, 1956
The Drugs (Prices Control) Order 1995 (under the Essential
Commodities Act)
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Drug Regulatory Structure In India
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Drugs Controller General of India ( DCGI ) Dr. Surinder Singh
Main duties : New drug approval, Standards of drugs, drugs import, co-ordination
with State FDAs
State FDAs Maharashtra FDA commissioner
Main duties: Manufacturing, sale and Distribution of drugs
National Pharmaceutical PricingAuthority ( NPPA)Chairman
Main Duties: Drug Pricing
Department of Biotechnology - Secretary
Main Departments related to Pharma
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Regulatory Bodies
Directorate General of Health Services (DGHS)
Ministry of Health & Family WelfareDrug Controller General (India) (DCGI)
Directorate General of Foreign Trade (DGFT)
Indian Council of Medical Research (ICMR)
Department of Biotechnology (DBT)Ministry of Environment & Genetic Engineering
Approval Committee (GEAC)
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Ministry of
Chemicals &
Fertilizers
NPPANational
Pharmaceutical PricingAuthority
Pricing
Regulations
Ministry of
Sci & Tech
DBTDepartment ofBiotechnology
Ministry
of Enviro
AdditionalSecretary
State Drug Regulatory Authority
FDA
Mfg. Lic. for New Drug after approval
GEACGenetic Engineering
Approval CommitteeDCGIDrug ControllerGeneral of India
DGHSDirector General ofHealth Services
Health Secretary
Ministry
of Health
CDL/CDTLGov. Drug Testing
Laboratories
Approval of New Drug
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Regulatory Process for Approval of a New Drug in India
Nature of Product
Life Saving Non - Life Saving
Non- Biotech Non- BiotechBiotech
Clinical trial waiver
NDA
Expert
ReviewCDL
Testing specs.
Clinical trial
IND
CT
permission
CDL
testing
Data presentation
GEAC clearance
CDLwaiver
possible
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122 E NEW DRUG DEFINITION
(a) a new substance of chemical, biological or biotechnological origin; in
bulk or prepared dosage form; used for prevention, diagnosis, or treatment
of disease in man or animal; which, except during local clinical trials, has
not been used in the country to any significant extent; and which, except
during local clinical trials, has not been recognized in the country as
effective and safe for the proposed claim;
(b) 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 forms (including sustained
release dosage form) and route of administration;
(c) a fixed dose combination of two or more drugs, individually
approved earlier for certain claims, which are now proposed to be combined
for the first time in a fixed ratio, or if the ratio of ingredients in an already
marketed combination is proposed to be changed, with certain claims, viz.
indications, dosage form (including sustained release dosage form) and
route of administration. [See items (b) and (c) of Appendix VI to Schedule Y.]
New
DrugWhat isaNew Drug ?
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Importing Country
India
Form 40
Application for Site
Registration 40
Site RegistrationApplication
Form 40
Fees: $ 1500 for site
+ $ 1000 drug at that site
Exporting Country
D I (Plant Master File DI)
D II (Drug Master File DII )
PowerOfAttorney POA
DCGI
Form 41
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Importing Country
India
Form 8
Application for licence to
import drugs
Import licenceApplication
Form 8
Form 9
Fees Rs. 1000 (20$)
Exporting Country
Form 9
Undertaking to
accompany form 8
DCGI
Form 10
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Schedule Y
Regulation and guidelines for permission to
import and / or manufacture of new drugs forsale or to undertake clinical trials
It has outlined extensive study criteria in line
with the globally accepted formats such as ICH
and US FDA guidelines
REFER TO RULES 122A, 122B, 122D, 122DA,
122DAA and 122E
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Part X-A ofD & C Rules, 1945
122-A Application for permission to import new drug
122-B Application for approval to manufacture newdrug
122-D Permission to import or manufacture FDC
122-DA Permission to conduct clinical trials for New
Drug / Investigational New Drug
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Schedule Y Highlights
No clinical trial should be conducted without thewritten permission from licensing authority.
For drugs not approved / marketed in India,permission is granted to initiate study a phaseearlier to the phase of trials in other countries.
Phase I studies of drug discovered in other
countries are usually not allowed.
Trials in children are usually allowed only afterPhase III in adult is completed.
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Schedule Y Highlights
Written Informed Consent must be obtained inprescribed format from every participant. Theconsent must be signed by patient and Investigatorboth.
Unusual, unexpected or serious ADRs to becommunicated to Licensing Authority and to all
Investigators. Annual Status Reports to be submitted (Ongoing, at
completion / termination)
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Regulatory Documents
Clinical Trial Application (DCGI)
Test License to import study drugs (DCGI)
Export License to export biological samples
(DGFT with NOC from DCGI)
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Clinical Trial Application
Rule 122DA
Application for permission to conduct clinicaltrials for New Drug / Investigational New Drug
should be submitted in Form 44.
Fees payable in cash:Phase I - Rs. 50,000/- Phase II - Rs. 25,000/-
Phase III - Rs. 25,000/-
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Clinical Trial Application
Additional indication / modified dosage form of
an approved drug -Rs. 15,000.00. Approval of a drug one year after its first
approval - Rs. 15,000.00.
Fixed Dose Combination - Rs. 15,000.00.
Modifications related to approved trials e.g.
additional patients / sites - No additional fees
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PROCESSAPPLICATION
FORM 44
-Imp ff
-Imp rm-Mfg ff
-Mfg rm
-CT
NOC FOR CT + Test
Licence forImport
Application Form 46
A (MFG RM)
Approval Form 46
(MFG FF)
Approval Form 45 A
(IMP RM)
Approval Form 45
(IMP FF)
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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
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Application Form 44
FORM 44
(See Rules 122A, 122B, 122D and 122DA)
Application for grant of permission to import or manufacture a New Drug or to undertake clinical trial
I/We.... of .., hereby apply for grant of permission for import and / or clinical trial or forapproval to manufacture of a new drug or fixed dose combination or subsequent permission ofalready approved new drug. The necessary information / data is given below :
1. Particulars of New Drug : Name of the drug : Dosage Form : Composition of the formulation : Test specifications :
Active ingredients :
Inactive ingredients :
Pharmacological classification of the drug :
Indications for which proposed to be used : Manufacturer of the raw material : Patent status :
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FORM 44 Contd
2. Data submitted along with the application
A. Permission to market new drug
1. Chemical and Pharmaceutical information
2. Animal Pharmacology
3. Animal Toxicology
4. Human / Clinical Pharmacology
5. Exploratory Clinical Trials
6. Confirmatory Clinical Trials
7. Bioavailability / dissolution and stability data
8. Regulatory status in othercountries9. Marketing information :
(a) Proposed product monograph
(b) Drafts of labels and cartons
10. Application for test license :
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FORM 44 Contd
D Subsequent approval or approval for new indication new
dosage form :
Number and date of Approval already granted
Justification Data on safety, efficacy and quality
A total fee ofRs has been credited to the
Government under the Head of Account
(receipt enclosed)
Signature
Designation
Date
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FORM 44 Contd
B. Subsequent approval / permission for manufacture ofalready approved new drug
a) Formulation : Bioavailability / bioequivalence
Name of the investigator / centre
Source of raw mat and stability
b) Raw Material
Manufacturing Method QC parameters, specs, stability
Animal toxicity
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FORM 44 Contd
D. Subsequent approval or approval for new indication newdosage form :
Number and date of Approval already granted
Justification
Data on safety, efficacy and quality
A total fee ofRs has been credited to the Government underthe Head of Account (receipt enclosed)
Signature
Designation
Date
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FORM 44 Contd
C. Approval / permission for FDC
Justification
Pcokinetic / Pcodynamic data
Any other data
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Important Considerations - 1
HUMAN CLINICAL PHARMACOLOGY :-
a) Phase I (Human Pharmacology) Safety and Tolerability with the initialadministration of IND MTD, Kinetics and Dynamics
b) Phase II (Therapeutic Exploratory Trials) Effectiveness for a particularindication, small group
c) Phase III (Therapeutic Confirmatory Trials) Therapeutic benefit in large
number of patients
d) Phase IV (Post Marketing Trials) Related to approved indication
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IMPORTANT CONSIDERATIONS
HUMAN CLINICAL PHARMACOLOGY :-
a) for new drug substances discovered in India : Trials are required to be carriedout in india right from phase 1 and required data needs to be submitted.
b) for new drug substances discovered in countries other than India : Phase I datagenerated outside India, permission may be granted to repeat phase 1.
Application for permission to initiate specific phase of clinical trial should alsoaccompany Investigators brochure, proposed protocol, case record form,study subjects informed consent document(s) investigators undertakingand ethics committee clearance, if available
c) Sample size depends on type of study
d) EC application can be in parallel to DCGI application
e) Drugs indicated in life-threatening, serious disease or diseases of specialrelevance to Indian health scenario, toxiciological / clinical data abbreviated,deferred or omitted
f) Administrative/Logistic Amendments notified to DCGI and EC within 30 daysand approval obtained
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Important Considerations - 2
PSUR :-
New drugs should be closely monitored for their clinical safety; submission of PeriodicSafety Update Reports (PSURs) in order to-
report all the relevant new information (patient exposure) summarize the market authorization status in different countries and any
significant variations related to safety; and
indicate whether changes should be made to product information
PSURs shall be submitted every 6 months for the first two years after
approval
For subsequent two years the PSURs need to be submitted
annually
PSURs due for a period must be submitted within 30 calendar days of
the last day of the reporting period.
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IMPORTANT CONSIDERATIONS - 3
BA/BE
i. For drugs approved elsewhere in the world and absorbedsystemically, bioequivalence with the reference formulationshould be carried out.
ii. Evaluation of the effect of food
iii. Dissolution and bioavailability data to be submitted
iv. All bioavailability and bioequivalence studies should beconducted according to the Guidelines for Bioavailability andBioequivalence studies as prescribed (ICMR guidelines)
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TEST LICENCE
Application :
Form 12 application Material Justification Plan
Treasury Challan of Rs 100 for first drug,
followed by Rs 50 for additional drug
Test Licence obtained in FORM 11
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CT Application accompanied by
Proposal Letter
Particulars of New Drug Name ofDrug, dosage form, composition of
formulation, Pharmacological classification,
proposed indication, patent status and
Manufa
cturer
Chemical and Pharmaceutical Data
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CT Application accompanied by
Pre-clinical Data (Animal Pharmacology and
Toxicology).
Clinical Data (Phase I, II and III studies).
Regulatory status in other countries
Published Reports
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CT Application accompanied by
Protocol.
Investigators Brochure
Proposed Sites / Investigators list
Investigators Consent Letters
EC approvals from sites
Application for the Test License in Form 12with justification.
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Test License to Import Drugs
Drugs and Cosmetics Rules 1945Rule 122 DA
Form 11: License to import drugs for thepurpose of examination, test or analysis
Form 12: Application for License to import drugs
for th
e purpose of examination, test or analysis Test License fees - Rs.15/-
Validity of Test License - 1 year
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Importing Drugs for CT
Can be imported by Sponsor / CRO or
investigator Application to be made by respective party
With DCGI approval for study
Justification of quantity to be imported
Renewal required if imports required aftervalidity of license expires
Customs duty payable
IP temp requirements to be followed
during shipment
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Application to DGFT
Required to export biological samples to a centrallaboratory outside India.
Proposal letter
Letter from Sponsor appointing the central laboratory
Letter from the Sponsor stating that no genetic testingwill be done on biological samples
IEC certificate CT NOC
POA
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Application to DGFT
Letter from the central laboratory stating that
only protocol specific laboratory tests will becarried out
Justification for the quantity of biologicalspecimen to be exported
Application package to DGFT & JDGFT (cc) Permission letter issued by DGFT to Sponsor
(cc to JDGFT local issues Export license)
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Renewal of Export License
Export license expires after 1 years
To be applied again within 1 years time forrenewal, timelines 4 6 weeks
Can be renewed twice after fresh application
should be made.
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Application to DGFT
Appendix 16 - Application form for the grantof Export License - 5 copies.
Appendix-2 - Profile of the Exporter
To be submitted once with first application andto be resubmitted in case of any change in the
information already submittedValidity of Export License is one year
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Timelines forRegulatory Approvals
DCGI - 12 to 16 weeks
DGFT - 4 to 6 weeks after DCGI approval
Test-license - 1 week after DCGI approval