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Core Registration Studies

Those primary safety and efficacy studies that the relevant government health agency uses to decide whether or not to approve the investigational drug or new use of a marketed drug. These studies are usually phase 3, always well controlled, randomized, of adequate size and, whenever possible, double blind. May also be called Pivotal or Confirmatory Trials.

Bioavailability and Bioequivalence
  1. What are the guidelines to be followed for bioequivalance studies? Are they following GCP guidelines?
    Yes. The definition of clinical trials in GCP guidelines includes pharmacokinetic studies.The European Guidelines demand that the report of a bioavailability or bioequivalence study should give the complete documentation of its protocol, conduct and evaluation complying with GCP-rules. Similarly, FDA’s GCP Bioresearch Monitoring Program inspections include bio-equivalence facilities.
    The ICH-GCP guidelines cover pharmacokinetic studies under the definition of clinical trial.
    ICH-GCP 1.12 Clinical Trial/ Study: Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/ or other pharmacodynamic effects of an investigational product(s), and/ or to identify any adverse reactions to an investigational product(s), and/ or to study absorption, distribution, metabolism, and excretion of an investigational product(s) with the object of ascertaining its safety and/ or efficacy.
    As bioequivalence studies are pharmacokinetic studies, they have to follow the same GCP guidelines as the clinical trials. In case a contract research organisation carries out a BE study, it assumes the role of the sponsor and the medical and non-medical personnel serving as the investigators have to assume the responsibilities of the investigator. As the quality assurance person does source data verification against raw data, he/ she also assumes the role of the monitor. All these personnel and their subordinate staff must be aware of the GCP guidelines and follow the GCP guidelines relevant to their functions.
  2. In bio-equivalence study, if a investigator was changed during the study, is it required to get an EC approval to continue the study?
    The PI is a signatory to the protocol and the person responsible for conduct of the study and the person who obtains EC approval for the study. The EC approves the protocol after considering qualifications of the investigator and other important documents. The EC has to know whether the qualifications of the new PI are similar to previous PI and whether he/she would be able to conduct the study as per approved protocol. According to ICH-GCP (3.3.7 and 4.5.2) only the change(s) which involve logistical or administrative aspects of the trial (e.g., change of monitor(s), telephone number(s)) do not need prior approval of EC. The change of PI is a major change. This is an amendment that requires approval from the EC Q 2.
  3. In a BA/BE study, is it required to have an impartial witness sign on the informed consent? If a person is already gave witness to some other subject in that study is he considered as witness to another subject in the same study?
    No. An impartial witness is required only if the subject is illiterate and his legal representative is illiterate. As per ICH-GCP definition an impartial witness is a person, who is independent of the trial, who cannot be unfairly influenced by people involved with the trial.
    As the other study subject is involved in the study, he can be influenced by the study team. Hence, he cannot become an impartial witness.
  4. Why don’t we carry the BA/BE studies in patients rather than healthy volunteers?                                                                                                                       BA/BE is a comparison of 2 generics. When we use volunteers, they have healthy body systems. Hence, the differences between the 2 formulations are due to pharmaceutical differences and not differences in the functions of different body systems e.g. liver and kidney. If we use patients, their organs are not healthy and this may affect the pharmacokinetic processes. Hence, the BA/BE will be influenced by the disturbances in the patient’s body functions. However, during the drug development, when you need information about effect of disturbed body functions e.g. effect of abnormal liver function on BA, the studies are done in patients.
  5. It is acceptable if we conduct BA/BE studies and phase 1 clinical trial at the same facility?
    However, as the objectives of the phase I and BA/BE are different, most companies keep the clinical beds separate. The focus of phase I is safety. Hence, the clinic requires special cardiac monitors for each volunteers and competent and adequate medical staff to look after volunteer safety. In case of BA/BE, the objective focuses on timed blood collections for PK study. Hence, the there are no special equipments required. Most CROs keep separate clinics for Phase I and BA/BE study. These types of arrangements are critical to assure the auditors and regulatory inspectors about human volunteer safety and protection.
  6. Is there any difference between protocol & CRF of the BA/BE study & regular clinical study for a new molecule?
    The principles of protocol are same for Clinical Trial and BA/BE.
  7. In BA/BE studies is it necessary for an investigator and sub-investigator to undergone GCP training?
    GCP training is a must for the whole team. Relevant sections of ICH are cited below:
    2.8 Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective task(s).
    ICH 4.1.3 The investigator should be aware of, and should comply with, GCP and the applicable regulatory requirements
    4.2.4 The investigator should ensure that all persons assisting with the trial are adequately informed about the protocol, the investigational product(s), and their trial-related duties and functions.

Opinion Poll

Which organizations listed below would you say has the greatest responsibility in educating the public about clinical trials?
This opinion poll provides an informal way for the clinical research community to express its views on current topics. The results are not a scientific poll and do not necessarily reflect the percentages of all clinical researchers who agree with these positions.