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GUIDELINES FOR FILING ININDIA

AKSHAY DESAI

M.Pharm 2nd semester

Roll no : 18

Department of Quality Assurance

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CONTENT

vINTRODUCTION

v REGULATORY AUTHORITIES

vDRUG APPROVAL PROCESS IN INDIA

v APPLICATION FORM AND PERMISSION

v Application FEES

v IMPORTANT CONSIDERATIONS

v REFRENCE

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Introduction :

Filing of new drug in India required certain guidelines to befollowed by manufacturer

Schedule Y (Requirements AND GUIDELINES for

permission to IMPORT AND / OR MANUFACTUREof New Drugs FOR SALE OR to UNDERTAKECLINICAL TRIALS)of the D & C act must be followed forfiling of new drug

RULES 122A, 122B, 122D, 122DA, 122DB, 122C and 122Emust be followed for new drug import OR manufacture ofnew drug for clinical trials OR marketing

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Drug Approval Process In India

The Drug and Cosmetic Act 1940 and Rules 1945 were passed bythe India's parliament to regulate the import, manufacture,distribution and sale of drugs and cosmetics.

In 1988, the Indian government added Schedule Y to the Drug and

Cosmetics Rules 1945. Schedule Y provides the guidelines andrequirements for clinical trials, which was further revised in 2005

An application to conduct clinical trials in India should be submittedalong with the data of chemistry, manufacturing, control and animal

studies to DCGI.

The date regarding the trial protocol, investigator's brochures, andinformed consent documents should also be attached.

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A copy of the application must be submitted to the ethicalcommittee and the clinical trials are conducted only after approvalof DCGI and ethical committee.

To determine the maximum tolerated dose in humans, adversereactions, etc. on healthy human volunteers, Phase I clinical trialsare conducted.

The therapeutic uses and effective dose ranges are determined inPhase II trials in 10-12 patients at each dose level. The confirmatory trials (Phase III) are conducted to generate dataregarding the efficacy and safety of the drug in ~ 100 patients (in 3-

4 centers) to confirm efficacy and safety claims.

Phase III trials should be conducted on a minimum of 500 patients

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The new drug registration (using form # 44 along with full pre-clinical and clinical testing information) is applied after the

completion of clinical trials

The drug approval process comprised mainly the two steps, 1)Application to conduct clinical trial 2) Application to theregulatory authority for marketing authorization of drug. Sponsor firstly files an application to conduct clinical trial, and onlyafter the approval by the regulatory authority, the applicantconducts the clinical studies and further submits an application to

the regulatory authority for marketing authorization of drug.

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Time, fee and review process of clinical trials and marketingauthorization application differs.

For the purpose of harmonization, the International Conference onHarmonization (ICH) has taken major steps for recommendations inthe uniform interpretation and application of technical guidelinesand requirements

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6/5/12 IND-Investigational New Drug, DCGI-Drug Controller General of India, CDSCO-Centre for Drug Standards Control organization.

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Comparison of Drug approval process.

Country Time forRegulatoryApproval ofCTA/INDApplication

Time forEvaluation ofMAA

MAA Fee

Australia 120 day 50 days $192,400

China 50 days 180 days DNA

India 16-18 weeks 8-12 weeks 50,000 INR

UK* 35 days 210 days 254100

USA 30 days 180 days $217,787

MAA-Marketing Authorization Application,IND-Investigational New Drug,CTA-Clinical Trial Authorization,DNA-Data Not Available.

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Application for permission to import New Drug

Application for approval to manufacture New Drug other than the

drugs classifiable under Schedules C and C(1)

122D. Permission to import or manufacture fixed dose combination

Application for permission to conduct clinical trials for New

Drug/Investigational New Drug.-

Suspension or cancelation of Permission / Approval.

Appeal.

Definition of new drug

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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) ofrule 21

(b) application for grant of permission to import a new drug in Form 44

(2) The importer of a new drug shall submit data as given in Appendix 1 toSchedule Y including the results of local clinical trials(3) The Licensing Authority, after being satisfied that the drug or finished

formulation shall be effective and safe for use in the country, may issue animport permission in Form 45 and/or Form 45 A

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122-B. Application for approval to manufacture New Drug other than the

drugs classifiable under Schedules C and C(1)

Application for grant of permission in Form 44 to the Licensing Authority, as defined inclause (b) of rule 21 issue approval in Form 46 and/or Form 46 A

122D. Permission to import or manufacture fixed dose combination

Application for grant of permission in Form 44 to the Licensing Authority, as defined inclause (b) of rule 21 issue approval in Form 45 or46

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Application for permission to conduct clinical trials for New

Drug/Investigational New Drug.-

Application for grant of permission to conduct,

(a) Human clinical trials (Phase-I) to the Licensing Authority in Form 44 50,000 rs.

(b) Exploratory clinical trials (Phase-II) on a new drug shall be made on the basisof data emerging from Phase-I trial 25,000 rs.

(c) Confirmatory clinical trials (Phase-III) on a new drug shall be made on thebasis of the data emerging from Phase-II and if necessary, data emerging from Phase I

25,000 rs.

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122DB. Suspension or cancelation of Permission / Approval.

If the importer or manufacturer fails to comply with any of the conditions of theLicensing Authority may suspend or cancel

122DC. Appeal.

Any person aggrieved by an order, given by the Licensing Authority within 60days from the date of such order appeal to the Central Government

and if necessary the Central Government may after such enquiry may accept or rejected

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For this part new drug means,(a) New substance in bulk or prepared dosage form; used forprevention,diagnosis, or treatment of disease in man or animal;

(b) Already approved drug by the licensing authority mentioned in Rule 21marketed with modified or new claims, namely, indications, dosage forms

(including sustained release dosage form) and route of administration;

(c) Fixed dose combination of two or more drugs which may be usedindividually earlier but the new combination having better activity &different route of administration

Definition of new drug

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APPLICATION FOR PERMISSION UNDER FORM 44,

REGULATORY AUTHORITIES, FEES AND TEST LICENCE

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IMPORTANT CONSIDERATIONS -1

HUMAN CLINICAL PHARMACOLOGY :-

(a)Phase I (Human Pharmacology) Safety and Tolerability with the initialadministration of IND

(b)Phase II (Therapeutic Exploratory Trials) Effectiveness for a particularindication, small group

(c)Phase III (Therapeutic Confirmatory Trials) Therapeutic benefit in largenumber of patients

(d)Phase IV (Post Marketing Trials) Related to approved indication

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IMPORTANT CONSIDERATIONS -2

PSUR :-

New drugs should be closely monitored for their clinical safety ; submission ofPeriodic Safety Update Reports (PSURs) in order to-

report all the relevant new information (patient exposure)

summarize the market authorization status in different countries and anysignificant variations related to safety; and

indicate whether changes should be made to product information

* PSUR shall be submitted every6 months for the first two years

* after approval For subsequent two years the PSUR need to be submittedannually

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IMPORTANT CONSIDERATIONS - 3

BE / BA

(I )For drugs approved elsewhere in the world and absorbed systemically,bioequivalence with the reference formulation should be carried out.

(ii)Evaluation of the effect of food

(iii) Dissolution and bioavailability data to be submitted

(iv) All bioavailability and bioequivalence studies should be conductedaccording to the Guidelines for Bioavailability and Bioequivalence studies asprescribed (ICMR guidelines)

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RESPONSIBILITIES OF THE SPONSOR

Implementing and maintaining quality assurance systems-Good Clinical Practice (GCP)Guidelines issued byCDSCO, INDIA

Sponsors are required to submit a status report on theclinical trial to the Licensing Authority at the prescribedperiodicity(annual)

In case of studies prematurely discontinued for anyreason including lack of commercial interest in pursuingthe new drug application, a summary report should besubmitted within3 months.

IMPORTANT CONSIDERATIONS 4

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The summary report should provide a briefdescription of the study, the number of patientsexposed to the drug, dose and duration of exposure,details of adverse drug reactions and the reason for

discontinuation of the study or non-pursuit of thenew drug application

Any unexpected serious adverse event (SAE)(asdefined in GCP Guidelines) occurring during a clinical

trial should be communicated promptly(within 14calendar days)by the Sponsor to the LicensingAuthority and to the other Investigator(s)participating in the study

CONTD

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RESPONSIBILITIES OF INVESTIGATOR

Responsible for the conduct of the trial according to the

protocol and the GCP Guidelines and also for compliance

Standard operating procedures are required to bedocumented by the investigators for the tasks performedby them

Ensure that adequate medical care is provided to theparticipant for any adverse events

Report all serious and unexpected adverse events to theS o so w h 24 ho s a d o he E h cs Co ee ha


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RESPONSIBILITIES OF ETHICS COMMITTEE

Safeguard the rights, safety and well being of all trialsubjects

Particular care to protect the rights, safety and well beingof all vulnerable subjects Obtain standard operating procedures and maintain arecord Ongoing review based on periodic study progress reports

In case an ethics committee revokes its approval it must


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REFRENCES


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REFRENCES

1)

www.cdsco

.nic.in/

1) en.wikipedia.org/.../Federal_Food,_Drug,_and_Cosmetic_Act

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