Cell therapy offers a revolutionary approach to treating and curing diseases. But that potential comes with a high level of complexity—one that developers grapple with throughout the manufacturing process.
One of the most pressing challenges is quality control (QC). Manufacturers follow stringent QC measures to ensure the safety, efficacy, and consistency of the final product. However, unlike conventional pharmaceuticals, cell therapies are living products that cannot undergo final product sterilization, and they are often produced in small batches, limiting the final product available for testing.
The good news is that developers can achieve consistency with QC checks throughout production. Here are the essential components of a cell therapy sampling plan, and how a CDMO can help developers maintain a high level of safety and efficacy during manufacturing.
A Robust In-Process Testing Plan Starts with a Winning Strategy
A successful in-process testing plan begins during product development, with a strong understanding of both product and process.
Developers should set product parameters and establish the standards to measure samples against during manufacturing. These include the quality target product profile (QTPP), along with critical quality attributes (CQAs), for optimal safety, identity, purity, quantity, and potency.
Understanding the process means characterizing and validating it to establish the operating ranges for various critical process parameters (CPPs). By defining how these parameters impact production—and then the CQAs—developers can identify which parameters need to be monitored and controlled for highest quality.
From There, Developers Can Execute a Six-Stage Testing Plan
Once developers have outlined product and process quality standards, they can deploy in-process sampling for quality control.
The ideal plan should:
1. Outline How CPP Influence CQAs for the Product
Developers should develop an early understanding of how CPPs—temperature, pH, and nutrient concentrations during cell culture—influence downstream CQAs, such as cell viability, identity, potency, purity, and sterility.
Developers can use these data to devise a testing plan that identifies in-process controls (IPCs), sampling timepoints, specifications, and acceptance criteria to ensure the consistent production of high-quality cell therapy products.
2. Implement Real-Time Monitoring
Real-time monitoring is essential for maintaining control throughout production.
Techniques such as flow cytometry, PCR, and ELISA can monitor cell characteristics and detect deviations from the desired CQAs. By monitoring real-time data, developers can spot and address variability during manufacturing—and prevent substandard final products.
Technology can help staff collect and analyze data in real time. Automated imaging and machine learning can detect anomalies quickly, allowing for rapid intervention.
3. Establish In-Process Controls (IPCs)
IPCs are checks performed during the manufacturing process to ensure each step is completed correctly and consistently.
IPCs should be selected based on the most important CQAs, and cover every critical stage of production, from cell isolation and expansion to final formulation. For example, manufacturers might opt to monitor cell growth rates, check for contamination, and verify purity when producing a cell therapy product.
4. Validate Analytical Methods
The reliability of in-process testing lies in validating analytical methods. Without proper validation, manufacturers may unintentionally add variability to the process, which could affect the final product. They may also face regulatory challenges as they approach commercialization, since analytical validation is critical for gaining approvals from health authorities.
Process validation is a little different. It ensures that the methods used are accurate, precise, specific, and reproducible. This involves rigorous testing under various conditions to confirm that the methods consistently produce reliable results and yield a consistent product.
5. Ensure Data Integrity
Data integrity is a cornerstone of a robust in-process testing plan, and all data generated during the manufacturing process must be accurate, complete, and traceable.
Manufacturers can maintain data integrity by implementing an electronic data management system. This provides secure, real-time access to data and ensures compliance with regulatory standards. In addition, manufacturers should conduct regular audits and reviews of data management practices to identify and address potential issues.
6. Continually Improve and Adapt the Strategy
In a fast-moving field like cell therapy, in-process sampling should be an iterative process as new knowledge comes to light. Developers should regularly review and update the testing plan based on new scientific insights, technological advancements, and regulatory changes. This approach ensures that the manufacturing process remains robust, and it allows developers to keep pace with innovation as the field progresses.
How a Contract Development and Manufacturing Organization (CDMO) Can Help
Developing and executing a robust in-process testing plan requires access to both advanced technologies and specialized expertise. As a result, many developers find it cost-prohibitive to execute their manufacturing and sampling plan in-house.
By partnering with a CDMO, developers can devise an effective in-process testing plan and set phase-appropriate specifications to set their program up for success. Here’s how.
Extensive Expertise and Experience
Achieving consistency in manufacturing cell therapies requires in-depth expertise, and a CDMO can be a trusted partner in this.
A CDMO can help identify the best CQAs to ensure product quality and help design tests to monitor and control these parameters during the manufacturing process. CDMOs are also well versed in applying design of experiments (DoE) approaches to understand how multiple inputs interact with each other. This can define operating ranges that ensure consistent performance from early in development.
Tools such as failure mode and effects analysis (FMEA) are also routinely employed by CDMOs to determine attributes that affect product performance most critically.
Devising Customized Solutions Based on the Program’s Unique Needs
Every cell therapy product is unique and comes with its own set of QC challenges. CDMOs can offer custom strategies that address the specific needs and challenges of each product, ensuring a tailored approach to in-process testing.
Providing Access to Advanced Analytical Methods
CDMOs offer access to advanced analytical technologies—those that would be cost-prohibitive to set up in-house. As a result, CDMOs can implement real-time monitoring techniques such as flow cytometry, PCR, and automated imaging to ensure precise and timely quality control.
Facilitating Discussions with Regulatory Agencies
Cell therapies come with a number of regulatory challenges—and a CDMO partner can help navigate them. CDMOs provide guidance on regulatory compliance, helping clients understand and meet the necessary standards. And they assist in preparing documentation and engaging in discussions with regulators.
Ensuring Consistency with Method Validation
CDMOs can validate analytical methods to ensure they are accurate, precise, and reproducible. This is crucial for regulatory approval and the reliability of in-process testing.
Following Best Practices for Data Management
Data integrity is key to the success of any cell therapy program. CDMOs can implement robust data management systems for manufacturing that provide secure, real-time access to data, which can help ensure compliance with regulatory standards and facilitate audits.
Continually Improving and Refining the Testing Strategy
Leading CDMOs keep their finger on the pulse of the latest scientific and technological advancements in cell therapy manufacturing. This means they can keep up to date on the best practices for in-process testing, helping ensure consistent performance over time.
The bottom line
While cell therapies come with unique QC challenges, robust in-process testing can help developers consistently produce safe and effective therapeutics that ultimately boost patient outcomes. For many biopharmaceutical brands, though, partnering with a CDMO is essential to access the technologies and expertise required to achieve—and prove—the required level of consistency.
We’re Here to Support Your Cell Therapy Program
Our team of cell therapy experts can help developers build robust in-process testing plans tailored to the unique needs of each program—and help you achieve success in cell therapy manufacturing. To learn more, visit us online.
Catalent, Inc. is a leading global contract development and manufacturing organization (CDMO) championing the missions that help people live better and healthier lives. Every product that Catalent helps develop, manufacture and launch reflects its commitment to improve health outcomes around the world through its Patient First approach. Catalent provides unparalleled service to pharma, biotech and consumer health customers, delivering on their missions to transform lives. Catalent tailors end-to-end solutions to meet customers’ needs in all phases of development and manufacturing. With thousands of scientists and technicians and the latest technology platforms at more than 40 global sites, Catalent supplies billions of doses of life-enhancing and life-saving treatments for patients annually. For more information, visit www.catalent.com.
