A MINOR PROJECT REPORT ON

WORLDWIDE COMPREHENSIVE STUDY ON GUIDELINE OF CLINICAL TRIAL

PRESENTED BYSALAMTULLAH KHAN

EN.NO. – 0149PY10MP54SUPERVISOR CO-SUPERVISOR

DR. N P S SENGAR MR. DHARMENDRA SHUKLA

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1-INTRODUCTIONObjective:-

Gain a comprehensive overview of the regulatory requirements for carrying out clinical trials

Ensure compliance in regulatory requirements for investigational medicinal products, pharmacovigilance, and Clinical Trial Data Management including EDC and e-source

Explore recent developments in clinical trial regulations including FDA requirements

Achieve successful regulatory inspections.

Introduction of clinical trial:-

Clinical research is the key to the discovery of latest diagnostic methods and to develop modern drugs for treatment of diseases. Good Clinical Practices (GCP) is an ethical and scientific quality standard for designing, conducting and recording trials that involve the participation of human subjects.

Clinical trial protocol:- A clinical trial protocol is a document

that describes the objective(s), design, methodology, statistical considerations, and organization of a clinical trial

A clinical trial protocol is a document used to gain confirmation of the trial design by a panel of experts and adherence by all study investigators, even if conducted in various countries.

Pre-clinical studies:-

It involves in vitro(test tube or cell culture) and in vivo(animal) experiments using wide ranging doses of the study drug to obtain preliminary efficacy, toxicity and pharmacokinetics information.

Phases:- Clinical trials involving new drugs are

commonly classified into four phases. 1-Phase 0:- is a recent designation for

exploratory, first in human trial conducted in accordance with the USFDA 2006 Guidance on Exploratory IND Studies.

Phase I:- trials are the first stage of testing in human subjects. Normally, a small (20-100) group of healthy volunteers will be selected. This phase includes trials designed to assess the safety (pharmacovigilance), tolerability, pharmacokinetics, and pharmacodynamics of a drug.

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Phase II:- Once the initial safety of the study drug has been confirmed in Phase I trials, Phase II trials are performed on larger groups (100-300) and are designed to assess how well the drug works, as well as to continue Phase I safety assessments in a larger group of volunteers and patients.

Phase III:- studies are randomized controlled multicenter trials on large patient groups (300–3,000 or more depending upon the disease/medical condition studied) and are aimed at being the definitive assessment of how effective the drug is, in comparison with current 'gold standard' treatment.

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Phase IV :-trial is also known as Post marketing surveillance Trial. Phase IV trials involve the safety surveillance (pharmacovigilance) and ongoing technical support of a drug after it receives permission to be sold.

Phase V:- is a growing term used in the literature of translational research to refer to comparative effectiveness research and community-based research; it is used to signify the integration of a new clinical treatment into widespread public health practice.

Administration:-

Clinical trials designed by a local investigator and (in the U.S.) federally funded clinical trials are almost always administered by the researcher who designed the study and applied for the grant.

Phase III and Phase IV clinical trials of new drugs are usually administered by a contract research organization (CRO) hired by the sponsoring company.

Regulatory agencies:-

If a clinical trial concerns a new regulated drug or medical device (or an existing drug for a new purpose), the appropriate regulatory agency for each country where the sponsor wishes to sell the drug or device is supposed to review all study data before allowing the drug/device to proceed to the next phase, or to be marketed.

Locating trials:-

Depending on the kind of participants required, sponsors of clinical trials use various recruitment strategies, including patient databases, newspaper and radio advertisements, flyers, posters in places the patients might go (such as doctor's offices), and personal recruitment of patients by investigators.

2-Worldwide Background Introduction

Good Clinical Practice for Clinical Trial in India:-

Submission of Clinical Trial Application for Evaluating Safety

and Efficacy:-

The clinical trial sponsor is required to submit application (Form 44) for the purpose of conducting clinical trial in India and submit documents as per Schedule Y of the Drugs and Cosmetics Act 1940 .

Good Clinical Practice Guidelines issued by CDSCO, Directorate General of Health Services, Govt. of India

Submit two hard copies and two soft copies:-

Hard copies:- It must be well labeled with document number, name of the firm, date of submission etc.

Soft Copies:- They must be well labeled with document number, name of the firm, date of submission etc. Scanned copies of only signed document like test reports will be acceptable as soft copies.

SECTION A: GENERAL INFORMATION:-

Introduction about Company Administrative Headquarters Manufacturing Facilities Regulatory permissions/approvals Regulatory and intellectual property

status in other countries Patent information status in India &

other countries

SECTION B:CHEMISTRY MANUFACTURING CONTROL

Product Description Product Development Information on Drug Substance Production of Drug substance Characterization of Drug substance Information on Drug Product. - Description & composition Components of Drug product Equipment and Premises

Carrying out Clinical Trials in India

India now participates in over 7% of all global Phase III and 3.2% of all global Phase II trials1.

Clinical trial outsourcing market in India is forecast to grow at a compound annual growth rate of over 30% during 2010-2012 to around $600 million by 2012.

USFDA CLINICAL TRIAL GUIDELINE

Application for FDA approval to market a new drug:- 

Three copies of the application are required: An archival copy, a review copy, and a field copy. An application for a new chemical entity will generally contain an application form, an index, a summary, five or six technical sections, case report tabulations of patient data, case report forms, drug samples, and labeling, including, if applicable, any Medication Guide required

Investigational new drug application:-

Investigational New Drug Application:-clinical investigation is not permitted to proceed without the prior written authorization from FDA. FDA shall provide a written determination 30 days after FDA receives the IND or earlier.

Responsibilities of Sponsors and Investigators

Institutional Review board:-

clinical investigations regulated by the Food and Drug Administration. as well as clinical investigations that support applications for research or marketing permits for products regulated by the Food and Drug Administration

Each IRB shall have at least five members,

ICH GUIDELINE CLINICAL TRIALIndependent ethics committee

Responsibilities. Composition, Functions and

Operations. Procedures. Records.

Clinical trial protocol and protocol amendments

General Information Background Information Trial Objectives and Purpose Trial Design Selection and Withdrawal of Subjects Treatment of Subjects Assessment of Efficacy Direct Access to Source Data/Documents Quality Control and Quality Assurance Data Handling and Record Keeping

EUROPEAN UNION CLINICAL TRIAL GUIDELINE

Request for a clinical trial authorization

Request for authorization, applicable timelines, authorization

Interface with other authorization requirements

Cover letter Clinical trial application form Protocol Investigator’s brochure

Notification of amendments and related measures

Ethics Committee shall give an opinion within a maximum of 35 days of the date of receipt of the proposed amendment in good and due form. If this opinion is unfavorable, the sponsor may not implement the amendment to the protocol.

Declaration the end of a clinical trial

The sponsor has to make an end of trial declaration when the complete trial has ended in all Member States/third countries concerned.

The end of trial notification, albeit usually submitted only subsequently to the end of trial notification. The sponsor should provide this summary report within one year of the end of the complete trial for non-paediatric clinical trials.

3-LITERATURE SURVEY Bleichner G et al (1986) work on Frequency of

infections in cirrhotic patients presenting with acute gastrointestinal haemorrhage.

Lamont JP et al (2003) work on A randomized trial of valved vs nonvalved implantable ports for vascular access.

Bien CG et al (2004) work on An open study of tacrolimus therapy in Rasmussen encephalitis.

Christian G. Bien et al (2009) work on Efficacy of Tacrolimus and I.V.-

Mouterde G et al (2010) work on Indications of glucocorticoids in early arthritis and rheumatoid arthritis

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Likosky DS et al (2010) work on The effect of the preoperative blood transfusion and blood conservation in cardiac surgery .

Robertson D et al (2010) work on SOGC clinical practice guidelines.

Flint HE et al (2010) work on How well do reports of clinical trials in the orthodontic .

Carson G et al (2010) work on Alcohol use and pregnancy consensus clinical guidelines.

Tolmie EP et al (2011) work on Clinical Trials: Minimising source data queries to streamline endpoint adjudication in a large multi-national trial.

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Welch RW et al (2011) work on There is substantial evidence to link what we eat to the reduction of the risk of major chronic diseases and/or the improvement of functions.

Parsons NR et al (2011) work on A systematic survey of the quality of research reporting in general orthopaedic journals.

Wong S et al (2011) work on SOGC clinical practice guidelines: Substance use in pregnancy.

Nankervis H et al (2011) work on Mapping randomized controlled trials of treatments for eczema.

4-RESEARCH ENVISAGED

International Phase I clinical trials with new chemical entities developed in a foreign country (first-in-human trials) are not allowed in India.

prevent the fake clinical trial in India because the fake clinical trial is real problem occur.

It should less time taken of the clinical trial approval in India.

It should be inspected by drug controller government of India.

5-PLAN OF WORK

Brief Study about clinical trial Guideline. Comparison for Guideline of various

country. How possible variation in clinical trial

guideline in India. Study about spurious clinical trial in India How possible to stop fake clinical trial in

India . find out the literature survey.

6-CONCLUSION

After comprehensive study of the USFDA and ICH guideline I will find out the some differences like as;

International Conference on Harmonization (ICH) Guideline covering the conduct of clinical research studies in the seven member nations. Guidelines represent the agency's current thinking on Good Clinical Practices, but do not bind the FDA or the public.

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IRB:-ICH requires that the clinical investigator provide the Institutional Review Board (IRB) with a copy of the Investigator Brochure (4.4.2). FDA only requires that the pharmaceutical company sponsor provide it to the investigator.

Documentation of Protocol Deviations:-ICH requires that the investigator document and explain any deviation from the study protocol (4.5.3). FDA does not address this issue.

Informed Consent:-The elements differ between ICH (4.8.10) and FDA (50.25a, 50.25b).

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Financial Records:- Signed Protocols:- Indemnification:- Case Report Form Changes:-

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THANKYOU