Logo Annals of Transplantation Logo Annals of Transplantation Logo Annals of Transplantation

21 May 2009

Generic products of immunosuppressive drugs according to incoming new emea guideline

P Kunicki

Ann Transplant 2009; 14(1): 75-76 :: ID: 880478


Note for Guidance on the Investigation of Bioavailability and Bioequivalence,
CPMP/EWP/QWP/1401/98, EMEA, 26 July 2001, presents general rules for
generic drugs registration. For majority of generally acting drugs - simple
single-dose, 2-period, 2-sequence, crossover bioequivalence study in young
healthy volunteers in fasting state is usually performed. The decision regarding bioequivalence is based on 90% confidence intervals for AUC and Cmax ratios (test/reference) being within 80-125% for log-transformed data. For many years, such approach was criticized as inappropriate for some drugs with narrow therapeutic range, also called as "critical dose drugs". As a result of scientific debate, a new EMEA Guideline on the Investigation of Bioequivalence is coming into operation in 2009. The class of narrow therapeutic index drugs (NTDIs) is formally created for agents with steep concentration response relationship for efficacy and/or toxicity. These drugs require dosage individualisation based on therapeutic drug monitoring or titrated according to clinical response as a high risk of serious clinical consequences is expected in the event of too low or too high concentrations. All primary immunosuppressive drugs (cyclosporine, tacrolimus, sirolimus, and everolimus) can be easily and undoubtedly considered as NTDIs. However, the classification as NTDI must be made individually for particular drug. In these specific cases, the acceptance interval for AUC and Cmax ratios may need to be tightened to 90-111%. Moreover, in individual cases additional or alternative requirements might be set. Described standards oblige Registration Agencies to obey more restrictive rules for generic products of immunosuppressive drugs.



In Press

06 May 2022 : Original article  

Phosphatidylethanol (PEth) for Monitoring Sobriety in Liver Transplant Candidates: Preliminary Results of D...

Ann Transplant In Press; DOI: 10.12659/AOT.936293  

27 Apr 2022 : Review article  

A Systematic Review of the Literature on Chronic Kidney Disease Following Liver Transplantation

Ann Transplant In Press; DOI: 10.12659/AOT.935170  

Most Viewed Current Articles

29 Dec 2021 : Original article  

Efficacy and Safety of Tacrolimus-Based Maintenance Regimens in De Novo Kidney Transplant Recipients: A Sys...

DOI :10.12659/AOT.933588

Ann Transplant 2021; 26:e933588

26 Jan 2022 : Review article  

Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Risk Factors and Predictive Models

DOI :10.12659/AOT.934924

Ann Transplant 2022; 27:e934924

24 Jul 2020 : Review article  

Kidney Transplantation in the Times of COVID-19 – A Literature Review

DOI :10.12659/AOT.925755

Ann Transplant 2020; 25:e925755

15 Mar 2022 : Case report  

Combined Liver, Pancreas-Duodenum, and Kidney Transplantation for Patients with Hepatitis B Cirrhosis, Urem...

DOI :10.12659/AOT.935860

Ann Transplant 2022; 27:e935860

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358