Pharmaceutical Clinical Bioequivalence Study (BA/BE) Course

Good clinical practice (GCP) is an international ethical and scientific quality standard for designing, recording and reporting trials that involve the participation of human subjects. ... This is a statement of ethical principles developed by the World Medical Association.

GCP - 13 Principles

1. Ethics Clinical trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with GCP and the applicable regulatory requirement(s).

2. Trial risk vs trial benefit Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risks.

3. Trial participants The rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society.

4. Information on the Medicinal Product The available non-clinical and clinical information on an Investigational Product should be adequate to support the proposed clinical trial.

5. Good quality trials Clinical trials should be scientifically sound, and described in a clear, detailed protocol.

6. Compliance with the study protocol A trial should be conducted in compliance with the protocol that has received prior institutional review board (IRB)/independent ethics committee (IEC) approval/favourable opinion.

7. Medical decisions The medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician or, when appropriate, of a qualified dentist.

8. Trial staff Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective task(s).

9. Informed consent Freely given informed consent should be obtained from every subject prior to clinical trial participation.

10. Clinical trial data All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation and verification.

11. Confidentiality The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).

12. Good Manufacturing Practice Investigational products should be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP). They should be used in accordance with the approved protocol.

13. Quality assurance Systems with procedures that assure the quality of every aspect of the trial should be implemented.

Criteria for BE study population:

• Min. of 12 subjects

• 18 years of age/ older (18-55)

• capable of give informed consent

• Healthy volunteers ~ less PK variability

• Use Patients when safety concerns preclude healthy volunteers

• Non smoker

• No alcohol & drug abuse history

  
  

• Male & Female

1. Female shouldn’t get pregnant at beginning /durning the study

2. Females only ~ contraceptives

3. Males only ~ Teratogens

• BMI within 18.5 and 30 kg/m2

• Review of medical history.

• History of liver, kidney, hematological functions

• Test for alcohol & drug abuse to be done

• An ECG to be done if there is a chance of cause

• Phenotyping / genotyping of subjects may be considered for safety / PK reasons.

• In parallel design~ the treatment groups should be comparable (age, weight, sex, ethnic, smoking, metabolic status)

• If the drug product is predominantly intended to use in elderly-> applicant should include as many subjects as possible at /above age 60 / provide justification if no subject at/above 60 is included in study

• Adult BE study data can be used to support BE assessment in pediatric patients. But if a drug is predominantly used in child < 6yrs, provide justification that adult BE study data is relevant to pediatric patients

• Justification should include inactive ingredients that they are safe for pediatric use

• Special population > If there is a significant difference in dissolution between test and reference products under a certain condition > drug limited to a specific population

• Achlorhydric subjects > If there is a significant difference in dissolution between test and reference products at pH 6.8

• Healthy adult subjects > If there is no significant difference in dissolution between test and reference products at pH 6.8

Within GCP, studies must be reviewed and receive approval/ favourable opinion from an Independent Ethics Committee (IEC)/ Institutional Review Board (IRB) prior to enrollment of study subjects. The investigator generally assumes responsibility for obtaining IEC/ IRB review of the study protocol. Copies of any approval/favourable opinion are then provided to the sponsor.

Enrollment of subjects into the study:

recruitment, eligibility, and informed consent The clinical investigator has primary responsibility for recruiting subjects, ensuring that only eligible subjects are enrolled in the study, and obtaining and documenting the informed consent of each subject. Within GCP, informed consent must be obtained from each study subject prior to enrollment in the study or performing any specifi c study procedures