Bio-waiver Studies are conducted at DRC in accordance with the MOH & International guidelines for comparative dissolution profiles studies.
Institutional Review Board (IRB)
The study was conducted in accordance with the MOH & international guidelines for in vitro, as well as with the latest guidelines on Good Laboratory Practice (International Conference on Harmonization) in so far as they do not intervene with the Egyptian guidelines. The standard operating procedures of the Pharmaceutical Research Unit will be provided upon request.
In accordance with Egyptian legislation the following was required before the study is initiated:
· Approval of the protocol by DRC and the sponsor
· Approval of the protocol by the Institutional Review Board.
Introduction:
Objective:
Comparative Dissolution study (Bio-Waiver Study) of TEST PRODUCT Versus REFERENCE PRODUCT.
Guidelines for carrying out Bio-Waiver studies
A. Investigator qualification and Agreements:
The investigator should be qualified by education, training and experience to assume responsibility for the proper conduct to the trial, and should meet all the qualifications specified by the applicable regulatory requirements, and provide an evidence of such qualifications through up-to-date curriculum vita and/or other relevant documentations requested by the sponsor or the regulatory authorities.
Investigator should be aware of, and should comply with good laboratory practice (GLP) and the applicable regulatory requirements, also to keep a number of qualified staff to conduct the procedural examinations properly and safety. There should be a written agreement between the investigator and the sponsor before the commencement of the study. The investigator/institution should permit monitoring and auditing by the sponsor to the information regarding the current status of the work.
B.Protocol:
Investigator is responsible for ensuring that an investigation is conducted in accordance with the signed investigator (approved protocol) and applicable regulations.
1. Selection of investigators
Each investigator should have appropriate expertise, qualifications and competence to undertake the proposed study. Prior to the study, the investigator(s) and the sponsor should establish an agreement on the protocol, the monitoring, the auditing standard operating procedures (SOP) and the allocation of study-related responsibilities.
2.Study Design
a.Weight Variation,content uniformity and potency determnination.
b. Stage (I):
(i) Identification:
Identification testing on the test and reference product lots should be performed as described in the official compendia.
(ii) Comparative Dissolution Profile:
In vitro dissolution testing done on test and reference products in 3 different pH media as described in the official compendia.
c. Stage (II):
Validation of Analytical Method:
The analytical methods used in bioavailability/bioequivalence studies must be well characterized, validated and fully documented. It must be performed before-study and within study validation.
Major validation and Stability steps required are:
1. Accuracy.
2. Precision between days (Intraday reproducibility).
3. Precision between days (Intraday repeatability).
4. Limits of quantitation (if appropriate).
5. Linearity.
6. Recovery.
7. Stability
d. Stage (III):
Presentation of Data
Weight Variation, Potency, and content uniformity results are presented in tabulated form for each individual dosage form, average percentage of active substances, S.D.& C.V.%.
For each Dosage form of test and reference products, percentage amount dissoluted at every sampling interval is presented in a tabulated form and average percent dissolution at each sampling interval, S.D.& C.V.%. Similarity factor and statistical analysis of variance are determined.
Reserve of samples:
The investigator should retain an appropriately identified reserve sample of the test and reference products for a period of 3-5 years.