1. INTRODUCTION TO DRUG REGULATORY SYSTEM.
Drug Regulation means the control of Drug by regulatory authority to ensure safety efficacy quality of drug.
This is achieved by following and practicing the good practices in pharmaceutical

2. Science. Integration and convergence of the following good practices are necessary to achieve quality safety and efficacy of the molecule for the desired therapeutic purpose.
The concerned good practices are
Good clinical practice GCP
Good Manufacturing Practice GMP

3. Good Laboratory practice GLP
Good Storing practice GSP
Good Transport Practice GTP
Good Pharmacy Practice GPP

4. STEPS TO UNDERGO FOR A CHEMICAL MOIETY TO QUALITY AS DRUG MOLECULE
Plant source in crude from
synthetic drugs
already Known to have Therapeutic Efficacy and are in use as Ayurvedic system of Medicine Siddha and Herbal drug
Structure determination
Synthetic analogs leading to number of drug molecules
Identification , Solvent extraction & Purification
Structure Activity Relation study (SAR) QSAR Study
Structure determination
Synthetic of side chain SAR /QSAR Study

5. *# MOLECULES SELECTED TO UNDERGO CLINICAL STUDY ON HUMAN SUBJECTS
Synthesis of side chain and SAR/QSAR study ***
No. of compounds SAR/QSAR study ***
*** [Pharmacological and Therapeutic activity determination
ED 50 / LD 50 study / therapeutic index Study
Toxicity study /Genotxicity / Repoductive study
General pharmacological screening with special study on the biological organ having specific pharmacological activity. ] *#
*# MOLECULES SELECTED TO UNDERGO CLINICAL STUDY ON HUMAN SUBJECTS

6. On the basis of the aforesaid guideline Molecules are selected for clinical study on human subjects for conducting clinical trial (under good clinical practice) GCP on the basis of written permission with all conditions as the case may be from authorized competent person ( i.e Drug Controller General of India – DCG India.

7. UNDER 122 DA D & C RULE – Application for permission to conduct clinical trial/ Investigational new drug.
Under 122 E of D &C rule– Definition of new drug A new drug shall mean and include
a) A drug as defined in the act including bulk drug substance which has not been used in the country to any significant extent under the

8. Conditions prescribed, recommended or suggested in the labeling there of and has not been recognized as effective and safe by the licensing authority mentioned under rule 21 for the proposed claims.
Provided that the limited use, if any has been with the permission of the licensing authority.

9. 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, dosage form (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

10. 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 the ingredients in an already marketed combination is proposed to be changed, with certain claims viz. indications, dosage, dosage form (including sustained release dosage form) and route of administration.

11. For purpose of this rule
All vaccines and recombinant DNA(RDNA) derived drugs shall be new drugs unless. certified otherwise by the licensing authority ii) A new drug shall continue to be considered as new drug for period of four years from the date of

12. RULE 122 DAA – DEFINITION OF CLINICAL TRIAL
its first approval or its inclusion in the India pharmacopoeia whichever is earlier.
RULE 122 DAA – DEFINITION OF CLINICAL TRIAL
Clinical trial means a systemic study of new drugs in human subject(s) to generate data for discovering and/or verifying the clinical, pharmacological (inducing pharmacodynamics

13. and pharmacokinetic ) and /or adverse effects with the objective of determining safety and or adverse effects with the objective of determining safety and/or efficacy of a new drug.

14. SCHEDULE Y OF DRUGS & COSMETICS RULE & GOOD CLINICAL PRACTICE GUIDELINES FOR CLINICAL TRAILS IN INDIA.
It aims to ensure that the studies are (a) scientifically and ethically sound and that the clinical properties of the pharmaceutical substances under investigation are properly documented
The guidelines seek to establish two cardinal principles (i) protection of the rights of human subjects and

15. (ii) Authentically of the biomedical data generated
(ii) Authentically of the biomedical data generated. These guidelines have been evolved with consideration of WHO/ ICH /USFDA and European GCP as well as the Ethical Guidelines for Biomedical Research on Human subject issued by Indian council of Medical Research.
At all stages of drug development these guidelines should be followed.

16. CLINICAL RESEARCH ORGANIZATION (CRO)
An organization to which the sponsor may transfer delegate some or all of the tasks duties/obligation regarding the clinical trial.
All such contractual transfers of obligations should be defined in writing.
A CRO is a scientific body commercial, academic or other.

17. RESPONSIBILITY OF SPONSOR
(a) Clinical trial sponsor is responsible for
(i) quality assurance system
(ii) Data generated according to protocol
(iii) Standard operative procedure
(b) required to prepare status report in clinical trial to licensing authority.

18. In case of studies prematurely discontinued a summary report should be submitted within 3 months.
(d) Any unexpected serious adverse event (SAE) should be communicated within 14days by the sponsor to the L.A and to other investigators.

19. RESPONSIBILITIES OF THE INVESTIGATORS
To conduct trial according to protocol and GCP guidelines
The investigator should ensure that adequate medial care is provided to the participant for any adverse event to the sponsor within 24 hrs. and to Ethic committee that accorded approval to the study protocol within 7 working days.

20. INFORMED CONSENT
Both the informed consent form and the patient information sheet should have been approved by the ethics committee and furnish to the licensing authority.
For unconscious patient/minor/mentally disabled person, legally acceptable representative should give the consent.

21. RESPONSIBILITY OF THE ETHICS COMMITTEE
Ethics committee is responsible to protect the right, safety and well being of the subjects participating in the study.
Ethics committee should met at appropriate intervals and review the trials and protocol.
In case of revoking the approval, the reasons for doing so should be recorded and informed to the LA.

22. Composition of Independent Ethics committee (IEC) consists of 7-8 members.
Chairperson
1-2 basic medical Scientifics ( preferably one pharmacologist)
1-2 Clinicians
One legal expert or retired judge
One social scientist.
One philosopher/ ethicist
One lay person from the community
One member secretary.

23. STUDIES CONDUCTED IN PHASE -I
Investigational New Drug (Phase -I)
Objective – safety and tolerability with initial administration studies conducted in Phase -I
STUDIES CONDUCTED IN PHASE -I
Maximum tolerability of the dose range and to determine the nature of adverse reaction that can be expected.
Studies include both single and multiple dose administration.

24. INVESTIGATIONAL NEW DRUG (PHASE -I)
(c) Pharmacokinetics ie. Characterization of a drugs absorptive, distribution, metabolism and excretion
(d) To determine pharmacokinetic parameters in different age groups to support dosage recommendation.
(e) Potential therapeutic benefits may be conducted in phase I study as a secondary objective.

25. THERAPEUTIC EXPLORATORY TRIALS (PHASE –II)
To evaluate the effectiveness of a drug for the particular indication and to determine the short term side effect.
An important goal for this phase is to determine the dosage and regimen for Phase –III study.
If the application is for conduct of clinical trials as a part of multinational climical development in India the justification of such trial in India shall be explained

26. THERAPEUTIC CONFIRMATORY TRAILS (PHASE -III)
The Primary objectives is confirmation of therapeutic benefits.
To further reconfirm that the primary evidence generated in phase II that the drug is safe and effective for intended use.
To further explore the also dose response ,the drug concentration in blood and clinical response. Further use of the drug to a wider population.

27. Safety and efficacy of the drug in combination with other drug.
d) Safety and efficacy of the drug in Indian patients. Licensing authority may require pharmacokinetic studies to be under taken to verify that data generated in Indian population is in confirmatory will data already generated abroad.
e) In case of multinational clinical trials, no of sites in India as well as justification shall be provided to the LA along with application.

28. POST MARKETING TRIALS (PHASE -IV)
These trials go beyond the prior demonstration the drug’s safety, efficacy and dose definition.
These trials may not be considered necessary at the time of new drug approval but may be necessary by L.A. for optimizing the drug’s use.
b) Phase –IV trails include (i) additional drug drag interactions (ii) dose response or safety studies and trials designed to support use under approved indications.

29. GERIATRICS STUDIES IN SPECIAL POPULATION
Geriatric patents should be included in Phase –III Clinical trials ( and in phase II trials at the sponsor’s option.) in meaning full numbers.
i) If disease intended to be treated is characteristically a disease of aging. Or
ii) Population to be treated include substantial number of geriatric patients or.

30. iii) Specific reason to expect that conditions common in the elderly are likely to be encountered or.
iv) When the new drug is likely to alter the geriatric patients response (with regard to safely or efficiency) compared with that of non geriatric.

31. PEDIATRICS
For a drug expected to be used in children, evaluation should be mode in the appropriate age group.
It is usually appropriate to begin with older children before extending the trial to younger children and the infants.

32. iii) The pediatric studies should include
Clinical trials
Relative bioequivalence comparisons of the pediatric formulation with the adult formulation performed in adults.
Definitive pharmacokinetic studies for dose selection across the age ranges of pediatric patients.
Pediatric subjects are legally unable to provide written informed consent, and are dependent on their

33. PREGNANT OR NURSING WOMEN
Parents/ legal guardian to assume responsibility for their participation in clinical studies.
Written informed censer should be obtained from the part/legal guardian.
PREGNANT OR NURSING WOMEN
a) Pregnant or nursing women should be included in clinical trials only when the drug in intended for use by pregnant /nursing women or foetuses, nursing infants

34. and where the data generated from women who are not pregnant or nursing is not suitable.
b) New drug intended for use during pregnancy, follow-up data (pertaining to the period appropriate for that drug) on the pregnancy, foetus and the child will be required.
e) Where applicable, excretion of the drug or its metabolites in human milk should be examined and the infants should be monitored for predicted pharmacological effects of to drug.

35. POST MARKETING SURVEILLANCE
(Period safety Update Reports) PSUR
Subsequent to approval of the product, new drug should be closely monitored for their clinical safety once they are marketed.
The PSUR shall be submitted every six month for first two years after approval is granted.
For subsequent two years the PSUR need to be submitted annually.

36. L.A may extend the total duration of study if it is considered necessary in the public interest.
A PSUR should be structured as follows:-
Title page applicants name period covered, date of approved / date of marketing.
Introduction

37. c) Current world wide market authorization status
d) Update of actions taken for safety reasons information.
e) Changes to reference safety information.
f) Estimated patient exposure
g) Presentation of individual case histories

38. h) Other information
i) Overall safety information
j) Conclusion
k) Appendix  providing material relating to indications dosing pharmacology and other related information.

39. SPECIAL STUDIES : BIOAVAILABILITY BIOEQUIVALENCE
i) For drugs approved elsewhere in the world and absorbed systemically bioequivalence should be carried out. Data on the extent of systemic absorption may be required for formulations other the those designed for systemic absorption.

40. iii) Dissolution and bio availability data submitted with new drug application must provide information that assures bioequivalence or established bioavailitiblty and dosage co relations between the formulation soft to be marketed and those used for clinical trials during clinical development of the product.
iv) All bioavailability bioequivalence studies should be conducted as per guidelines. For bioavailability and bioequivalence studies as prescribed.