Drug Product Critical Quality Attributes

Chamow & Associates continues our blog series detailing best practices for working with a contract development and manufacturing organization (CDMO). This series is intended to provide a potential sponsor company with sound advice in finding and choosing the right CDMO for its product development and managing that CDMO to perform to the company’s expectations.

Critical Quality Attributes (CQAs) are the benchmarks around which most quality-by-design implementations revolve. CQAs are part of the systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management (ICH Q8 R2).  Determined with the patient in mind, CQAs are tied to the Quality Target Product Profile (QTPP) which includes all product quality characteristics, and specifically, those critical attributes that ensure safety and efficacy defined in the product label (Target Product Profile).  Quality targets serve as the basis for process development activities and guide the selection of process steps, material attributes, equipment design and operation controls for the manufacturing process.

A CQA is a physical, chemical, biological, or microbiological property or characteristic that should be controlled within an appropriate limit, range, or distribution to ensure a desired product quality (ICH Q8 R2). ICH 6A further defines specifications as the set of criteria to which a drug substance or drug product should conform to be considered acceptable for its intended use. This term includes such attributes as identity, strength, purity and potency.

The approach to identifying CQAs begins with prospectively identifying all drug product quality attributes and creating the QTPP. The QTPP can be considered an expansion of the target, higher level, product profile. For example, the TPP will define the dosage form as IV, whereas the QTPP will include the attributes of concentration, color, and clarity. Next, all the quality attributes are evaluated for severity of harm (safety and efficacy) to a patient if that quality attribute is not met; not all quality attributes result in harm to a patient and are therefore not considered critical.  For example, the size or shape of a drug product,  important to commercial and marketing, are not critical to safety or efficacy.  However, impurities/degradants from an injectable product can lead to untoward adverse events and negative patient consequences. Bear in mind that identification of a potential CQA does not consider risk controls or risk management.  For example, implementing a specification to control the level of impurities and testing every batch (risk controls) and accessing and defining risk as being low (risk management) would not exclude impurities as a CQA.

Once the drug product CQAs are identified, the systematic approach e.g., a risk assessment should continue to process development, understanding the impact of critical material attributes and critical process parameters to the CQAs.  A risk-based approach (ICHQ9) over the development lifecycle will help to further identify CQAs to ultimately implement an appropriate control strategy for drug substance and drug product. The CQA control strategy and justification should be described in the appropriate sections of the regulatory dossier, 3.2.P.3.3 Description and Manufacturing Process and Process Controls, 3.2.P.3.4 Control of Critical Steps and Intermediates, and 3.2.P.5.4 Control of Drug Product.

Chamow & Associates assists companies to develop biologics for clinical testing and welcomes your inquiry.

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