According to the FDA rules and regulations, all new drugs need proof that they are safe, tolerable and effective before they can be approved for marketing. The FDA also developed and issued explicit guidelines for a generic product's bioequivalency and stability, ensuring that products retain potency. The main rule is: if a drug product contains a drug substance that is chemically identical and is delivered to the site of action at the same rate and extent as another drug product then it is equivalent and can be substituted (switchable) for that drug product. Methods used to define bioequivalence as stated by the rule (FDA 21 CFR 320, 24) are: 1) Pharmacokinetic (PK) Studies in healthy volunteers, 2) and Comparative clinical trials .We have evaluated the switchability of Immunocell) Benta s.al, Beirut Lebanon) with Cellcept (Roche Switzerland using all of the above FDA rules. 1) PK; In a Single oral dose comparative, bioavailability study and in a multicenter clinical study. The study was performed according to the Helsinki accord of medical ethics and monitored by the contract research organization (CRO) Transmedical s.a.l, which is EU audit for good clinical practice (GCP). In healthy volunteers the pharmacokinetics of Immunocell and Cellcept were determined with blood levels at: 0, 20, 40, 1, 1h:20 min, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 hours. The area under curve (AUC), AUC extrapolated to infinity (AUC0-inf), rate of absorption (Tmax), extent of absorption (Cmax), half time (T1/2) of Immunocell and Cellcept were , (97.71166 – 103.95548) and (102.6642 – 108.3501) respectively, which are within the general 80-125 % FDA acceptance range; 2) Clinical trials: A comparative clinical trials in stable renal transplant patients: A multi-center study was performed at the American University of Beirut, St Therese Hospital, Sacre Coeur teaching hospital and Riyak teaching hospital. The patients were switched on 1:1 basis with no change in the dose of the additional immunosuppressive therapy that the patients were receiving (Cyclosporine or Tacrolimus). The patients were monitored weekly for MPA levels, liver function tests and renal function. The study was coordinated by St Mary’s hospital London UK and monitored by the CRO Transmedical s.al. Lebanon. In this study the blood trough levels for Cellcept and Imunocell were 1.68 ng/ml and 1.99 ng/ml respectively. The Cmax was 10.9 ng/ml and 12.14ng/ml for Cellcept and Imunocell respectively. There was no change on any of the laboratory parameters with the creatinine level at time of switch being 1.23 ng/ml and 1.21 ng/ml at 2 months post switch. The ratios of LSM and the 90 % confidence intervals for the In-transformed Parameters (AUC o-t, AUC inf, Tmax and Cmax) of Imunocell and Cellcept 500 mg tablets were 98 % & 95 % respectively which is within the 80-125 % FDA acceptance range. The Results from the, FDA required, studies for interchangeability (Bioavailability- Bioequivalence, Clinical Studies ) indicates that Imunocell and CellCept 500 mg tablets are switchable.
Volume : 6
Issue : 4
Pages : 65
St Mary’s Hospital, London, UK; American University of Beirut, Lebanon; and St Therese Hospital, Beirut, Lebanon