Critical Quality Attributes for Drug Products
This article is the fourth part of our “Best Practices in the CDMO Selection Process” series, through which we intend to provide sound advice to agile biotech companies in identifying and selecting the right Contract Development and Manufacturing Organization (CDMO) for advancing the development of their product(s), in conjunction with successfully managing a chosen CDMO to meet the company’s expectations.
In this article, we will explore the importance of Critical Quality Attributes (CQAs) in the drug development lifecycle and why it is vital that your selected CDMO is capable of addressing them.
What are CQAs?
CQAs represent the benchmark for most quality-by-design implementations. CQAs are part of the systematic development approach that begins with predefined objectives and emphasizes product and process understanding and process control. These are based on sound science and quality risk management (ICH Q8 R2).
CQAs are created with patients in mind and tied to the Quality Target Product Profile (QTPP). The QTPP includes all product quality characteristics and specifically, those critical to safety and efficacy as defined in the product label (Target Product Profile).
Quality targets serve as the basis for process development and guide the selection of process steps, material attributes, equipment design and operation controls for the manufacturing process.
How do you identify CQAs?
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 product quality (ICH Q8 R2). ICH 6A further defines CQA specifications as the criteria that a drug substance or drug product must meet to be considered acceptable for its intended use. This includes attributes like identity, strength, purity and potency.
The approach to identifying CQAs begins with identifying all quality attributes and creating the QTPP. The QTPP can be considered an expansion of the higher-level TPP.
For example, the TPP defines the dosage form as IV, whereas the QTPP includes concentration, color and clarity. Next, all the quality attributes are evaluated for severity of harm (safety and efficacy) to a patient.
Not all quality attributes result in harm to a patient and so aren’t considered critical. For example, the size or shape of a drug, while important to commercialization and marketing, is not critical to safety or efficacy. However, impurities/degradants from an injectable product can lead to adverse events (AE) and negative patient consequences.
It’s important to note that identification of a potential CQA does not consider risk controls or risk management. For example, impurities are CQA, regardless of whether testing determines the risk of impurities to be low.
Using CQAs to inform development
Once 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 identifies CQAs and informs an appropriate control strategy for drug substances and drug products. 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.
The right CDMO should be able to assist you in addressing identified CQAs from an analytical perspective throughout the process development and manufacture.