TY  - JOUR
T1  - Manufacturing Drift Can Alter the Meaning of Comparability Without Creating a New Biologic
A1  - Mateo Alvarez
A1  - Sofia Herrera
A1  - Diego Cruz
A1  - Andres Castro
JF  - International Journal of Pharmaceutical Research and Allied Sciences
JO  - Int J Pharm Res Allied Sci
SN  - 2277-3657
Y1  - 2025
VL  - 14
IS  - 3
DO  - 10.51847/S5uoeG2KCD
SP  - 162
EP  - 172
N2  - Biological products are manufactured through evolving process histories rather than reproduced as chemically invariant objects. Improvements in cell culture, purification, analytical capability, formulation, scale, site, equipment, and control strategy can alter measured quality attributes even when the therapeutic entity remains clinically continuous. The central problem is therefore not whether a post-change product is analytically identical to its predecessor, but whether observed change alters the evidentiary meaning of comparability. This Current Opinion argues that manufacturing drift should be interpreted through linked but non-equivalent evidence layers: process state, product attribute, structure–function relationship, exposure or immunogenicity relevance, and clinical consequence. Analytical drift can be real without being functionally important; conversely, apparently modest changes can matter when they affect a critical structural feature or mechanism. Comparability should therefore be treated as a lifecycle judgement that can be strengthened, reopened, or escalated as new evidence appears. The article further separates manufacturing-change comparability from biosimilarity and interchangeability, which may use overlapping analytical tools but answer different provenance and regulatory questions. A proposed lifecycle framework is developed around residual uncertainty rather than a universal numerical threshold.
UR  - https://ijpras.com/article/manufacturing-drift-can-alter-the-meaning-of-comparability-without-creating-a-new-biologic-uzjjcmztgrcskkl
ER  -