– Pharma Safety Solutions, LLC, Noblesville, IN, United States
Background: The safety and effectiveness profile of biologic products could be affected if changes in their manufacturing and purification processes ensued, which are often needed for insulin products.
Objectives: We describe a lot-specific pharmacovigilance program for insulin lispro following the introduction of a manufacturing change in the purification process in October 2013.
Methods: Side-by-side Proportional Reporting Ratio (PRR) disproportionality analyses were performed on the manufacturer-maintained database of adverse event reports for insulin lispro. Lot-level analyses included insulin lispro lots for reports submitted between October 2013-October 2018 (lots with new purification process); insulin lispro lots for reports between January 2008-October 2013 (historic); and lots for reports between October 2013-October 2018 (concurrent, including both old and new lots). MedDRA PT of interest included changes in insulin effect and hypersensitivity (including immunogenicity and injection site reactions). New lots compared to concurrent and historic lots separately. Concurrent lots compared to historic lots to minimize biases emerging from ripple-effect. Drug-event combinations with PRR≥2.0 are considered potential signals that warrant further review.
Results: A total of 35,075 reports for insulin lispro lots were compared to 11,302 reports for historic lots; 34,986 reports for new lots were compared to 32,737 reports for concurrent batches; and 32,737 reports for concurrent lots were compared to 11,302 reports for historic insulin lispro lots. Signal detection results were: lack of drug effect (new vs. historic, PRR=1.15; new vs. concurrent, PRR=1.14; concurrent vs. historic, PRR=1.01); increased drug effect (new vs. historic, PRR=1.11; new vs. concurrent, PRR=1.21; concurrent vs. historic, PRR=0.91); and hypersensitivity reactions (new vs. historic, PRR=0.85; new vs. concurrent, PRR=0.86; concurrent vs. historic, PRR=0.99).
Conclusions: No signal has been identified implicating a worsening of glycemic control or hypersensitivity in users of insulin lispro from lots developed using new purification process. Lot-level pharmacovigilance provides an objective assessment of biological product comparability before and after changes in the manufacturing process.
