OUTSOURCING CONSIDERATIONS
Outsourcing Biologics Stability Programs: Points to Consider
Jon S. Kauff man, PhD
Senior Director, Biopharmaceutical Services Eurofi ns Lancaster Laboratories
Submitted: 08/28/2014 Accepted for Publication: 09/02/2014
As the pipeline of biologics continues to grow, biopharmaceutical organizations are outsourcing an increasing number of stability studies. Careful consideration must be given when choosing a partner for these programs due to their inherent complexity. Several key points to consider, including capability, capacity, protocol development, and project management, are discussed here.
Background
According to ICH Q1A (R2), “The purpose of stability testing is to provide evidence on how the quality of a drug substance or drug product varies with time under the influence of a variety of environmental factors such as temperature, humidity, and light, and to establish a re-test period for the drug substance or a shelf life for the drug product and recommended storage conditions.”1
In the case of biologics, ICH Q5C states, “The evaluation of stability may
Dr. Jon S. Kauff man is Sr. Director of Biochemistry, Method Development & Validation and Protocol
Development and Technical Writing at Lancaster Laboratories. His teams are responsible for developing and validating
methods and performing analysis of clinical and commercial samples for stability and release
purposes. This includes methods for the testing of residual impurities in biopharmaceutical
products and in-process samples. Dr. Kauff man’s departments also perform mass spectrometric characterization and leachable and extractable studies. Dr. Kauff man’s key roles are to interface with clients and his team to ensure positive
project outcomes by maintaining compliance and a high level of quality; meeting milestones and
delivery requirements; and fi nding cost-eff ective, value-added solutions. He earned a doctorate in chemistry from the University of Delaware and has over 25 years of experience in the analytical testing fi eld.
necessitate complex analytical methodologies. Assays for biological activity, where applicable, should be part of the pivotal stability studies. Appropriate physicochemical, biochemical, and immunochemical methods for the analysis of the molecular entity and the quantitative detection of degradation products should also be part of the stability program whenever purity and molecular characteristics of the product permit use of these methodologies.”2
ICH provides specific guidance for biologics for several reasons. When compared to typical small molecule products, proteins exhibit greater instability, are more sensitive to the environment, and require more complex analytical methodologies to fully characterize them. Some of the most common types of instability are shown in Table 1.
In addition, biological activity is highly dependent on interactions (both non-covalent and covalent), and biologics are particularly sensitive to environmental factors, such as temperature, light, oxidation, shear, and ionic content. Therefore, strict storage, packaging, handling, and transport conditions are usually necessary.
Table 1. Type Oxidation
Deamidation Denaturation Aggregation Hydrolysis
5 American Pharmaceutical Review | Biopharmaceutical Supplement 2014 Examples of Aff ected Moiety
Methionine, histidine, cysteine, tyrosine, tryptophan residues Asparagine and glutamine side chain amides Breakdown of three-dimensional structure Association of monomer units Sialic acid residues in glycoproteins
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