A total of 36 entries for mAbs were found published on the EMA website and 29 of these had publicly available EPAR reports. As of October 2014, these 29 EPAR reports contained details of 404 manufacturing changes authorized by the EMA. Of these, 22 were categorized as high-risk, 286 as moderate-risk and 96 as low-risk manufacturing changes The number of changes ranged from 0 (pertuzumab) to 50 (infliximab) with a median of 11 per product, and five products had in excess of 25 changes in manufacturing (infliximab, basiliximab, trastuzumab, adalimumab and eculizumab) . Since the elapsed time after authorization differs significantly (1998–2013) the annual number of manufacturing changes was introduced for comparison. The annual average number was 1.8 (range 0–3.71) .
Figure 2. Number of manufacturing changes for monoclonal antibodies in their European Public Assessment Reports according to risk category (during the search period all non-proprietary names relate only to the trade named medicines listed in.
Figure 3. Average number of manufacturing changes per product year elapsed since registration (during the search period all non-proprietary names relate only to the trade named medicines listed in.
Biological products vary over time as a result of modifications to the manufacturing process. Consequently, manufacturers need to demonstrate the consistency and robustness of the manufacturing process by implementing good manufacturing practices, modern quality control and assurance procedures, in-process controls and process validation Citation11. This applies to both originator products and biosimilars, and the manufacturing process for a biosimilar should be optimized to minimize differences between it and its reference protein. As noted in this short review, the regulatory authorities have extensive experience of assessing manufacturing changes over time and their impact on the efficacy and safety of the final product, for a wide range of mAbs. These same principles, using state-of-the-art science and technology, are being applied to biosimilar manufacturing and quality control.
The manufacturing change data presented herein indicate that, prior to the authorization of the first biosimilar mAb, the EMA had extensively evaluated the manufacturing process changes of originator mAbs, and gained significant experience in the change process and its impact on the safety and efficacy of biologicals. These comparability exercises became the guiding principles of biosimilarity to confirm no meaningful differences in quality, safety and efficacy. These exercises have been employed in biosimilar product development to ensure that sound scientific principles are adhered to. Since the manufacturing process for biosimilars will likely be different from the reference product for proprietary reasonsCitation1, physicians ought to be able to trust the expertise of regulatory authorities to confirm the similarity of previously approved originator products and their biosimilars akin to the pre- and post-manufacturing changes of original biologicals.
Manostaxx – Industrial Management Consulting
