New Drug Application (NDA)
New Drug Application (NDA) is an application made by the sponsor to the regulatory authorities for approval to sell and market a new drug in different countries. NDA includes enough information for the regulatory authorities to determine whether the new drug is safe and effective; whether the drug’s benefits outweigh its risks; whether the proposed drug label (package insert) is appropriate; and whether the drug manufacturing standards are adequate. NDA can be broadly divided into different steps
New Drug Application (NDA)
The submission of application to conduct clinical trials
Conducting clinical trial
Application to marketing authorization of drug by submitting the data collected from the clinical trials
Post marketing surveillance
New Drug Definition as per the New Clinical Trial Rules, 2019
A new drug means;
Active pharmaceutical ingredient or phyto-pharmaceutical drug, which has not been approved by the Central Licensing Authority (CLA) with respect to its claims; or
Already approved drug but proposed to be marketed with modified or new claims including indication, route of administration, dosage and dosage form; or
A fixed dose combination of two or more drugs which are approved separately for specific indication but now proposed to be
Combined for the first time in a fixed ratio, or
Where the ratio of ingredients is proposed to be changed with certain claims including indication,
Route of administration, dosage and dosage form; or
A modified or sustained release form of a drug or novel drug delivery system of any drug approved by the CLA; or
A vaccine, r-DNA derived product, living modified organism, monoclonal antibody, stem cell derived product, gene therapeutic product or xenografts, intended to be used as drug
The drug approval process in India is governed by CDSCO and the clinical trials should be conducted in accordance to the New Clinical Trial Rules, 2019. For marketing any new drug in the Indian Market, New Drug Application is submitted to CDSCO through the online portal, SUGAM.
Submission of Application
The applicant needs to submit the application by filling Form CT-04 along with all other necessary documents specified under Second Schedule and fees as specified under Sixth Schedule of CT Rules 2019. The data required will depend upon the type of application, phase of the study, stage in drug development process, and/or objective of the study. Following data needs to be submitted along with the NDA.
Pre-clinical data
Clinical data
Drug information
Description of manufacturing procedures
Payment details and transaction ID
Regulatory status in India and in other countries
Details of all sites selected and assessment for suitability of sites and investigators (with contact details)
EC related information including approval letter and EC registration status of the selected sites
Study related document
Central Licensing Authority approval
After reviewing the application, the CLA will either grant the permission to conduct a clinical trial by using form CT-06, or ask the applicant to rectify any deficiency or reject the application by giving reason in writing. In case of rejection, the applicant may request the authorities to reconsider the application within 60 working days from the date of rejection of application. The approval given by the CLA will remain valid for the period of two years from the date of issue, unless extended by CLA.
Time frame for approval:
Upon receipt of the application, the CLA has 90 calendar days to evaluate the application for drugs developed outside India and 30 days for drugs discovered, researched, and manufactured in India. If the CLA does not respond within 30 days to applications for drugs developed in India, the sponsor (applicant) may conclude that permission to conduct the trial has been granted.
Pre-Submission Meeting
Presubmission meetings can be conducted with the CLA or any other officer authorized by the CLA to seek guidance about the requirements of laws and procedures for obtaining license or permission of manufacturing processes, clinical trials and other requirements. The application for a presubmission meeting should be accompanied by documents referred to in the Second Schedule, as available with the applicant to support their proposal along with a fee specified in the Sixth Schedule. CLA, within a period of 30 days, will relate the facts to the applicant in writing and direct them to provide further information or documents as necessary.
Waivers of Local Clinical Trial Data
According to the rule 75, local clinical trials requirements may be waived for import of new drugs. The waiver may be instituted if:
The drug is already approved and marketed in certain countries specified by the licensing authority (Rule 101),
A new drug is approved in certain countries, while global clinical trial for that drug is ongoing in India with no reports of major unexpected serious adverse events and the probability or evidence of differences in the Indian population is negligible with respect to enzymes or genes involved in the metabolism of the new drug or any factor affecting pharmacokinetics (PK) and pharmacodynamics (PD), safety and efficacy of the new drug on the basis of available information. In this case, the applicant will have to conduct a Phase IV study as per design approved by CLA.
The requirement for conducting a Phase IV study may be relaxed in cases where the drug is indicated for life threatening or serious diseases, diseases of special relevance to Indian health scenario, conditions with an unmet need in India, rare diseases for which drugs are not available or available at a high cost or if it is an orphan drug.
New drug that have been approved and marketed for more than two years in other countries, submission of data from animal toxicology, reproduction, teratogenic, perinatal, mutagenicity and carcinogenicity studies may be modified or relaxed.
Clinical Trial Requirement
For new drug application, applicant needs to conduct phase I, Phase II and Phase III trial and submit the data to the CLA for marketing authorization. After getting permission to market the drug, phase IV needs to be conducted.
Approval by the Ethics committee:
Clinical trial shall be initiated at the site only after getting approval letter by the registered Ethics Committee. In case where site is not having a registered Ethics Committee, approval can obtain either from the Ethics committee of other site or Independent Ethics Committee located within the same city or within a radius of 50 kms of the clinical trial site.
Approval granted by the Ethics Committee shall be informed to the CLA within fifteen working days.
Clinical trial shall be registered with the Clinical Trial Registry before enrolling the first subject for the trial;
Clinical trial shall be conducted in accordance with the approved clinical trial protocol and Good Clinical Practices Guidelines
Quarterly submission of the enrollment status as appropriate as per the duration of treatment.
Electronic submission of six monthly status report of each clinical trial to the CLA through SUGAM portal;
Communicating termination of study if any to CLA within 30 working days of termination with reason
Submission of analysis report for serious adverse event (SAE) to CLA and Ethics Committee within 14 days of its occurrence
Compensation and complete medical management should be provided to the subject in case of adverse event or serious adverse event and details of compensation should be submitted to the CLA within 30 working days.
In case of clinical trial related death or permanent disability of any subject during the trial, compensation shall be provided in accordance with Chapter VI and details of compensation provided in such cases shall be intimated to the CLA within thirty working days of receipt of the order issued by the CLA
Inspection of Premises Relating to Clinical Trial
The applicant permitted to conduct clinical trial shall allow the CLA, or officers from CLA to inspect, search or seize, any record, statistical result, document, investigational drug and other related material with or without prior intimation; and reply to queries raised by the inspecting authority in relation to conduct of such clinical trial.
Suspension or Cancellation of Permission to Conduct Clinical Trial
If the applicant permitted to conduct trial fails to comply with any provision of the Act and these rules, the CLA is authorised to issue warning letter describing deficiency, rejects the results or suspend or cancel the permission granted to the applicant, or debar the investigator or sponsor after giving an opportunity to show cause and after affording an opportunity of being heard, by an order in writing. In such case the applicant can make an appeal within 60 working days.
Cliniexperts can help you through the numerous regulations and steps involved in new drug application. CliniExperts provide full spectrum services for the following types of Drug Clinical Trials:
Local Clinical Trial -
Phase I Trial,
Phase II Trial,
Phase III Trialand Phase IV Trial or Post Marketing Studies (PMS) (exclusively in India)Global Clinical Trial -
Phase I Trial,
Phase II Trialand Phase III Trial
Reference
New Drugs and Clinical Trials Rules, 2019, Ministry of Health & Fam. Welfare, Notification, G.S.R. 227(E), (March 19, 2019).