USP <790> is a critical chapter for the visual inspection of injectable and parenteral medicines, ensuring that products are free from harmful particulate matter. While it serves as a foundational and enforceable standard in the pharmaceutical industry, applying USP <790> to cellular therapeutics presents unique challenges. Despite these difficulties, therapeutic developers and Contract Development and Manufacturing Organizations (CDMOs) can still leverage elements of USP <790> to implement effective lifecycle approaches for particulate management and control.
Challenges in Applying USP <790> to Cellular Therapeutics
Several factors complicate the application of USP <790> to cellular medicines:
Small Volume Inspection: Therapeutics delivered in small volumes are inherently challenging to inspect visually. The limited quantity makes it difficult to detect particulates accurately.
Cellular Properties: The cells themselves act as particles, obscuring the visual inspection for extrinsic (external) and intrinsic (internal) particulates. This intrinsic property complicates the identification of unwanted particles.
Overall Appearance: The complex appearance of cellular therapeutics makes visual inspection challenging. The nature of these products can inherently mask particulates that would otherwise be detectable.
Container-Closure Systems: Common container-closure systems for cell therapies, such as cryopreservation bags, present additional inspection difficulties. These systems are not as transparent or easy to inspect as traditional vials or syringes.
Implementing a Lifecycle Approach for Particulate Management
Despite these challenges, several strategies can be employed to assess and manage particulate matter in cellular therapeutics:
Risk Assessment and Demonstration: It is crucial to assess the risk and demonstrate the impact of extrinsic and intrinsic particulates. This involves understanding how particulates affect the product and patient safety.
Rinsing and Flush-Out/Wash-Out Studies: These studies help in assessing the presence of particulate matter. By thoroughly rinsing and flushing out the container, developers can identify and quantify particulates.
Particle Population Counting and Sizing: Accurate counting and sizing of particles provide essential data on particulate matter presence and distribution. This data is vital for understanding the extent of contamination and for developing control strategies.
Particulate Matter Identification/Characterization: Identifying and characterizing particulates are necessary steps in understanding their source and impact. Advanced analytical techniques can help in this process.
Creating Reference Material Libraries: Developing libraries and databases of reference materials is a proactive step. These libraries catalog all product contact materials and their contribution to particulate matter, aiding in future investigations and control efforts.
Cataloging Particulate Matter: All characterized extrinsic and intrinsic particulate matter should be documented in a particulate matter database. This database tracks and trends particulate matter excursions, facilitating effective control of future contaminations.
Applying USP <790> to cellular therapeutics involves navigating several unique challenges. However, by adopting a lifecycle approach and employing targeted strategies, therapeutic developers and CDMOs can effectively manage particulate matter. Conducting thorough risk assessments, employing advanced analytical methods, and creating comprehensive databases are critical steps in ensuring the quality and safety of cellular therapeutics. Gateway Analytical is here to support developers in overcoming these challenges, offering expertise and solutions for effective particulate matter control.
Explore how Gateway Analytical can support your journey to market. With over a decade of expertise in parenteral testing, we cover a broad range of services from process and formulation development, product-package validation, clinical & commercial manufacturing, to visual inspection, quality control, and release testing. Reach out to our experts at (724) 443-1900 or info@gatewayanalytical.com, or feel free to visit our contact page to connect with us!
