The exclusion of biological products (approved under the Public Health Service Act) from Title I of the Hatch-Waxman Amendments is being revisited today in the light of philosophical shifts in regulatory review, cost containment, and scientific consistency. The definition of drug versus biologic—be it scientific, legal, or administrative—is evolving and these overlapping working definitions further blur the regulatory distinction between drugs versus biologics. This is most clearly seen with the emergence of specified biotechnology products and the precedent of Center for Drug Evaluation and Research (CDER)-approved recombinant deoxyribonucleic acid (rDNA)-derived products under Section 505 of the Food Drug & Cosmetic (FD&C) Act. Improvements in production methods, process controls, and analytical test methods have given the Food and Drug Administration (FDA) the impetus for greater harmonization in regulatory review such as the Biologics License Application (BLA), which replaced the Product License Application (PLA) and Establishment License Application (ELA). Industry and regulators collaborated to create fast-track approvals and the ‘specified biotech’ paradigm to shed the long-standing “product = process” dogma. In doing so, entire classes of biotech-derived products are being brought to market faster, and significant manufacturing changes are being supported without repeating extensive Phase III clinical studies, and as some postulate—closer to the realm of multisource (or interchangeable products) competition by noninnovator companies. Though specified biotech and comparability protocols do not equal multisource biotech, there are many common conceptual elements, parallel tracks, and intersections that support cost savings and faster route to market for noninnovator manufacturers, especially with regards to demonstrating therapeutic equivalence. Though each situation is casedependent, what are some common features that could allow the same manufacturing changes under specified biotech as those supported for noninnovator multisource biotech pharmaceuticals? Given the range of complexity of moieties under the biotech umbrella, no single approach of demonstrating therapeutic equivalence would suffice for all. It should be evaluated first on a product class basis (eg, monoclonal antibodies, interferon, fibrinolytics, etc.) and then on a case-by-case basis using a tiered approach of combined analytical characterization + pharmacokinetic/pharmacodynamic (PK/PD) assessments + surrogate endpoint equivalence, if required. Assessment of immunogenicity, development