The effect of temperature on the stability of PCSK-9 monoclonal antibody: an experimental study

Abstract

Background PCSK9 monoclonal antibody lowers plasma PCSK9 and LDL-cholesterol levels. The manufacturers recommend drug storage at 2–8 °C, and not above 25 °C. This study aimed to investigate drug stability at various temperatures that this drug could be exposed to during medication handling and transportation in tropical countries. Methods Alirocumab and evolocumab were tested in 3 study conditions: room temperature (RT), cooler device with cold pack, and freeze-thaw for 9 and 18 h. Heated drugs were used as negative control. Free plasma PCSK9 levels from 9 hyperlipidemia subjects were measured with ELISA. Results Average subject age was 49.2 ± 18.4 years. Percent PCSK9 inhibition significantly declined in heated drugs compared to baseline. Average RT during the study period was 30.4 ±2.6 °C. Change in percent PCSK9 inhibition of PCSK9 mAb at RT from baseline was − 5.8 ± 4.4% (P = 0.005) and − 11.0 ± 8.9% (P = 0.006) for alirocumab at 9 h and 18 h, and − 9.7 ± 11.8% (P = 0.04) and − 15.1 ± 14.3% (P = 0.01) for evolocumab at 9 and 18 h, respectively. In contrast, there were no significant changes in percent PCSK9 inhibition from baseline when PCSK9 mAb was stored in a cooler. In freeze-thaw condition, changes in percent PCSK9 inhibition from baseline to 9 and 18 h were − 5.2 ± 2.9% (P = 0.001) and − 2.6 ± 4.9% (P = 0.16) for alirocumab, and − 1.8 ± 4.2% (P = 0.24) and 0.4 ± 6.1% (P = 0.83) for evolocumab. Conclusion Proper drug storage according to manufacturer’s recommendation is essential. Drug storage at RT in tropical climate for longer than 9 h significantly decreased drug efficacy; however, storage in a cooler device with cold pack for up to 18 h is safe.

Preserved SARS-CoV-2 neutralizing IgG activity of in-house manufactured COVID-19 convalescent plasma

“…Several studies investigated antibody activity or titer after freeze-thaw cycles, and most of the results described that antibody activity or titer were preserved after the freeze-thaw process [10] , [15] . Plasma antibodies against SARS-CoV-2 collected from convalescent participants were also evaluated after the freeze-thaw cycle, and the activities did not change significantly [16] .…”

Injection of an improperly stored proprotein convertase subtilisin/kexin type 9 monoclonal antibody in a patient with secondary dyslipidemia from nephrotic syndrome: a case report

“…Plasma PCSK9 levels were measured using a quantitative enzyme-linked immunosorbent assay (ELISA). The complete methodology of PCSK9 quantification has been described previously [5]. In brief, protein G Agarose and washing buffer were used to remove other immunoglobulin Gs from the serum sample and drug complex before an experiment.…”

“…Despite an emphasis on proper drug storage, unexpected errors during storage can occur. We previously reported a decrease in PCSK9 inhibitory activity of PCSK9 mAb stored in room temperature conditions in vitro [5]. However, the effect of injecting inappropriately stored drugs in humans has never been reported.…”

“…PCSK9 mAb is protein, and thus prone to a variety of degradation pathways, especially if stored in inappropriate temperatures or conditions [4,5]. Hence, manufacturers recommend keeping unopened drugs between 2 °C and 8 °C or at room temperature not exceeding 25 °C for a maximum of 30 days to get the best therapeutic effect.…”

Climate change and the prevention of cardiovascular disease

“…Certain medications are particularly heat-sensitive. For example, the efficacy of PCSK9-inhibitors significantly decreases when stored at temperatures higher than 25 °C for several hours [ 220 ], and insulin has long been recognized as a heat-sensitive medication that undergoes degradation at temperatures above 30 °C. With increasing temperature and temperature variability, those most disadvantaged will not have the resources to store their therapies correctly.…”