Antibody Forced Degradation Studies

When characterizing therapeutic proteins (including therapeutic monoclonal antibodies(mAbs)), it is important to consider the behavior of the material under any external stresses it may endure during production, shipment, storage, and patient delivery. Forced degradation refers to the intentional application of one or more stressors (e.g., high temperature, freeze-thaw, agitation, low pH, oxidation, photostability). At Creative Biolabs, we offer antibody forced degradation studies under a wide spectrum of forced stress conditions.

Importance of Forced Degradation Study

Forced degradation studies are an integral part of recombinant mAb therapeutics research and development throughout the life-cycle of the products for various purposes. Firstly, it can be used to evaluate the manufacturability of multiple candidates by assessing the propensity to degrade under relevant process, formulation, and storage conditions. Secondly, by identifying conditions such as buffers, excipients, pH, and temperature can help formulation development. Thirdly, the degraded samples can be used to test method parameters and also to establish stability-indicating methods at an early stage. Fourthly, by characterizing the degradation products, the major degradation pathways can be elucidated. Furthermore, in the comparability studies, differences that cannot be detected by release and extended characterization can become detectable under forced degradation conditions in a relatively short time period. Same degradation pathways and comparable degradation kinetics further ensure comparability.

Major Forced Degradation Conditions

• High temperature: High temperature can accelerate degradation pathways such as aggregation, fragmentation, and chemical modification. Proper high temperature can be selected by identifying the unfolding temperature measured through thermal stability techniques such as differential scanning calorimetry (DSC). Degradation under high-temperature stress can provide information for potential long-term degradation at the intended storage condition.
• Freeze-thaw: Freezing and thawing are stress to which mAb products are frequently exposed. The major degradation pathway during free-thaw is aggregation. It is often performed to determine the susceptibility of a mAb to temperature cycling.
• Agitation: mAbs encounter this physical stress during cell culture, purification, formulation, product filling, and shipping. The major degradation pathway caused by agitation (e.g., shaking and stirring) is the formation of aggregates. The susceptibility to agitation is commonly assessed to support the formulation and process development.
• Low and high pH: Low pH can cause aggregation and accelerate fragmentation. It is an important stress condition to evaluate because mAb purification processes typically involve exposure to acidic solution conditions. Similar to low pH, high pH conditions can lead to aggregation and fragmentation, making it important to evaluate for thorough process understanding and elucidation of degradation pathways.
• Photostability: It is a critical environmental factor that should be evaluated as defined in the ICH Q1B. The major degradation pathways due to light exposure include the formulation of aggregates, fragmentation, and oxidation.
• Oxidation: Forced oxidation is used to probe amino acid residues that are susceptible to oxidation and to understand if this oxidation affects antibody performance, e.g., binding affinity and potency.

At Creative Biolabs we can select from a full range of stress conditions and apply them specifically to the molecule of interest.

Typical Stress Conditions Provided by Creative Biolabs

• Intermediate and accelerated testing (ICH and non-ICH)
• Elevated temperature
• Freeze-thawing
• Freeze-freezing
• Various types of mechanical stress, e.g., shaking, stirring, etc.
• Photostability testing (ICH and non-ICH)
• pH stress (low and high pH)
• Forced oxidation
• Forced deamidation
• Shipment studies
• In-use stability studies
• Compatibility studies with various materials and the final administration conditions

Features of Our Services

• A wide range of analytical methods can be applied to monitor diverse degradation products
• Services can be tailored and optimized to meet different client requirements
• Services in accordance with ICH regulatory requirements

If you are interested in our service, please do not hesitate to contact us for more details.

Reference

1. Nowak, C. K.; et al. Forced degradation of recombinant monoclonal antibodies: A practical guide. MAbs. Taylor & Francis. 2017, 9(8): 1217-1230.

For Research Use Only.