Biowaivers

DADA has supervised or monitored more than 100 complete BA/BE projects and has evaluated many more bioequivalence studies conducted by other companies. Thus DADA has acquired a vast body of knowledge about this very specific subject. DADA has demonstrated that it is not only able to adequately monitor bioequivalence studies; it is also able to find creative solutions for non-standard problem situations.

Besides monitoring studies, DADA has also supported many companies when bioequivalence studies produced suboptimal or unexpected results. By creatively re-evaluating all available data, it was often possible to explain deviating test results and to provide satisfactory answers to questions raised by the regulatory authorities. This has resulted in a number of publications in peer reviewed scientific literature, confirming the state-of-the-art quality of services rendered by DADA.

When bioequivalence studies fail to show equivalence of the test and reference drugs, it does not necessarily mean that the drugs are non-equivalent or that the study cannot be used. DADA has both in-house and external experts that can review the study data and determine the reasons for non-equivalence. Based on their analysis these experts can recommend further actions needed, whether it is returning to the formulation development, using different statistical methods for analysis of study data or anything in-between. For example, DADA has been the driving force behind the first generic registration of mesalazine tablets in Europe by successfully demonstrating that the current bioequivalence guidelines do not apply to this particular medicinal product. This resulted in a number of European marketing authorisations for our client, although the results of the bioequivalence study performed were out of standard specification.

The Guideline on the Investigation of Bioequivalence (CPMP/EWP/QWP/1401/98 Rev. 1/ Corr **) provides criteria for when a drug or drug strength does not need to undergo a bioequivalence study. These requirements are extensive, and DADA has experts capable of evaluating your product and writing a biowaiver where applicable.

DADA experts can evaluate old bioequivalence study reports that may need to be resubmitted for regulatory review (e.g. for new applicants or additional countries). Our experts have prepared numerous justifications for lack of Incurred Sample Reanalyses (ISR). The requirement to perform ISR has been introduced with the Guideline on bioanalytical method validation (EMEA/CHMP/EWP/192217/2009), which came into force on 1 February 2012.