Do we conduct BA/BE studies in case of generic vaccines?
Manoj Sharma

As per the Drugs Cosmetics Act 122E Definition of new drug, all vaccines are considered new drugs. Hence, it is necessary to conduct clinical trials with any vaccine prior to registration.

Indian GCP guidelines in section 7 cover the vaccine trials.
7.1 Clinical Trials of Vaccines
7.1.1 Phases of Vaccine Trials

The guidelines to conduct the clinical trial on investigational vaccines are similar to those governing a clinical trial. The phase of these trials differs from drug trials as given below:

Phase I: This refers to the first introduction of a vaccine into a human population for determination of its safety and biological effects including immunogenicity. This phase includes study of dose and route of administration and should involve low risk subjects.

Phase II: This refers to the initial trials examining effectiveness (immunogenicity) in a limited number of volunteers. Vaccines can be prophylactic and therapeutic in nature. While prophylactic vaccines are given to normal subjects, therapeutic or curative vaccines may be given to patients suffering from particular disease.

Phase III: This focuses on assessments of safety and effectiveness in the prevention of disease, involving controlled study on a larger number of volunteers (in thousands).

Can a sponsor be present for project specific training that is provided to the patient for use of study drug? If the investigator staff is unable to train them properly, can the sponsor train the patient?
Meghana Abhayankar
There is no guideline on this situation, which is essentially related to confidentiality of the patient's identity. . In Phase I or bioavailability monitoring, the sponsor's monitor is present when the study is taking place. However, the monitor's role in this situation is restricted to monitoring responsibilities without violating the confidentiality of the subject. The monitor cannot provide any training to the subjects.

Pl see the following ICH GCP statement.
ICH GCP 4.8.10 (n) That the monitor(s), the auditor(s), the IRB/IEC, and the regulatory authority(ies) will be granted direct access to the subject's original medical records for verification of clinical trial procedures and/or data, without violating the confidentiality of the subject, to the extent permitted by the applicable laws and regulations and that, by signing a written informed consent form, the subject or the subject's legally acceptable representative is authorizing such access.

In all other situations, the sponsor or his/her representative cannot meet the patients for any purpose including training. I am aware of cases where a sponsor approached an ethics committee (EC) with such request and EC did not give permission for the sponsor to interact with the patients. The major issue of concern is confidentiality of subject's identity. The sponsor's knowledge of a patient's identity can be misused for commercial purpose.

Why Phase I studies are not conducted on healthy adult human female volunteers?
Manoj Sharma
Usually, the toxicity documentation prior to Phase I does not include reproductive toxicity data. Hence, female subjects with child bearing potential are not included in Phase I.

I have one query regarding safety reporting regulatory requirements. Do Foreign SAEs (not SUSARs) should be reported to DCGI? What is regulatory requirement for SUSAR / CIOMs reporting?
Vrunda Pandya

● As per Schedule Y 2005, only Indian unexpected SAE (related and unrelated) are to be reported to DCGI.
● For international SAEs, we need to submit only SUSARs.
● ICH E2A recommends that all adverse drug reactions (ADRs) that are both serious and unexpected (SUSAR) are subject to expedited reporting
● Indian GCP 1.11. Adverse Drug Reaction Reporting: The Sponsor should expedite the reporting to all concerned (including the Ethics Committee and the regulatory authorities) of all serious and/or unexpected adverse drug reactions.

What is a non-therapeutic trial?
Kavita Nainani
In a non-therapeutic trial, a subject does not get any potential benefits of therapy. Phase I in healthy volunteers is an example.