How to get DCGI NOC without query - I
Though no official guidelines have been published CROs and Sponsors have been receiving deficiency letters from DCGI. We depict some important points to be kept in mind while drafting protocols, ICF for clinical trials and the supportive documents that should be provided along with DCGI NOC application so as to obtain DCGI NOC without queries.
Though no official guidelines have been published CROs and Sponsors have been receiving deficiency letters from DCGI. we depict some important points to be kept in mind while drafting protocols, ICF for clinical trials and the supportive documents that should be provided along with DCGI NOC application so as to obtain DCGI NOC without queries.
- Study Related Injury and Compensation: As the concern is more on study related injury and compensation, please ensure that these areas are addressed as per ethical guidelines and Indian regulatory requirements in appropriate sections of your protocols and ICF's.
- Study Related Injury: The onus on study related injury will be with the organisation that's applying for NOC. If the application is delegated through a CRO by the sponsor then statements should be mentioned in appropriate sections of the protocol and ICF that In case of study related injury {CRO Name} will provide complete medical care along with compensation for injury. If NOC is applied through sponsor, then the sponsor should take the responsibility of study related injury and compensation.
- Compensation: As feedbacks reveal that the subjects/patients are not compensated proportionately for their participation in the trial you are requested to add the following statement in protocol and ICF, Compensation for participation in the study will be paid proportionately at the end of each period of the study.
- Age limit: As the probability of getting an insurance reimburisement in the event of death/disease decreases with ages beyond 45 yrs, (you are required to undergo a medical test with the insurance agency designated doctor, if you are above 45 years of age) the agency now wants studies to be performed with subject within an age limit of 18 - 45 yrs both inclusive. Note: A thorough literature research should be done before deciding on the same. If a different range is desirable (e.g. safety issues) the same should be communicated to the regulatory authorities with supportive data.
- No of Subjects: Sponsors/CROs should provide proper justification for the number of subjects to be recruited for the trial. Though this should be justifiable for a clinical trial its not the same with bioequivalence study. If you are proposing a subject size of more than 50 for a bioequivalence study, you are sure to get a query to justify the same. This is fair, as a subject size of 40 should be more than sufficient to prove bioequivalence with sufficient power for a non highly variable drug. A higher number of subject number for a bioequivalence study, may raise doubts of forced bioequivalence at the cost of drug exposure to subject. If you are to include subjects more than 50 for any study it's advisable to provide proper justification for the same with ISCV from pilot data or with reference to published literature. If you are skeptic about your pivotal fortunes you may propose an arbitrary sample size in pivotal protocol and mention that the sample size will be finalized based on pilot study results.
- IEC Approval: The DCGI now wants the active participation of IEC/IRB in the NOC process of the trial. As per new requirement only IEC approved protocols should be included in application of DCGI NOC. All ethical committees (if formed as per regulatory requirements) will have a doctor/lawyer/Layperson/Scientist in place as its members. DCGI feels that the IEC would have thoroughly reviewed the protocol and if any issues relating to safety of subjects were present, objection would have been raised and deficiencies resolved before IEC approval of the protocol.
- IEC Approval Process: All the documents with respect to IEC application, composition and approval should be enclosed. The minutes of the IEC meeting should be documented along with the DCGI NOC application. This will give a brief idea to DCGI about objections raised with regards to protocol and ICF if any, and the resolution of the same before approval.
- Methods used to recruit volunteers for the study: During IEC approval CROs are to provide the details of methods used for volunteer recruitment for that study, which includes but are not limited to advertisements, hand outs etc. DCGI has now made it mandatory to provide the same during NOC application so as to scrutinize for any fiddling claims to woo the subjects into the trial.
- Informed consent process followed for the study: Sponsors/CROs are to provide the informed consent process that will be followed during the study. They will have to submit the ICF forms to be used in the trial along with NOC application. Presentations and questionnaires that will be provided to the subjects during the Informed consent process are also to be provided during the NOC application. Note: Many CROs are providing their SOPs on volunteer recruitment, Informed consent process and IEC approval process for the requirements Nos. 5, 6 & 7 discussed above. But it's not as
- The same SOPs would have been audited by the DCGI during CRO facility approval.
- The same documents would be recycled for all NOCs applied through that CRO, which is quiet ridiculous.
Read More
0
comments
Notification to DCGI regarding amendment to approved protocol
DCGI feels due to lack of clarity applications received for amendment to approved protocol of clinical trials are incomplete and lot of avoidable correspondence is being carried out. DCGI has come up with guidelines on notification to the agency regarding amendment of approved protocol.
DCGI has come up with guidelines on notification to the agency regarding amendment of approved protocol. Changes made to the Protocol and resultant amendments effected needs to be informed to the DCGI.
Amendments are categorised into three categories,
- Those amendments which do not require any infomation or permission.
- Those amendements which require to be infomed but need not wait for permission.
- Those amendments which require prior permission before implementation of the amendments.
A. Amendments that does not require notification to or permission of the Licensing Authority
- Administrative and Logistic changes.
- Minor protocol amendments and additional safety assessments in case the institutional ethics committee has already approved these changes.
B. Amendments that require notification to the Licensing Authority but need not wait for permission
- Additional Investigator sites.
- Change in investigator with the consent to withdraw from the earlier investigator.
- Amended Investigators Brochure, amended informed consent.
C. Amendments that require prior permission of the Licensing Authority
- Additional Patients to be recruited.
- Major changes in protocol with respect to study design, dose and treatment options.
- Any change in inclusion or exclusion criteria.
Read More
0
comments
Submission of additional bioequivalence study Data for ANDAs - New FDA Requirment
FDA regulations now require report of all bioavailability or bioequivalence studies conducted during drug development. FDA believes it will increase understanding of generic drug development which in turn will promote further development of science-based bioequivalence policies.
FDA regulations now require submission of either a summary report or a complete report of all bioavailability or bioequivalence studies conducted on the same formulations of the drug product submitted for ANDA approval.
The FDA believes that data from any additional bioequivalence studies may be important in determination of whether a product is bioequivalent to the RLD, and aid in the evaluation of generic products.
FDA's Stance:
According to FDA these data will- Increase understanding of generic drug development and how changes in components, composition and methods of manufacture may affect formulation performance.
- Promote further development of science-based bioequivalence policies.
Format to be used for the Summary Report is the "Model Data Summary Tables" format consistent with the ICH Common Technical Document (CTD)available at the Office of Generic Drugs (OGD) web page.
Same Drug Product Formulation:
As per the amended regulation only data from bioequivalence studies of formulations considered same to the drug product submitted for ANDA approval need to be submitted.According to FDA same drug product formulation means, the formulation of the drug product submitted for approval and any formulations that have minor differences in composition or method of manufacture from the formulation submitted for approval, but are similar enough to be relevant to the FDA's determination of bioequivalence.
Formulations with differences in composition that are likely to result in a significant difference on formulation quality and performance, are considered non similar and studies need not be submitted.
Immediate Release Formulations and Extended Release Formulations:
Formulations of Immediate Release Formulations and Extended Release Formulations are considered similar if there is a difference in- Ingredient intended to affect the colour or flavour of the drug product
- Ingredient of the printing ink
- Technical grade and/or specification of an excipient
- Particle size or polymorphic form of the drug substance or excipients
- Individual excipient weight between the formulations compared but are Less than or equal to the percentages listed in below Table or cumulative total of all excipient weight differences is less than or equal to 10 percent
| Non-Release Controlling Excipient | % Difference in Excipient Weights Between Two Formulations* |
| Any Filler | 10 |
| Starch | 6 |
| Other | 2 |
| Any Binder | 3 / 1 ** |
| Calcium (Ca) or Magnesium (Mg) Stearate | 0.5 |
| Other | 2 |
| Talc | 2 |
| Other | 0.2 |
| Film Coat | 2 |
* Percentage of difference between another experimental formulation and the formulation proposed for marketing.
** 3 for Immediate Release and 1 for Extended Release formulations.
Formulations of Immediate Release Formulations and Extended Release Formulations are not considered similar if there is a difference in
- Addition or deletion of an excipient
- Individual excipient that exceeds the percentages shown in table above or the cumulative total of all excipient weight differences exceeds 10 percent.
Semisolid Dosage Forms:
Formulations of semisolid dosage form products are considered same if- The difference in the amount of an individual excipient is less than or equal to 5 or if the cumulative total of differences in the amount of all excipients is less than or equal to 7 percent.
- Formulations with differences in particle size distribution of the drug substance
A copy of the guidelines for your reference can be found at Submission of Summary Bioequivalence Data for ANDAs draft Guidance.
Read More
0
comments
Documents to be submitted to DCGI for grant of BE NOC
The documents required for DCGI No Objection Certificate (DCGI BE NOC) for conducting a biostudy in India are general in nature, however depending on the nature of the drug,disease and studies further specific information may also be required to be furnished by the firm
CDSCO has come up with a publication which details on the documents required for DCGI No Objection Certificate (DCGI BE NOC) for conducting a Bioequivalence study in India. All requirements are general in nature, however depending on the nature of the drug, disease and studies further specific information may also be required to be furnished by the firm.
I. New Drugs approved within period of more than 1 year & less than 4 years:
- For New Drugs approved within period of more than 1 year & less than 4 below specified documents should be submitted.
- The treasury challan will cost Rs. 15000/.
- Application in Form-44 duly signed, by the competent authority with name and designation.
- Undertaking by the Principal Investigator (PI) as per appendix VII of schedule "Y" of Drugs and Cosmetic Rules.
- A copy of the approval of the BE study centre from CDSCO.
- Sponsor's Authorization letter duly signed on their letterhead by the competent authority.
- study protocols.
- Complete Certificate of Analysis of same batches (both test & reference formulations) to be used in the BE study.
- In the case of multiple dose BE study adequate supporting safety data should be submitted.
- In the case of Injectable preparation the sub-acute toxicity should be submitted on the product of the sponsor, generated in two species for adequate duration.
- Depending on the nature of the drug like cytoxic agent, hormonal preparations etc. Proper justification for conducting studies on healthy volunteers/patients or male/female should be submitted.
- For New Drugs approved in India within period of 1 year below specified documents in addition to that specified in Section I, should be submitted.
- The treasury challan will cost Rs. 25000/.
- Clinical study data and published report of pharmacokinetic and pharmacodynamic study carried out in healthy volunteers data published in reputed journals.
- Package literature on the international product.
- For New molecule not approved in India but approved in the other countries below specified documents in addition to that specified in Section I & II, should be submitted.
- The treasury challan will cost Rs. 25000/.
- The study synopsis.
- Pre-clinical single dose data and repeated dose toxicity data.
- Regulatory status of the drug.
- Names of the countries where the drug is currently being marketed (to be mentioned in the covering letter also.
Read More
0
comments
