TY - JOUR
T1 - Nature and timing of post-approval manufacturing changes of tumour necrosis factor α inhibitor products
T2 - A 20-year follow-up study of originators and biosimilars
AU - Alsamil, Ali M
AU - Giezen, Thijs J
AU - Egberts, Toine C
AU - Doevendans, Erik
AU - Leufkens, Hubert G
AU - Gardarsdottir, Helga
N1 - Funding Information:
This study was funded by the Saudi Food and Drug Authority (SFDA) as a part of a Doctor of Philosophy (Ph.D.) project for AMA. The SFDA has no role in any aspect of the study, including the preparation, review, the approval of the manuscript, nor the decision to publish the manuscript.
Publisher Copyright:
© 2022
PY - 2022/8/1
Y1 - 2022/8/1
N2 - The manufacturing of biopharmaceuticals is complex, and minor changes in the process may affect quality attributes (QAs) that may, in turn, impact clinical outcomes. Regulatory documents from the European Medicines Agency were used to characterize two aspects, nature and timing, of post-approval MCs for originators and biosimilars TNF-α inhibitors that were on the European market up to May 2021. The nature of MCs was evaluated in two ways: (1) the type of MCs related to the drug substance (DS) or drug product (DP), classified as manufacturing, quality control, composition, packaging, or stability with various subtypes; and (2) the risk level according to the potential impact of the MCs on QAs, classified as low, medium, or high. Timing was defined as the date of the regulatory decision on the MC in relation to the approval date. We identified 801 post-approval MCs implemented to originators (mean: 137, range: 112-175) and biosimilars (mean: 30, range: 0-133). Most of implemented MCs for originators and biosimilars were classified as low and medium risk (88.1%), and a small fraction were considered high-risk (11.9%). The average incidence rates were comparable for both originators and biosimilars (7.0/year for MCs, 0.8/year for high-risk MCs). In 20% of MCs introduced to biosimilars, the DP manufacturing site was involved (9% for originators). In contrast, 16% of MCs introduced to originators were related to the DS manufacturing processes (only 7% for biosimilars). In conclusion, while the overall MC incidence rate and the risk level of MCs was not substantially different between TNF-α inhibitor products, we observed some differences in a few types of MCs related to DS manufacturing process and DP manufacturing site between originators and biosimilars. As far as our data shows there is no reasons to assume that post-approval MCs will lead to differences between TNF-α-i originators and biosimilars in clinical practice.
AB - The manufacturing of biopharmaceuticals is complex, and minor changes in the process may affect quality attributes (QAs) that may, in turn, impact clinical outcomes. Regulatory documents from the European Medicines Agency were used to characterize two aspects, nature and timing, of post-approval MCs for originators and biosimilars TNF-α inhibitors that were on the European market up to May 2021. The nature of MCs was evaluated in two ways: (1) the type of MCs related to the drug substance (DS) or drug product (DP), classified as manufacturing, quality control, composition, packaging, or stability with various subtypes; and (2) the risk level according to the potential impact of the MCs on QAs, classified as low, medium, or high. Timing was defined as the date of the regulatory decision on the MC in relation to the approval date. We identified 801 post-approval MCs implemented to originators (mean: 137, range: 112-175) and biosimilars (mean: 30, range: 0-133). Most of implemented MCs for originators and biosimilars were classified as low and medium risk (88.1%), and a small fraction were considered high-risk (11.9%). The average incidence rates were comparable for both originators and biosimilars (7.0/year for MCs, 0.8/year for high-risk MCs). In 20% of MCs introduced to biosimilars, the DP manufacturing site was involved (9% for originators). In contrast, 16% of MCs introduced to originators were related to the DS manufacturing processes (only 7% for biosimilars). In conclusion, while the overall MC incidence rate and the risk level of MCs was not substantially different between TNF-α inhibitor products, we observed some differences in a few types of MCs related to DS manufacturing process and DP manufacturing site between originators and biosimilars. As far as our data shows there is no reasons to assume that post-approval MCs will lead to differences between TNF-α-i originators and biosimilars in clinical practice.
KW - Biopharmaceuticals
KW - Biosimilars
KW - Comparability
KW - Consistency
KW - Manufacturing changes
KW - Originators
KW - Quality attributes
KW - Reference products
KW - Tumour necrosis factor alpha inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85131428840&partnerID=8YFLogxK
U2 - 10.1016/j.ejps.2022.106227
DO - 10.1016/j.ejps.2022.106227
M3 - Review article
C2 - 35636657
SN - 0928-0987
VL - 175
SP - 1
EP - 8
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
M1 - 106227
ER -