Meeting Regulatory Requirements for Drugs with a Narrow Therapeutic Index: Bioequivalence Studies of Generic Once-Daily Tacrolimus

• Main Authors: Gantar K, Škerget K, Mochkin I, Bajc A
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-09-01
• Series: Drug, Healthcare and Patient Safety
• Subjects: tacrolimus; bioequivalence; narrow therapeutic index; once-daily; generic
• Online Access: https://www.dovepress.com/meeting-regulatory-requirements-for-drugs-with-a-narrow-therapeutic-in-peer-reviewed-article-DHPS

Kaja Gantar,1 Katja Škerget,1 Ilya Mochkin,2 Aleksander Bajc1 1Sandoz Development Center Slovenia, Lek Pharmaceuticals d.d, Ljubljana 1526, Slovenia; 2Sandoz International GmbH, Holzkirchen 83607, GermanyCorrespondence: Ilya MochkinSandoz International GmbH, Industriestraße 18, Holzkirchen 83607, GermanyEmail [e-mail]: Despite growing clinical confidence in generics and their potential to reduce long-term healthcare costs, the transplant community have had real concerns about the use of generic immunosuppressants. One such immunosuppressant is tacrolimus, a cornerstone of lifelong treatment for patients who have undergone a solid organ transplant. Tacrolimus has a narrow therapeutic index (NTI), giving rise to questions about the potential for clinically relevant altered drug exposure. Its use in transplant patients also gives rise to questions about the most discriminative subject population for bioequivalence studies. The recognised need for stringent criteria to support approval of generic drugs with an NTI led the European Medicines Association and Health Canada to provide detailed information on requirements for bioequivalence studies and introduce tighter bioequivalence limits for these drugs, including tacrolimus. The aim of this article is to illustrate how regulatory guidance is implemented during the clinical development of generic immunosuppressants, using a generic, once-daily prolonged-release formulation of tacrolimus as an example.Keywords: tacrolimus, bioequivalence, narrow therapeutic index, once-daily, generic