\n License for or\n Registration Certificate<\/strong>\n <\/td>\n Form for Application<\/strong>\n <\/td>\n Form for Grant<\/strong>\n <\/td>\n Relevant Rule<\/strong>\n <\/td>\n Validity of License\n (from date of application)<\/strong>\n <\/td><\/tr>| \n Ethics\n Committee for Clinical Trial\n <\/td> | \n Form CT-01\n <\/td> | \n Form CT-02\n <\/td> | \n CT Rule 8\n <\/td> | \n 5 years\n <\/td><\/tr> | | \n Permission\n to conduct clinical trial of a new drug or investigational new drug\n <\/td> | \n Form CT-04\n <\/td> | \n Form CT-06\n <\/td> | \n CT Rule 21, CT Rule 22\n <\/td> | \n 2 years\n <\/td><\/tr> | | \n Permission\n to conduct clinical trial of a new drug or investigational new drug as part\n of discovery, research and manufacture in India (Deemed approval)\n <\/td> | \n Form CT 4A\n <\/td> | \n Form CT 4A\n <\/td> | \n CT Rule 23\n <\/td> | \n 2 years\n <\/td><\/tr> | | \n Permission\n for conducting BA\/BE studies\n <\/td> | \n Form CT 05\n <\/td> | \n Form CT 07\n <\/td> | \n CT Rule 33, CT Rule 34\n <\/td> | \n 1 year (subject to extension)\n <\/td><\/tr> | | \n Permission\n to manufacture new drug or investigational new drug for clinical trial or\n BA\/BE study or for examination, test and analysis\n <\/td> | \n Form CT 10\n <\/td> | \n Form CT 11\n <\/td> | \n CT Rule 52, CT Rule 53\n <\/td> | \n 3 years\n <\/td><\/tr> | | \n Permission\n to manufacture unapproved active pharmaceutical ingredient for development of\n formulation for test or analysis or clinical trial or BA\/BE study\n <\/td> | \n By Manufacturer of formulation in Form CT 12\n & \n By manufacturer of API in Form CT 13\n <\/td> | \n To Manufacturer of formulation in Form CT 14\n &\n To Manufacturer\n of formulation in Form CT 15\n <\/td> | \n CT Rule 59, CT Rule 60\n <\/td> | \n 3 years\n <\/td><\/tr> | | \n Import\n of new drug or IND for clinical trial or BA\/BE study\n <\/td> | \n Form CT 16\n <\/td> | \n Form CT 17\n <\/td> | \n CT Rule 67, CT Rule 68\n <\/td> | \n 3 years\n <\/td><\/tr> | | \n Import\n of new drug for sale or distribution\n <\/td> | \n Form CT 18\n <\/td> | \n Permission to import API in Form CT 19 Permission to\n import pharmaceutical formulation in Form CT 20\n <\/td> | \n CT Rule 75, CT Rule 76\n <\/td> | \n \n <\/td><\/tr> | | \n Manufacture\n of new drug for sale or distribution\n <\/td> | \n Form CT 21\n <\/td> | \n Manufacture of API in Form CT 22 Manufacture of\n pharmaceutical formulation in Form CT 23\n <\/td> | \n CT Rule 80, CT Rule 81\n <\/td> | \n \n <\/td><\/tr> | | \n Import\n of unapproved new drug by Government hospital and medical institution\n <\/td> | \n Form CT 24\n <\/td> | \n Form CT 25\n <\/td> | \n CT Rule 86, CT Rule 87\n <\/td> | \n \n <\/td><\/tr> | | \n Manufacture\n of unapproved new drug under clinical trial, for treatment of patient with\n life threatening disease\n <\/td> | \n Form CT 26\n <\/td> | \n Form CT 27\n <\/td> | \n CT Rule 91, CT Rule 92\n <\/td> | \n 1 year\n <\/td><\/tr><\/tbody><\/table>\n\n\n\n<\/span>Data Safety Monitoring Board<\/span><\/h2>\n\n\n\nWhile\na clinical study is in progress, this impartial team of specialists keeps an\neye on the participant safety and treatment efficacy data. Top priority of the\nboard is the safety of the patient. The DSMB would advise stopping the trial if\nsignificant adverse events were to occur more often in the experimental arm\nthan in the control arm. The risk against benefit ratio must be taken into\naccount while making this assessment. In many instances, the experimental\ntherapy might result in negative side effects while undergoing treatment, such\nas chemotherapy for some terminal cancers.<\/p>\n\n\n\n <\/span>2019\nNew Drugs and Clinical Trials Rules: Major Changes<\/strong><\/span><\/h2>\n\n\n\nFollowing\nare some of the major changes made by the New Drugs and Clinical Trials\nRules of 2019: <\/strong><\/p>\n\n\n\nAcademic Clinical\nTrials<\/strong><\/em><\/strong><\/em><\/p>\n\n\n\nAcademic\nclinical trials are defined by the New Rules, 2019<\/em> as clinical trials of\na drug already approved for a certain claim initiated by any investigator,\nacademic or research institution for a new indication, new route of\nadministration, new dose, or new dosage form, where the results of such a trial\nare intended to be used only for academic or research purposes and not for\nseeking approval of the Central Licensing Authority or regulatory authority of\nany country for marketing or commercial purpose. <\/p>\n\n\n\nThe\nfollowing are some key considerations for academic clinical trials:<\/p>\n\n\n\n - Only for\nauthorised medications<\/li>
- CT\nstarted by a researcher, academic institution, or research centre<\/li>
- Can be\ndone for a novel indication, a novel route, a novel dose, or a novel dosage\nform.<\/li>
- Results\nshould only be used for academic or research purposes; not for profit. In no\nnation may data be used to request approval.<\/li>
- The\nCentral Licensing Authority (CLA) must answer to EC’s request for clarification\nwithin 30 days (or deemed that no approval is needed)<\/li>
- In\naccordance with the ICMR Guidelines for Biomedical Research on Human\nParticipants, medical management and compensation are appropriate.<\/li>
- The\nEC-approved CT protocol and the ethical standards outlined in the ICMR\nGuidelines for Biomedical Research on Human Participants must be followed while\nconducting academic CTs.<\/li><\/ul>\n\n\n\n
The\nmainstay of basic research is academic clinical investigations, including\nInvestigator Initiated Clinical Trials (IICT) and research done during\npost-graduate programmes in colleges. While it is the responsibility of the\nhost institution to provide compensation and\/or cover for compensation in cases\nof injury in Academic CT and Biomedical and Health Research (BHR), the Ethics\nCommittee (EC) is responsible for the relatedness of Serious Adverse Events\n(SAE) and recommendation of appropriate compensation. However, as the ICMR\nGuidelines do not include a provision for compensation calculation, it would be\ndifficult for ECs to establish the amount of compensation. Therefore, there is\na critical necessity to create standards for calculating the amount of\ncompensation.<\/p>\n\n\n\n Pre-submission\nMeeting<\/strong><\/em><\/em><\/p>\n\n\n\nIn\norder to explore a regulatory pathway for a particular application, CDSCO\ndecided in January 2015 to implement a system of formal pre-submission meetings\nwith applicants, CDSCO officers, and subject experts. The final paper was\npublished, but it was never put into practise because this was against the\nregulations, and there were no following actions.<\/p>\n\n\n\n The\nNew Rules, 2019 do, however, include a clause allowing for pre-submission\nmeetings with the CLA or any other officer designated by the CLA to get advice\non the legal requirements and processes for obtaining licences or permissions\nfor manufacturing processes, clinical trials, and other requirements. The\nSecond Schedule papers, if any are available with the applicant to support\ntheir proposal, should be submitted with the application for a pre-submission\nmeeting, together with the fee listed in the Sixth Schedule. Within 30 days,\nCLA will communicate the facts to the applicant in writing and instruct them to\nsupply any further information or documentation that may be required.<\/p>\n\n\n\n These\nnew regulations offer a chance to talk about regulatory channels for product\nregistration, much like with authorities in industrialised nations. Before a\ncompany begins to prepare its regulatory filing, this opportunity aims to\nclarify the roadmap. This modification may also be beneficial in situations\nwhen enterprises spend funds on studies that are not supported by the relevant\nauthorities or in situations where certain studies are required from a\nregulatory standpoint but are not carried out.<\/p>\n\n\n\n Pre-submission\nmeetings would give corporations with written guidance that, up until then, was\nbased solely on conversations with a small number of regulatory officials.<\/p>\n\n\n\n Revising\nNew Drug Definition<\/strong><\/em><\/strong><\/em><\/p>\n\n\n\nThe\nfollowing has been added to the definition of \u2018new drugs\u2019:<\/p>\n\n\n\n - Plant-based\npharmaceuticals<\/li>
- Novel\nmedication delivery method for any substance<\/li>
- Xenografts,\nmonoclonal antibodies, stem cell-derived products, gene therapeutics, and\nliving modified organisms are all intended for use as drugs.<\/li><\/ul>\n\n\n\n
Phase IV and Post-marketing Studies (PMS)<\/strong><\/p>\n\n\n\nThe definition and\nspecifications for Phase IV and PMS were unclear in the past. The conditions\nfor completing Phase 4 CT and post-marketing monitoring studies for new drugs have\nbeen differentiated under the New Rules of 2019.<\/p>\n\n\n\n The 2019 New Rules\nPhase IV Study will cover research on:<\/p>\n\n\n\n - Medication\ninteractions<\/li>
- Research on safety or\ndose-response<\/li>
- Experiments made to\nsupport usage for the permitted indications<\/li><\/ul>\n\n\n\n
Post-marketing\nsurveillance studies<\/strong><\/p>\n\n\n\nThese\nresearch projects employ a novel drug under authorised usage guidelines and\nwith a CLA-approved scientific goal. The prescription information or authorised\npackage insert’s recommended usage determines whether subjects are included or\nexcluded. In these trials, the patient receives the study medicines as prescribed\nby the doctor as part of their treatment. The regulatory requirements and\ncriteria that apply to a clinical study of a new medicine do not apply to drugs\nthat have already received marketing approval.<\/p>\n\n\n\n Ethics Committees (ECs)<\/strong><\/p>\n\n\n\nAccording\nto the new regulations, ECs must include at least one female member and 50% of\nits membership must be made up of people who are not connected to the\ninstitution or group that formed the committee. Furthermore, each EC member\nmust complete any training and development programmes that CLA may occasionally\nspecify under the new guidelines. Additionally, any modification to the\nmembership or organisational structure of a registered E must be disclosed in\nwriting to CLA within 30 working days. Before accepting any new CTs for review,\nECs must undergo reconstitution (and subsequently re-registration) to conform to\nthe new regulations.<\/p>\n\n\n\n Waivers of Local Clinical Trial Data<\/strong><\/p>\n\n\n\nFor the import of novel pharmaceuticals, Rule 75\nspecifies the circumstances under which the obligation for local clinical\ntrials may be waived. The waiver may be implemented if the following conditions\nare met: the drug is approved and marketed in certain countries specified by\nthe licencing authority (Rule 101), a global clinical trial is currently being\nconducted in India with the drug, and in the interim, and such new drug has\nbeen approved in certain countries specified by the licencing authority (Rule\n101). Additionally, the waiver’s implementation\nmandates that there be no likelihood or evidence based on current knowledge of\nvariations in the Indian population, enzymes or genes involved in the new\ndrug’s metabolism, or any other factor affecting the pharmacokinetics (PK) and\npharmacodynamics (PD), safety, and efficacy of the new drug. In this situation,\nthe applicant will have to carry out Phase IV research in accordance with the\nplan certified by CLA. In situations where the drug is indicated for\nlife-threatening or serious illnesses, illnesses with particular relevance to\nthe Indian healthcare system, illnesses with unmet needs in India, rare\nillnesses for which there are no or very expensive treatments, orphan drug\ndesignations, the requirement for conducting a Phase IV study may be waived. In\nthe case of novel pharmaceuticals that have been licenced and marketed for more\nthan two years in other countries, data submission from animal toxicity,\nreproductive, teratogenic, perinatal, mutagenicity, and carcinogenicity studies\nmay be adjusted or eased.<\/p>\n\n\n\n In\naccordance with the circumstances outlined in Rule 80, authorisation to\nmanufacture novel medications may be granted without conducting local clinical\ntrials (local products). The requirements are nearly identical to those for new\ndrug imports, with the exception that data submission from animal toxicology, reproduction,\nteratogenic, perinatal, mutagenic, and carcinogenicity studies may be modified\nor relaxed in cases where new drugs have been approved and have been on the\nmarket for a number of years in other countries.<\/p>\n\n\n\n These\nclauses take into consideration the fact that a regulatory body in another\nnation has already reviewed and approved the new medicine. This clause may\nshorten the period of time between a drug’s global introduction and its\neventual availability to patients in India.<\/p>\n\n\n\n Other\nsignificant updates<\/strong><\/strong><\/p>\n\n\n\nA\nclause in the New Rules of 2019 allows for the expedited licencing of new drugs\nthat are designed to treat conditions of particular significance to India or to\naddress a medical need there, particularly in the event of a disaster or for\nspecific defence purposes. If exceptional effectiveness had been noted in this\ncase, marketing authorisation may be given based on Phase II clinical evidence.\nHowever, under these circumstances, a Phase IV clinical study will be required\nto confirm any predicted therapeutic advantages.<\/p>\n\n\n\n For\ndrug compounds and formulations intended to be held under general circumstances\nfor a long time, conditions for obtaining stability data have been updated from\nZone IV (a) to Zone IV (b). The long-term stability conditions have been changed\nfrom 30\u00b0C 2\u00b0 C\/65% RH 5% RH to 30\u00b0C 2\u00b0 C\/75% RH 5% RH as per Zone IV(b).<\/p>\n\n\n\n Timelines\nfor new clinical study approvals have also been included. The CLA has 90\nworking days to react about clinical trials for medications created outside of\nIndia. However, if the medicine was discovered in India, is currently\nundergoing research and development there, and is planned to be produced and\nmarketed there, the review period may be further shortened to 30 working days.\nFor BA\/BE studies of new medications or investigational new pharmaceuticals\nwithin 90 working days of application receipt, authorization to conduct a\nclinical trial should be presumed to have been granted if no notification is\nreceived from the CLA.<\/p>\n\n\n\n For\nimproved functionality and monitoring, this timeline has been altered in\naccordance with the new CT regulations. In the absence of a revised\nnotification from CLA, authorization to conduct a clinical study for a novel or\ninvestigational medicine within 90 days of the application’s receipt shall be presumed\nto have been granted.<\/p>\n\n\n\n <\/span>What Is Clinical Trial\nRegistry<\/span><\/h2>\n\n\n\nClinical\ntrials have a great deal of potential to help patients, enhance therapy\nregimens, and guarantee the development of evidence-based medical practise. To\nrestore public confidence in clinical trial data, all clinical studies must be\nregistered in a single, centralised clinical trials registry. This will\nguarantee openness, accountability, and accessibility.<\/p>\n\n\n\n Presently, any researcher who is planning to conduct a\nclinical trial involving human of any intervention for example, drugs, surgical\nprocedures, preventive measures, lifestyle modifications or the trials being\nconducted under the Department of AYUSH are required to register the\nclinical trial in the CTRI (Clinical trial registry \u2013 India) before enrolment\nof the first participant. Before the first patient is enrolled for the clinical\ntrial, the trial’s investigators, sponsors, interventions, patient population,\netc. must be publicly declared and identified.<\/p>\n\n\n\n <\/span>CTRI-\nA Brief History<\/span><\/h2>\n\n\n\nThe Central Licensing Authority also called as CLA made\nclinical trial registration in the CTRI mandatory as of June 15, 2009. The CTRI\nwas first introduced on July 20, 2007, initially as a voluntary measure. The\nCTRI’s goal is to make it possible for all clinical trials carried out in India\nto be prospectively registered before the first participant is enrolled.\nBioavailability\/bioequivalence studies and post-marketing monitoring studies\nmust also be reported in the CTRI. The Department of Science and Technology (DST),\nICMR, and WHO all come together to fund CTRI.<\/p>\n\n\n\n <\/span>What Is The Process Of\nRegistering A Clinical Trial?<\/span><\/h2>\n\n\n\nIf\nyou wish to register a clinical trial, you must follow the steps mentioned\nbelow: <\/p>\n\n\n\n - Register yourself on the CTRI website and create your profile. Once this\nis done then you can move forward with the registration of the trial.<\/li>
- New clinical trial is then added using the CTRI registration data set\n(information regarding the data set has been discussed below.)<\/li>
- The above data set is then submitted to CTRI.<\/li>
- After receiving all the information CTRI will give a reference number of\nthe clinical trial. <\/li>
- CTRI will verify the data set and trial form PI <\/li>
- Once the CTRI is satisfied from the information, it will provide a unique registration number.\nThis number has to be used while submitting your study in any journal. <\/li><\/ul>\n\n\n\n
<\/span>Information Required For\nClinical Trial Registration<\/span><\/h2>\n\n\n\nThe CTRI data set which needs to be submitted during the\nprocess of registering is mentioned below: <\/p>\n\n\n\n - Study\ntitle in simple language <\/li>
- Scientific\ntitle of the study (Acronym, if any) <\/li>
- Secondary\nID which includes any Protocol Number or any other Trial Registry Number,\nregistered in a registry other than the CTRI. <\/li>
- Details\nof the Principal Investigator which includes heir name, official address,\naffiliation and designation, contact details and email ID. <\/li>
- Details\nof the person for scientific query and person for public query<\/li>
- List of\nsources for the monetary support as well as material support<\/li>
- Details\nof primary and secondary sponsor(s)<\/li>
- Details\nof site(s) of study <\/li>
- Name of\nEthics Committee and approval status<\/li>
- Regulatory\nclearance obtained from CLA<\/li>
- Details\nregarding the inclusion and exclusion criteria for participant selection,\nincluding age and sex<\/li>
- Target\nsample size<\/li>
- Details\nregarding the Phases of trial<\/li>
- Date of\nfirst enrolment<\/li>
- Estimated\nduration of trial<\/li>
- Recruitment\nstatus of trial<\/li><\/ul>\n\n\n\n
<\/span>Benefits of Clinical Trials\nRegistration<\/span><\/h2>\n\n\n\n- Enhance openness and accountability<\/strong>: The public’s trust in clinical trials is likely to be increased by revealing all necessary information on the protocol of studies.<\/li>
- Increasing the trials’ internal validity:<\/strong> During the restoration of the experiment, it will be necessary to disclose the mechanism used to generate the random sequences, hide participant allocation to treatments adequately, blind participants, investigators, and outcome assessors adequately, and include the outcomes of all participants. These trial procedures are especially crucial for producing accurate results by reducing biases, confounders, and the impact of chance or coincidence. Such inclusions at the protocol stage are likely to improve the trial’s internal validity and raise the likelihood that it will be published in a high impact journal.<\/li>
- Adhere to moral norms that are widely accepted:<\/strong>
- It will assist in providing ethical review boards with a glimpse of comparable work and data pertinent to the study they are evaluating when deciding whether to approve new trials.<\/li>
- All clinical studies must have approval from their local ethics committees in order to be registered.<\/li><\/ul><\/li>
- Accurate reporting of all pertinent findings from registered trials<\/strong>: All results from registered trials shall be properly documented and made available to the public.
- Registration of clinical trials will stop selective publishing and selective reporting of results.<\/li>
- It will stop pointless study effort duplication.<\/li>
- It may be simpler to spot gaps in clinical studies by describing ongoing clinical trials and research<\/li>
- Recruitment may be facilitated by informing researchers and potential participants about recruitment trials.<\/li>
- Collaboration between researchers might be improved by giving practitioners and researchers the ability to discover studies in which they might be interested. Future meta-analysis may be a part of the partnership. Patients and the general public will benefit from knowing which studies are upcoming or currently underway and could be of interest to them.<\/li><\/ul><\/li>
- For publishing consideration: <\/strong>Editors of 11 prominent biomedical journals in India and publications that are members of the International Committee for Medical Journal Editors (ICMJE) now need registration in a public trials register as a condition for publication. Trials must register at the start of patient enrolment or earlier.<\/li><\/ol>\n\n\n\n
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