S.R.O. 1047(I)/78, dated 15th July, 1978: In exercise of the powers
conferred by Section 43 of the Drugs Act, 1976 (XXXI of 1976),
the Federal Government is pleased to make the following rules,
the same having been previously published as required by sub-section
(3) of the said section, namely :-
1. Short title and commencement:
(1) These rules may be called the Drugs (Research) Rules, 1978.
(2) They shall come into force at once,
2. Definitions: In these rules, unless there
is anything repugnant in the subject or context,-
(a) "Committee" means the Committee of Experts constituted
under rule 8;
(aa) "form" means form appended to these rules;
(b) "Fund" means the Central Research Fund maintained
by the Federal Government under sub-rule (14) of rule 19 of the
Drugs (Licensing, Registering and Advertising), Rules, 1976;
(c) "investigator" means a person engaged in the investigation,
research, development or evaluation of a drug on his own initiative
or under the sponsorship of any other person or an institution;
(d) "recipient" means a person or an institution who
or which receives aid from the Fund; and
(e) "sponsor" means a person, firm, an establishment
or institution promoting research on a drug.
3. Utilisation of Fund: The Federal Government
may utilise the Fund for conducting research, development or evaluation
of a drug either itself or through a research institution working
under its control or disburse it among investigators or institutions
for such purposes subject to such conditions as may be specified
and for that matter, it may also utilize the fund to upgrade and
establish Drugs Research and testing laboratories and a unit in
the Drugs Control Section, Ministry of Health, for evaluation
and monitoring of the research proposals and projects and management
of the fund.
4. Research in drugs: The research in drugs shall be
conducted at such place or places and by such person or persons
as may be approved by the Federal Government and shall be categorised
as under :--
(i) other than clinical trials; and
(ii) clinical trials.
5. Application for grant of aid: (1) An application
for the grant of aid from the Fund for conducting research on
a drug on aspects other than the clinical trials and for clinical
trials shall be made in Form 'A' and Form 'B', respectively, and
addressed to the Secretary of the Committee.
(2) The Federal Government may, before granting any aid from the
Fund, cause inspection of the premises concerned end technical
evaluation of the project by the Committee or any expert appointed
by it for this purpose.
(3) The Federal Government may, after obtaining the advice of
the Committee and subject to such conditions as it may specify
in this behalf, grant such aid from the Fund to a person or an
institution as it may deem fit.
6. Conditions for conducting research on aspects of other
than clinical trials: (1) The research on any aspect
of drugs other than clinical trial shall be conducted under the
supervision of an investigator who possesses post-graduate qualification
and experience in the relevant field and has sufficient background
knowledge to conduct scientific investigation.
(2) The recipient shall, at regular intervals not exceeding six
months, submit the progress report to the Federal Government in
respect of the investigation being conducted.
(3) No change of an investigator or in the plan for investigation
shall be made without prior approval of the Federal Government.
(4) The recipient shall allow an expert or a panel of experts
authorised by the Federal Government to visit the premises at
which the research is being conducted and to see that the Fund
is being utilised in accordance with the approved plan.
7. Conditions for research in clinical trials:
(1) In addition to the conditions laid down in rule 6, research
in drugs on aspect of clinical trials shall be conducted in the
following stages:-
(i) Stage 1 of investigation on human beings shall consist of
studies to determine single and short term multiple dosing for
tolerance, side effects, toxicity, metabolism, preferred routes
of administration, safe dosage range and other pharmacological
actions of the drug:
Provided that these studies shall be conducted under carefully
controlled circumstances on comparatively small number of subjects
to prevent any serious deleterious effect on health.
(ii) Stage II of investigation shall consist of studies to determine
safety and effectiveness including an effective dose range, the
common side effects of the drug on both clinical and laboratory
parameters and where possible the level of drug in biological
fluids in relation to therapeutic response:
Provided that these studies shall be undertaken if studies in
Stage I of investigation demonstrate satisfactory results and
shall involve initial and limited use of the drug in the treatment
or prevention of the disease for which the drug is intended and
shall be administered to carefully supervised patients:
Provided further that the Federal Government may require additional
pharmacological studies to be conducted concurrently on animals
to indicate safety for stage II of the investigation.
(iii) Stage III of investigation shall consist of studies under
controlled conditions in order to expand knowledge of potential
use and hazards and shall be undertaken if the data obtained in
stages I and II provide reasonable assurance of safety and effectiveness
or suggest that the drug may have a potential value of conducting
several trials outweighing its hazards:
Provided that these studies shall be carefully monitored and all
possible precautions shall be taken to prevent unnecessary exposure
of the patient to the risk.
(2) If at any stage there appears to be an unwarranted hazard
in the continuation of the ongoing clinical trials, the sponsor
and recipient may be asked by the Federal Government to modify
or discontinue clinical trials until further pre-clinical work
has been done and the investigator conducting such research shall
discontinue further tests under intimation to the sponsor and
the recipient in writing, a copy of which be sent to the Federal
Government.
(3) Studies on children shall not be undertaken unless there is
a possibility of benefit to them and adequate studies of safety
and efficacy are available in adults.
(4) When any dangerous or adverse effects are observed, emergency
reports shall be sent immediately by the recipient to the Federal
Government so that the other investigators are informed and the
studies are stopped if the hazard so warrants.
(5) The consent for use of all investigational new drugs in clinical
trials for stages I and II shall be obtained in writing by the
investigator but for stage III it is the responsibility of the
investigator to take into consideration the physical and mental
state of the patient to decide when it is necessary or preferable
to obtain consent other than in writing and if written consent
is not obtained, the investigator, must obtain oral consent and
record the fact in the medical record of the person receiving
the drug.
(6) The recipient shall keep the record of his studies carefully
in respect of every drug, retain it for at least ten years after
registration of that drug and produce it before the Federal Government
whenever required.
8. Committee of Experts on Drug Research: (1)
The Federal. Government shall set up a Committee of Experts on
Drug Research to determine the priorities, to give directions
in drug research, to evaluate the applications received for the
grant and make allocations from the .Fund and to take or propose
such actions and measures as may be necessary for ensuring effective
and proper use of the Fund:
(1) The Federal Government shall constitute a Committee of Experts
to advise it on the utilisation of the Fund and for such other
purposes as may be necessary for the proper utilisation of the
Fund.
(2) The Committee shall consist of the following members namely
:-
(a) Director-General Health who shall be its ex-officio Chairman.
(b) Executive Director, National Institute of Health, Islamabad.
(c) Chairman of the Pharmacy Department who shall hold office
for three years by rotation. Chairman, Pharmacy Department, Peshawar
University shall be the member for the first term.
(d) Chairman of the Pakistan Council of Scientific and industrial
Research or his nominee who may be directly responsible for drugs
research activities in the Council.
(e) Chairman of the Pakistan Medical Research Council, or his.
nominee who may be directly responsible for drugs research activities
in the Council.
(f) A Dean of the Pharmacy Faculty who shall hold office for three
years by rotation. Dean of the Pharmacy Faculty, University of
Karachi, shall be the member for the first term.
(g) A Professor of Pharmacology who shall hold office for three
years by rotation. Professor of Pharmacology Allama Iqbal Medical
College, Lahore, shall be the member for the first term.
(h) One representative of the Pakistan Pharmaceutical Manufacturers'
Association (PPMA) who may be well-versed with the subject and
actively engaged in the planning or conducting of research on
drugs.
(i) Drugs Controller, Ministry of Health, Islamabad.
(j) Deputy Director General Health (Research and Development),
Ministry of Health, Islamabad, who shall be its ex-officio Secretary.
(3) The Federal Government may appoint a Secretary of the Committee
from amongst its members.
9. Withdrawal of Fund and termination of an investigation:
(1) The Federal Government may, at any stage of an investigation,
withdraw the aid from the recipient and direct him and the sponsor
to terminate a clinical trial under any of the following conditions,
namely :-
(i) evidence of significant hazard;
(ii) convincing evidence that the drug is ineffective;
(iii) submission of false data;
(iv} omission of material information pertaining to safety or
efficiency of the drug;
(v) unsatisfactory manufacturing practices;
(vi) failure to conduct the investigation in accordance with plan
submitted and approved by the Federal Government;
(vii) commercialization of the drug before completing clinical
trial;
(viii) failure to report serious or potentially serious adverse
reaction;
(ix) failure to meet the requirement of patient's consent; and
(x) evidence of misuse of the Fund:
Provided that the Federal Government may, before withdrawing the
aid, require the recipient and the sponsor of any drug to comply
with any of the above conditions which he has failed to comply
within a specified period and may, after it is satisfied that
the said conditions have been compiled with, allow resumption
of the investigation.
FORM 'A'
[See rule 5 (1)]
Application for grant of aid for conducting research in drugs
other than clinical trials
1. Name and address of the applicant.
2. Name and address of the sponsor if he is other than the applicant.
3. Title of Research project.
4. Financial implications of the project.
(i) Total Financial implications.
(ii) Present investment.
(iii) Other sources of finance. if any
(iv) Amount required from the Drugs Research Fund and details
of its proposed
utilisation.
5. Details of the Research project as follows :--
(i) Purpose.
(ii) Outline.
(iii) Progress already made (if any).
(iv) Comprehensive future Plan.
(v) Benefits.
6. Bio-data of all investigators including Incharge of the Research
project giving the name. qualifications with years and experience.
FORM 'B'
[See rule S (l)]
Application for grant of aid for conducting clinical trials
1. Name and address of the applicant.
2. Name and address of the sponsor if he is other than applicant.
3. Title of Research project.
4. Financial implications of the project:
(i) Total Financial implications.
(ii) Present Investment.
(iii) Other sources of finance, if any.
(iv) Amount required from the Central Research Fund and details
of its proposed utilisation.
5. Enclose herewith--
(i) outline of the Research Project, its purpose, benefits, description
of the comprehensive plans. and progress already made, if any
:
(ii) information and data about the drug to be investigated including
its exact composition, chemistry. pharmacology, toxicity, conditions
for use in man, and pharmacy with special reference to the method
of manufacture and quality control to show that adequate standards
exist and a meaningful assessment can be made of the safety of
the material for use in man (copies of all informational material
to be supplied to the investigator should be enclosed);
(iii) results of pre.clinical investigation including animal studies
directed towards defining its safety and efficacy; and
(iv) an agreement from the sponsor and the applicant that they
shall notify the Federal Government and all investigators if they
become aware of any adverse effect arising during the course of
investigation.
Note: When an investigator himself wishes to act as sponsor conducting
an investigation, the amount of information required under item
4 (ii) and (iii) may vary but should be sufficient to identify
the compound under investigation together with the facts which
satisfy that the substance may be justifiably administered to
human beings with reasonable margin of safety.
6. Bio-data of all investigators including Incharge of the Research
project giving the name, qualifications and experience.
