Product related impurities are identified and characterized during product development stage, and it is assessed based on the product critical quality attributes (CQA). CQA is defined as a physical, chemical, biological or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality (ICH Q8 R2). They are identified through a science based systematic risk assessment with combination of clinical and non-clinical knowledge, reputable publications, similar existing biological products, and general pharmaceutical requirements. CQA need to be assessed for their potential variability within the manufacturing process, risk ranking and filtering (RRF) of quality attributes (QA), and their impact on biological activity, pharmacokinetics (PK) and or pharmacodynamics (PD), immunogenicity, and safety, in order to define a sound control strategy and acceptance criteria. Acceptance specifications can be set according to pharmacopeia requirements (USP, Ph Eur, JP and ChP).

Product quality attributes (QA) are categorized into 4 groups to rank CQA: (1) pharmaceutical attributes; (2) contaminants; (3) process-related impurities; (4) product-related variants and impurities. Examples of each group is listed in the following table and testing of CQA related parameters (e.g., CPP) will be conducted during manufacturing process and they should be kept within defined acceptance criteria.

Reference:

1. Brorson K, Phillips J. Defining your product profile and maintaining control over it, Part 4. BioProcess Int. 2005;3: 48–53.

2. Bukofzer S, Ayres J, et. al., Industry perspective on the medical risk of visible particles in injectable drug products. PDA J Pharm Sci Technol. 2015 Jan-Feb;69(1):123-39.