BioPharm

10 BioPharm International eBook October 2018 www.biopharminternational.com A s a r e s u l t , d e m a n d h a s increased for chromatography and mass spectrometry technology pro- viders to design instrumentation, software informatics, and work- flows to support protein analysis studies. In addition, these analyti- cal tools are required to be more accessible and automated to con- duct acquisition, processing, and reporting from characterization and comparability studies that are needed for innovator and biosimi- lar approvals (2). BioPharm International spoke to Patricia Hurley, PhD, senior direc- tor, Regulatory Consulting; and Duu-Gong Wu, PhD, senior direc- tor, CMC/Regulatory Consulting, both with PPD Consulting; and Edward Tabler, associate director, PPD Laboratories' bioanalytical lab, to gain insight into the impact that analytical testing on biosimilars has on their pathway to regulatory approval. ANALYTICAL ASSURANCE B i o P h a r m : I n b i o s i m i l a r d r u g development, long-term efficacy and safet y are largely based on clinical studies that have already been done on the reference bio- logic, but are these studies alone considered suff icient to ensure that a biosimilar can comparably replace the reference product? H u r l ey (PPD Co n s u l t i n g): L ong- term safety and efficacy of a bio- similar cannot be based on past clinical st ud ies w ith the refer- ence produc t alone, but rather on abbreviated data that include comparative clinical studies fol- lowing the demonstration of ana- lytical similarity (comparability). It is also important to note that a biosimilar is not regarded as a generic of a biologic. That is due to t he nat u ra l va r iabi l it y a nd inherent complexity in manufac- turing of biologics for which the demonstration of identical quality attributes (pharmaceutical equiva- lence) as required by the authori- ties is extremely difficult, if not impossible. The major regulatory authorities have issued guidance documents that clearly outline the expectations for developing a biosimilar. They emphasize that a step-wise approach should be taken to demonstrate there are no clinically meaningful differences between the biosimilar and the reference product. The o u t l i n e d s t e p - w i s e a p p r o a c h involves a detailed evaluation of the proposed biosimilar product against the approved reference produc t, f i rst w it h respec t to e x t e n s i v e C M C [ c h e m i s t r y, ma nu fac t u r i ng , a nd cont rol s] characteristics, then by relevant nonc l i n ic a l p e r for ma nce, a nd finally by clinical phamacokinetic/ safet y/immunogenicit y/eff icac y parameters in an appropriate and sensitive population. Any proposed deviations from the issued guidance would be expected to be thoroughly justified and discussed through appropriately planned regulatory a g e n c y i n t e r a c t i o n s a t k e y milestones throughout a sponsor's development program. GUIDING PRINCIPLES BioPharm: What f urther analyti- cal st udies would be needed to ensure biosimilarity to the refer- ence product? Wu (PPD Consulting): The major regulatory agencies, such as FDA a n d t h e E u r o p e a n M e d i c i n e s A g e n c y ( E M A ) , h a v e i s s u e d d e t a i le d g u id a nc e d o c u me nt s that prov ide g uiding principles on how analy tical tests should be performed to assess the ana- lytical similarity or comparabil- ity between a reference product and a proposed biosimilar. These tests must be able to compare the physicochemical and biological characteristics of the two prod- ucts, in some cases down to the f i nge r pr i nt le ve l. Sp e c i f ic a l ly, these tests are designed to cover t h e p r i m a r y, s e c o n d a r y, a n d h ig he r orde r of prote i n st r uc- tures; the purity and impurities; the post-translational modifica- tion, such as glycan profiles; the potency or biological activities; and other functional tests, such as receptor binding. Analytical similarity by itself is not designed to 'ensure' biosimi- larity, but is a first step in the step- wise approach to the development of biosimilars. The comparability/ similarity of the quality attributes Biopharma Laboratory Best Practices Biosimilar Analysis Demand has increased for providers to design instrumentation, software informatics, and workflows to support protein analysis studies. Analytical chemists are increasingly challenged to develop routine and automated characterization workflows for innovator and biosimilar biologics.

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