To launch a successful GMP program for biologics, a robust quality control (QC) release testing protocol is essential. QC testing, which is mandated by global regulatory authorities, helps ensure that a product meets scientific specifications and reaches patients safely. Though each program will have unique parameters, QC testing should gather data to answer the following questions:

  • Identity: Have you produced the correct product? 
  • Purity: What manufacturing and product byproducts are present? 
  • Strength: What is the potency and quantity of your product? 
  • Safety: Is your product safe and free of unwanted adventitious agents, e.g. Virus, bacteria, and mycoplasma? 
  • Product Quality Attributes: Have you demonstrated that product specific attributes are present? 

As biologics continue to diversify beyond monoclonal antibodies (mAbs) and recombinant proteins to include cell and gene therapies (CGTs), QC programs are shifting to accommodate the unique challenges associated with these advanced and novel therapeutics.

Recognizing Important Shifts

CGTs require adaptive and advanced assays for characterization and safety assessments; in many instances, the assays historically used for biologics do not fit the needs of these novel therapies. For example, mycoplasma has long been an area of key testing concern due to its ability to pass through standard sterilization filters. The standard mycoplasma culture-based assay takes 28 days to complete. This cycle is incompatible with the short shelf life of CGT products; as a result, the industry has pivoted to PCR testing for mycoplasma in CGTs, which can be completed in just a few days.

Empty/full ratios for viral vectors are another critical quality characteristic that has been challenging to characterize in the GMP setting thus far. To date, Analytical ultracentrifugation (AUC) has served as the best assessment of empty, full, and partial populations on the market, and as the identification of these ratios grows increasingly vital, AUC will continue to be an important implement for QC programs.

Several other considerations, including defining the critical quality attributes of raw materials and navigating evolving regulatory guidance, have left CGT developers and manufacturers looking for greater insight into how best to design their QC approach.

Identifying Five Best Practices for QC Programs

As you strive to design a strategic QC program, assess how you can leverage the following five best practices in your approach:

  1. Align to Your Risk Assessment:To mitigate risk, begin with a GMP mindset from the start, including sourcing well-characterized cell lines and raw materials while accounting for scale in your processes.
  2. Take a Quality by Design (QbD) Approach: Implementing QbD processes entails several deliberate choices, including ensuring you have the inventory necessary for your product lifecycle, creating a reference standard, and tracking trends as you set specifications.
  3. Leverage Templates and Platforms: Utilizing a templated or platformed approach helps you minimize variation in your process and establish streamlined validations, defined assay parameters, and a thorough understanding of each step.
  4. Gain Proximity to the Manufacturing Floor: The closer the QC lab’s proximity to the manufacturing floor, the better. The goal is to implement real-time, continuous testing in parallel with your manufacturing process.
  5. Participate in Knowledge Sharing: Disseminating key findings between stakeholders across the industry ― particularly around data, technology, and regulatory interactions ― yields major benefits for everyone, including patients.


Where Can I Learn More?

If you’d like more insight into improving your QC program, Dr. Audrey Chang, Executive Director at WuXi Advanced Therapies, recently hosted a webinar in which she highlighted the difficulties of developing QC programs for CGTs and her recommendations for how to improve them. You can watch the full webinar here or contact us to schedule a time to speak with her directly.

 [CD1]Link to be added once webinar summary is live.