regulatory requirements for clinical trial

7/28/2019 Regulatory Requirements for Clinical Trial

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Regulatory Requirement for Clinical Trial

Regulatory Requirement for ClinicalTrial

10/02/2010

Domain: Pharma KPO

Author:Arun [email protected]

TCS Internal
mailto:[email protected]:[email protected]:[email protected]


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Purpose

The purpose of this document is to facilitate the user to understand the RegulatoryRequirement for Clinical Trials

Introduction

Regulatory requirements are part of the process ofdrug discovery and drugdevelopment. Regulatory requirements describe what is necessary for a new drug to beapproved for marketing in any particular country.

In the US, it is the function of the Food and Drug Administration (FDA) to establishthese regulatory requirements. The European Medicines Agency (EMEA) and JapanesePharmaceuticals and Medical Devices Agency (PMDA) are also important regulatoryauthorities in drug development. These three agencies oversee the three largestmarkets for drug sales

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http://en.wikipedia.org/wiki/Drug_discoveryhttp://en.wikipedia.org/wiki/Drug_developmenthttp://en.wikipedia.org/wiki/Drug_developmenthttp://en.wikipedia.org/wiki/Food_and_Drug_Administrationhttp://en.wikipedia.org/wiki/European_Medicines_Agencyhttp://en.wikipedia.org/wiki/Japan_Ministry_of_Healthhttp://en.wikipedia.org/wiki/Japan_Ministry_of_Healthhttp://en.wikipedia.org/wiki/European_Medicines_Agencyhttp://en.wikipedia.org/wiki/Food_and_Drug_Administrationhttp://en.wikipedia.org/wiki/Drug_developmenthttp://en.wikipedia.org/wiki/Drug_developmenthttp://en.wikipedia.org/wiki/Drug_discovery


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Following are the regulatory requirement from FDA for ClinicalTrials.

Electronic Records &Electronic Signature (21 CFR Part11)

Protection Of Human Subjects(Informed Consent (21CFR PART 50)

Financial Disclosure by Clinical Investigators (21 CFR PART 54)

Institutional Review Boards (21 CFR PART 56)

Investigational New Drug Application (21CFR PART 312

Bioavailability and Bioequivalence Requirements (21 CFR PART 320)

* Electronic recordmeans any combination of text, graphics, data, audio, pictorial orother information representation in digital form that is created, modified, maintained,archived, retrieved, or distributed by a computer system.

*Electronic signature means a computer data compilation of any symbol or series ofsymbols executed, adopted, or authorized by an individual to be the legally bindingequivalent of the individual's handwritten signature.

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Protection of Human Subjects(Informed Consent(21CFR PART50)

Under this no investigator may involve a human being as a subject in researchcovered by these regulations unless the investigator has obtained the legallyeffective informed consent of the subject or the subject's legally authorizedrepresentative. An investigator shall seek such consent only undercircumstances that provide the prospective subject or the representativesufficient opportunity to consider whether or not to participate and thatminimize the possibility of coercion or undue influence. The information that isgiven to the subject or the representative shall be in language understandableto the subject or the representative

Basic elements of informed consent: In seeking informed consent, thefollowing information shall be provided to each subject:

A statement that the study involves research An explanation of the purposes of the research The expected duration of the subject's participation A description of the procedures to be followed Identification of any procedures which are experimental. A description of any reasonably foreseeable risks or discomforts to the

subject.

A description of any benefits to the subject or to others which mayreasonably be expected from A disclosure of appropriate alternativeprocedures or courses of treatment, if any, that might be advantageousto the subject.

A statement describing the extent, if any, to which confidentiality ofrecords identifying the subject will be maintained and that notes thepossibility that the Food and Drug Administration may inspect therecords.

For research involving more than minimal risk, an explanation as towhether any compensation and an explanation as to whether anymedical treatments are available if injury occurs and, if so, what theyconsist of, or where further information may be obtained.

An explanation of whom to contact for answers to pertinent questionsabout the research and research subjects' rights, and whom to contact inthe event of a research-related injury to the subject.

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Financial Disclosure by Clinical Investigators (21 CFR PART 54)

The requirements in this part apply to any applicant who submits a marketingapplication for a human drug, biological product, or device and who submits coveredclinical studies. The applicant is responsible for making the appropriate certification ordisclosure statement where the applicant either contracted with one or more clinicalinvestigators to conduct the studies or submitted studies conducted by others notunder contract to the applicant

Institutional Review Boards (21 CFR PART 56)

This part contains the general standards for the composition, operation, andresponsibility of an Institutional Review Board (IRB) that reviews clinical investigationsregulated by the Food and Drug Administration under sections 505(i) and 520(g) of theact, as well as clinical investigations that support applications for research or marketingpermits for products regulated by the Food and Drug Administration, including foods,including dietary supplements, that bear a nutrient content claim or a health claim,infant formulas, food and color additives, drugs for human use, medical devices forhuman use, biological products for human use, and electronic products. Compliancewith this part is intended to protect the rights and welfare of human subjects involvedin such investigations. Each IRB shall have at least five members, with varyingbackgrounds to promote complete and adequate review of research activitiescommonly conducted by the institution.

Investigational New Drug Application (21CFR PART 312)

This part contains procedures and requirements governing the use of investigationalnew drugs, including procedures and requirements for the submission to, and reviewby, the Food and Drug Administration of investigational new drug applications.

Investigational new drug means a new drug or biological drug that is used in a clinicalinvestigation (This application is based on pre-clinical data, typically from animal studies,that shows the drug is safe enough to be tested in humans.)

The New Drug Application (NDA) is the vehicle in the United States through which drugsponsors formally propose that the FDA approve a new pharmaceutical for sale andmarketing.The goals of the NDA are to provide enough information to permit FDA reviewers toestablish the following:

Is the drug safe and effective in its proposed use(s) when used as directed, anddo the benefits of the drug outweigh the risks?

Is the drugs proposed labeling (package insert) appropriate, and what should itcontain?

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http://en.wikipedia.org/wiki/United_Stateshttp://en.wikipedia.org/wiki/Food_and_Drug_Administrationhttp://en.wikipedia.org/wiki/Drughttp://en.wikipedia.org/wiki/Package_inserthttp://en.wikipedia.org/wiki/Package_inserthttp://en.wikipedia.org/wiki/Drughttp://en.wikipedia.org/wiki/Food_and_Drug_Administrationhttp://en.wikipedia.org/wiki/United_States


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Are the methods used in manufacturing (Good Manufacturing Practice, GMP)the drug and the controls used to maintain the drugs quality adequate to

preserve the drugs identity, strength, quality,and purity?

Bioavailability and Bioequivalence Requirements (21 CFR PART320)

Bioavailability means the rate and extent to which the active ingredient is absorbed from adrug product and becomes available at the site of action. For drug products that are notintended to be absorbed into the bloodstream, bioavailability may be assessed bymeasurements intended to reflect the rate and extent to which the active ingredient oractive moiety becomes available at the site of action.

Drug product means a finished dosage form, e.g., tablet, capsule, or solution that containsthe active drug ingredient, generally, but not necessarily, in association with inactiveingredients

Bioequivalence means the absence of a significant difference in the rate and extent towhich the active ingredient or active moiety in pharmaceutical equivalents orpharmaceutical alternatives becomes available at the site of drug action whenadministered at the same molar dose under similar conditions in an appropriatelydesigned study. Where there is an intentional difference in rate (e.g., in certainextended release dosage forms), certain pharmaceutical equivalents or alternatives maybe considered bioequivalent if there is no significant difference in the extent to whichthe active ingredient or moiety from each product becomes available at the site of drugaction. This applies only if the difference in the rate at which the active ingredient ormoiety becomes available at the site of drug action is intentional and is reflected in theproposed labeling, is not essential to the attainment of effective body drugconcentrations on chronic use, and is considered medically insignificant for the drug.

*IN INDIA CDSCO IS THE DRUG REGULATORY AUTHORITY

Function of CDSCO(Central Drug Standard Control Organization)

Approval of New Drug and Clinical Trials Import Registration and Licensing Testing of Drugs Banning of Drugs and Cosmetics

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http://en.wikipedia.org/wiki/Good_Manufacturing_Practicehttp://en.wikipedia.org/wiki/Good_Manufacturing_Practice


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Approval of Clinical Trials, Import, & Manufacture of New Drugs

Requirements and Guidelines - Schedule Y Rule 122 A Permission to import new drug Rule 122 B Permission to manufacture new drug Rule 122 DA Definition of Clinical trials Rule 122 E Definition of New Drugs* New substance having therapeutic indication Modified or new claims, new route administration for already approved drug Fixed Dose Combination

IMPORT, REGISTRATION AND LICENSING

Manufacturing sites and Products are required to be Registered Rules 21 to 30 Rules related to grant of Registration Certificate and Import

License

Schedule DI & DII Information required for registration of Mfg site and Product Registration Certificate(RC) and Import License - Valid for 3 years

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GUIDANCE FOR INDUSTRY

Submission of Clinical Trial Application for Evaluating Safety and Efficacy Requirements for permission of Drugs Approval Post approval changes in biological products: Quality safety and Efficacy

Documents

Preparation of the Quality Information for Drug Submission for Drug

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http://cdsco.nic.in/CDSCO-GuidanceForIndustry.pdfhttp://cdsco.nic.in/CDSCO-GuidanceForIndustry.pdf