IMPORT
OR MANUFACTURE OF NEW DRUG
FOR CLINICAL TRIALS OR
MARKETING
122-A. Application for permission to import New Drug
(1) (a) No new drug shall be imported, except under,
and in accordance with, the permission granted by the Licensing Authority as
defined in clause (b) of rule 21;
(b) An application for
grant of permission to import a new drug shall be made in Form 44 to the
Licensing Authority, accompanied by a fee of fifty thousand
rupees:
Provided further that where a subsequent application
by the same applicant for
that drug, whether in modified dosage form or with new claims, is made, the fee
to accompany such application shall be fifteen thousand
rupees:
Provided further that any application received after
one year of the grant of approval for the import and sale of new drug, shall be
accompanied by a fee of fifteen thousand rupees and such information and data as
required by Appendix 1 or Appendix 1 A of Schedule Y, as the case may be.
;
(2) The importer of a new drug when applying for
permission under sub-rule (1), shall submit data as given in Appendix 1 to
Schedule Y including the results of local clinical trials carried out in
accordance with the guidelines specified in that Schedule and submit the report
of such clinical trials in the format given in Appendix II to the said
Schedule:
Provided that the
requirement of submitting the results of local clinical trials may not be
necessary if the drug is of such a nature that the licensing authority may, in
public interest decide to grant such permission on the basis of data available
from other countries:
Provided further that the submission of requirements
relating to Animal toxicology, Reproduction studies, Teratogenic studies,
Perinatal studies, Mutagenicity and Carcinogenicity may be modified or relaxed
in case of new drugs approved and marketed for several years in other countries
if he is satisfied that there is adequate published evidence regarding the
safety of the drug, subject to the other provisions of these
rules.
(3) The Licensing Authority, after being satisfied
that the drug if permitted to be imported as raw material (bulk drug substance)
or as finished formulation shall be effective and safe for use in the country,
may issue an import permission in Form 45 and/or Form 45 A, subject to the
conditions stated therein:
Provided that the Licensing
Authority shall, where the data provided or generated on the drug is inadequate,
intimate the applicant in writing, and the conditions, which shall be satisfied
before permission, could be considered.
122-B. Application for approval to manufacture New
Drug other than the drugs classifiable under Schedules C and C(1)
(1) (a) No new drug shall be manufactured for sale
unless it is approved by the Licensing Authority as defined in clause (b) of
rule 21.
(b) An application for grant of approval to
manufacture the new drug and its formulations shall be made in Form 44 to the
Licensing Authority as defined in clause (b) of rule 21 and shall be accompanied
by a fee of fifty thousand rupees:
Provided that where the application is for permission
to import a new drug (bulk drug substance) and grant of approval to manufacture
its formulation/s, the fee to accompany such application shall be fifty thousand
rupees only.
Provided further that where a subsequent application
by the same applicant for that drug, whether in modified dosage form or with new
claims, is made, the fee to accompany such subsequent application shall be
fifteen thousand rupees:
Provided further also that any application received
after one year of the grant of approval for the manufacture for sale of the new
drug, shall be accompanied by a fee of fifteen thousand rupees and such
information and data as required by Appendix I or Appendix I A of Schedule Y, as
the case may be.;
(2) The manufacturer of a
new drug under sub-rule (1) when applying for approval to the licensing
authority mentioned in the said sub-rule, shall submit data as given in Appendix
I to Schedule Y including the results of clinical trials carried out in the
country in accordance with the guidelines specified in Schedule Y and submit the
report of such clinical trials in the format given in Appendix II to the said
Schedule.
(2A) The Licensing Authority as defined in clause (b)
of rule 21 after being satisfied that the drug if approved to be manufactured as
raw material (bulk drug substance) or as finished formulation shall be effective
and safe for use in the country, shall issue approval in Form 46 and/or Form 46
A, as the case may be, subject to the conditions stated
therein:
Provided that the Licensing
Authority shall, where the data provided or generated on the drug is inadequate,
intimate the applicant in writing, and the conditions, which shall be satisfied
before permission could be considered.
(3) When applying for
approval to manufacture of a new drug under sub-rule (1) or its preparations to
the State licensing authority, an applicant shall produce along with his
application, evidence that the drug for the manufacture of which application is
made has already been approved by the licensing authority mentioned in Rule
21:
Provided that the
requirement of submitting the result of local clinical trials may not be
necessary if the drug is of such a nature that the licensing authority may, in
public interest decide to grant such permission on the basis of data available
from other countries:
Provided further that the
submission of requirements relating to Animal toxicology, Reproduction studies,
Teratogenic studies, Perinatal studies, Mutagenicity and Carcinogenicity may be
modified or relaxed in case of new drugs approved and marketed for several years
in other countries if he is satisfied that there is adequate published evidence
regarding the safety of the drug, subject to the other provisions of these
rules.
(1) An
application for permission to import or manufacture fixed dose combination of
two or more drugs as defined in clause (c) of rule 122 E shall be made to the
Licensing Authority as defined in clause (b) of rule 21 in Form 44, accompanied
by a fee of fifteen thousand rupees and shall be accompanied by such information
and data as is required in Appendix VI of Schedule Y.
(2) The Licensing Authority after being satisfied
that the fixed dose combination, if approved to be imported or manufactured as
finished formulation shall be effective and safe for use in the country, shall
issue permission in Form 45 or Form 46, as the case may be, subject to the
conditions stated therein:
Provided that the Licensing Authority shall where the
data provided or generated on the fixed dose combination is inadequate, intimate
the applicant in writing, and the conditions which shall be satisfied before
grant of approval/permission could be considered:
122DA. Application for permission to conduct
clinical trials for New Drug/Investigational New
Drug.-
(1) No clinical trial for a new drug, whether for
clinical investigation or any clinical experiment by any Institution, shall be
conducted except under, and in accordance with, the permission, in writing, of
the Licensing Authority defined in clause (b) of rule 21.
(2) An application for grant of permission to
conduct,-
(a) human clinical trials (Phase-I) on a new drug
shall be made to the Licensing Authority in Form 44 accompanied by a fee of
fifty thousand rupees and such information and data as required under Schedule
Y;
(b) exploratory clinical trials (Phase-II) on a new
drug shall be made on the basis of data emerging from Phase-I trial, accompanied
by a fee of twenty-five thousand rupees;
(c) confirmatory clinical trials (Phase-III) on a new
drug shall be made on the basis of the data emerging from Phase-II and where
necessary, data emerging from Phase-I also, and shall be accompanied by a fee of
twenty-five thousand rupees:
Provided that no separate fee shall be required to be
paid along with application for import/manufacture of a new drug based on
successful completion of phases of clinical trials by the
applicant.
Provided further that no fee shall be required to be
paid alongwith the application by Central Government or State Government
Institutes involved in clinical research for conducting trials for academic or
research purposes.
(3) The Licensing Authority after being satisfied
with the clinical trials, shall grant permission in Form 45 or Form 45A or Form
46 or Form 46-A, as the case may be, subject to the conditions stated
therein:
Provided that the Licensing Authority shall, where
the data provided on the clinical trials is inadequate, intimate the applicant
in writing, within six months, from the date of such intimation or such extended
period, not exceeding a further period of six months, as the Licensing Authority
may, for reasons to be recorded, in writing, permit, intimating the conditions
which shall be satisfied before permission could be
considered:
Explanation For the purpose of these rules
Investigational New Drug means a new chemical entity or a product having
therapeutic indication but which have never been earlier tested on human
being.
122DB, Suspension or cancellation of Permission /
Approval.
If the importer or manufacturer under this Part fails
to comply with any of the conditions of the permission or approval, the
Licensing Authority may, after giving an opportunity to show cause why such an
order should not be passed, by an order in writing stating the reasons therefor,
suspend or cancel it.
122DC. Appeal.
Any person aggrieved by an
order passed by the Licensing Authority under this Part, may within sixty days
from the date of such order, appeal to the Central Government, and the Central
Government may after such enquiry into the matter as is considered necessary,
may pass such order in relation thereto as it thinks fit.
122-E. Definition of new drug
For the purpose of this
Part, new drug shall mean and include-
(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.]
Explanation: For the purpose of this
rule-
(i)
all vaccines shall be
new drugs unless certified otherwise by the licensing authority under Rule
21;
(ii)
a new drug shall
continue to be considered as new drug for a period of four years from the date
of its first approval or its inclusion in the Indian Pharmacopoeia, whichever is
earlier.
Form 44
(See rules 122 A, 122 B, 122 D,
and 122 DA)
Application for
grant of permission to import or manufacture a New Drug or to undertake clinical
trial.
*****
I/we
________________________________________________________ of M/s.
_________________________________________________ (address)
hereby apply for grant of permission for import of
and/or clinical trial or for approval to manufacture a new drug or fixed dose
combination or subsequent permission for already approved new drug. The
necessary information / data is given below:
(1)
Name of the
drug:
(2)
Dosage
Form:
(3)
Composition of the
formulation:
(4)
Test
specification:
(i)
active
ingredients:
(ii)
inactive
ingredients:
(5)
Pharmacological
classification of the drug:
(6)
Indications for which
proposed to be used:
(7)
Manufacturer of the raw
material (bulk drug substances):
(8)
Patent status of the
drug:
A. Permission to market a new drug
:-
(1)
Chemical and
Pharmaceutical information
(2)
Animal
Pharmacology
(3)
Animal
Toxicology
(4)
Human/Clinical
Pharmacology (Phase I)
(5)
Exploratory Clinical
Trials (Phase II)
(6)
Confirmatory Clinical
Trials (Phase III) (including published review articles)
(7)
Bio-availability,
dissolution and stability study Data
(8)
Regulatory status in
other countries
(9)
Marketing
information:
(a) Proposed product monograph
(b) Drafts of labels and cartons
(10) Application for test
license
B. Subsequent approval / permission for manufacture
of already approved new drug:
(a) Formulation:
(1) Bio-availability/ bio-equivalence
protocol
(2) Name of the investigator/center
(3) Source of raw material (bulk drug substances) and
stability study data.
(b) Raw material (bulk drug
substances)
(1) Manufacturing method
(2) Quality control parameters and/or analytical
specification, stability report.
(3) Animal toxicity data
C. Approval / Permission for fixed dose
combination:
(1) Therapeutic Justification
(authentic literature in pre-reviewed journals/text
books)
(2) Data on pharmacokinetics/pharmacodynamics
combination
(3) Any other data generated by the applicant on the
safety and efficacy of the combination.
D. Subsequent Approval or approval for new indication
new dosage form:
(1) Number and date of Approval/permission already
granted.
(2) Therapeutic Justification for new claim / modified
dosage form.
(3) Data generated on safety, efficacy and quality
parameters.
A total fee of rupees
__________________________________________ (in words).
____________________________) has been credited to the Government under the Head
of Account ________________________ (Photocopy of receipt is
enclosed).
Dated _____
Signature __________________
Designation ________________
Note- Delete, whichever is not
applicable.
FORM 45
(See rules 122 A, 122 D and 122
DA)
Permission to import Finished
Formulation of a New Drug
Number of the permission and date of issue
_____________________________
M/s
__________________________________________________________ of
______________________________________________________ (address) is hereby
permitted to import the following new drug formulation under rule 122 A/ 122 D/
122 DA of the Drugs and Cosmetics Rules 1945.
(1) Name of the New Drug:
(2) Dosage form:
(3) Composition:
(4) Indications:
Dated
Signature __________________
Name and Designation of the
Conditions for Grant of Approval /
Permission
(1) The formulation shall conform to the specifications
approved by the Licensing Authority.
(2) The proper name of the drug shall be printed or
written in indelible ink and shall appear in a more conspicuous manner than the
trade name, if any, which shall be shown immediately after or under the proper
name on the label of the innermost container of the drug or every other covering
in which the container is packed.
(3) The label of the innermost container of the drug and
every other covering in which the container is packed shall bear a conspicuous
red vertical line on the left side running throughout the body of the label
which shall not be less than 1 mm in width and without disturbing the other
conditions printed on the label to depict it is prescription
drug.
(4) The label on the immediate container of the drug as
well as the packing in which the container is enclosed should contain the
following warning :
WARNING: To be sold by retail on the
prescription of a ________ only.
(5) Post marketing
surveillance study shall be conducted during initial period of two years of
marketing of the new drug formulation, after getting the protocol and the names
of the investigator duly approved by the Licensing
Authority.
(6) All reported adverse
reactions related to the drug shall be intimated to the Drugs Controller, India
and Licensing Authority and regulatory action resulting from their review should
be complied with.
(7) No claims except those
mentioned above shall be made for the drug without the prior approval of the
Licensing Authority.
(8) Specimen of the carton, labels, package insert that
will be adopted for marketing the drug in the country shall be got approved from
the Licensing Authority before the drug is marketed.
(9) Each consignment of imported drug shall be
accompanied by a test/analysis report.
FORM
45 A
(See
rules 122 A and 122 DA)
Permission to import
raw material (new bulk drug substance)
**********
Number of the permission and date of issue
_____________________________
M/s.
__________________________________________________________ of
______________________________________________________ (address) is hereby
permitted to import the following raw material (new bulk drug substances) under
rule 122 A / 122 DA of the Drugs and Cosmetics Rules, 1945,
namely:-
Name of the raw material (new bulk drug
substances):
(1) ___________________
(2) ___________________
(3) ___________________
Dated _____________
Signature __________________
Name
and Designation of the
Conditions for Grant of Approval /
Permission
(1) The raw material (new bulk drug substance) shall
conform to the test specifications as approved by the Licensing
Authority.
(2) For manufacture of raw material (new bulk drug
substance) or its formulations in the country, separate approval under 122-B
shall be obtained from the Licensing Authority.
(3) The permission to import shall not be used to convey
or imply that the raw material (new bulk drug) is categorized as life saving or
essential drug.
FORM 46
(See rules 122 B, 122 D and 122
DA)
Permission/Approval for
manufacture of a new drug formulation
*****
Number of permission and date of issue
_______________________________ M/s.
_________________________________________________________ of
______________________________________________________ (address) is hereby
granted Permission/Approval to manufacture following new drug formulation under
rule 122 B / 122 D / 122 DA of the Drugs and Cosmetics Rules, 1945,
namely:-
(1) Name of the formulation:
(2) Dosage form:
(3) Composition:
(4) Indications:
Dated
Signature
..
Name and designation of Licensing Authority
Conditions for Grant of Approval /
Permission
(1) The formulation shall conform to the specifications
approved by the Licensing Authority.
(2) The proper name of the drug shall be printed or
written in indelible ink and shall appear in a more conspicuous manner than the
trade name, if any, which shall be shown immediately after or under the proper
name on the label of the innermost container of the drug or every other covering
in which the container is packed.
(3) The label of the innermost container of the drug and
every other covering in which the container is packed shall bear a conspicuous
red vertical line on the left side running throughout the body of the label
which shall not be less than 1 mm in width and without disturbing the other
conditions printed on the label to depict it is prescription
drug.
(4) The label on the immediate container of the drug as
well as the packing in which the container is enclosed should contain the
following warning :
WARNING: To be sold by retail on the
prescription of a ________ only.
(5) Post marketing
surveillance study shall be conducted during initial period of two years of
marketing of the new drug formulation, after getting the protocol and the names
of the investigator duly approved by the Licensing
Authority.
(6) All reported adverse
reactions related to the drug shall be intimated to the Drugs Controller, India
and Licensing Authority and regulatory action resulting from their review should
be complied with.
(7) No claims except those
mentioned above shall be made for the drug without the prior approval of the
Licensing Authority.
(8) Specimen of the carton,
labels, package insert that will be adopted for marketing the drug in the
country, shall be got approved from the Licensing Authority before the drug is
marketed.
FORM
46 A
(See
rules 122 B and 122 DA)
Number of the permission and date of issue
_____________________________
Permission / Approval for manufacture of raw material
(new bulk drug substance)
M/s.
__________________________________________________________ of
______________________________________________________ (address) is hereby
granted Permission / Approval to manufacture the following raw material (new
bulk drug substance) under rule 122 B / 122 DA of the Drugs and Cosmetics Rules,
1945:
Name of the raw material (new bulk drug substance):
(1) ___________________
(2) ___________________
(3) __________________
Dated
Signature
Name and Designation of the
Licensing Authority
Conditions for Grant of Permission /
Approval
(1) The raw material (new bulk drug substance) shall
conform to the specifications approved by the Licensing
Authority.
(2) The raw material (new bulk drug substance) can be
sold to only those manufacturers who have permission, in writing, from Licensing
Authority, either to use the drug for development purpose/clinical
trial/bio-equivalence study or to manufacture the
formulation.
(3) For manufacture of the formulation in the country,
separate approval under rule 122-B shall be obtained from the Licensing
Authority.