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Interactions between Therapeutic Proteins and Acrylic Acid Leachable
Dengfeng Liu1, Yasser Nashed-Samuel, Pavel V Bondarenko
1Process & Product Development, Amgen Inc., Thousand Oaks, CA.
PDA Journal of Pharmaceutical Science and Technology
|February 7, 2012
Summary
Acrylic acid leachable from syringes can modify therapeutic proteins. This interaction, occurring at lysine, N-terminus, and histidine sites, may alter protein properties and pose toxicity risks.
Area of Science:
- Pharmaceutical Science
- Biochemistry
- Materials Science
Background:
- Leachables are compounds migrating from packaging into drug products.
- Acrylic acid was detected in syringes from Vendor X at approximately 5 μg/mL.
- Understanding leachable-protein interactions is crucial for biopharmaceutical safety.
Purpose of the Study:
- To investigate the interaction between acrylic acid leachable and a therapeutic protein (IgG2).
- To elucidate the reaction mechanism and identify modification sites on the protein.
- To assess the potential impact of acrylic acid modification on protein properties.
Main Methods:
- Incubation of IgG2 in sterilized Vendor X syringes at 45 °C for 45 days in pH 5 acetate buffer.
- Analysis of protein modification sites and reaction mechanisms.
- Evaluation of changes in protein properties due to modification.
Main Results:
- Acrylic acid was confirmed to migrate from Vendor X syringes into the IgG2 solution.
- Acrylic acid was found to modify the protein at lysine side chains, the N-terminus, and histidine side chains via Michael reaction.
- A small percentage (0.02%–0.3%) of protein was modified, potentially altering charge and hydrophobicity.
Conclusions:
- Direct interaction between acrylic acid leachable and a biopharmaceutical product was demonstrated.
- The reaction mechanism involving Michael addition to specific protein sites was proposed.
- Modified proteins may pose safety concerns due to acrylic acid toxicity and altered properties.
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