A crucial but often overlooked step in bringing new medicines to patients is something called Process Performance Qualification (PPQ). This is when a drug company must show that their process can reliably make high-quality products at a large scale. PPQ is especially challenging for cell and gene therapies because they are complex and can vary a lot. ‘The natural differences in biological materials can make it hard to achieve the consistency needed for successful PPQ,’ says Hiren Patel, a quality manager at MilliporeSigma. ‘Instead of the usual three-run validation, you need a solid plan, good communication with regulators, and smart use of data to create a strong PPQ campaign.’ PPQ for these therapies is also complicated because the rules and guidelines are still evolving. However, regulators are becoming more flexible and are willing to consider different types of data. This makes early and frequent talks with regulators even more important. While validating these manufacturing processes is always complex, choosing the right partner can help manage risks and speed up the process. Three Ways to Make PPQ Easier If stakeholders approach PPQ with a ‘just check the box’ mentality, delays and issues are more likely, especially for biologics and cell and gene therapies. Here are three ways developers can avoid these problems. 1. Plan for PPQ Early and Thoroughly Creating a Process Validation Master Plan is a good practice, but sponsors should define their overall PPQ strategy as early as possible. Setting clear goals helps set specific requirements for everyone involved. When sponsors and their partners agree on responsibilities and documentation from the start, PPQ execution will be smoother. It’s also important to make process characterization studies as detailed as possible. ‘The more you understand the variability in your process, the better you can control it to ensure consistent product quality,’ says Patel. Many issues that can derail PPQ can be anticipated. For example, supply chain disruptions can happen, making it hard to secure the raw materials needed. ‘Prepare for the worst,’ says Patel. ‘Stock enough raw materials and supplies to support more runs than you had initially planned.’ 2. Focus on Process Quality and Continuous Improvement A strong process control strategy is essential for successful PPQ. Important quality attributes and process parameters should be defined using Quality by Design principles. Your partner should be able to show that process parameters have been properly classified and that the most critical ones are being monitored. A good quality management system helps ensure that clear policies, standard operating procedures, and oversight mechanisms are in place. This also supports well-designed change control, supplier management, and employee training programs. ‘Manufacturers should conduct a Failure Mode and Effects Analysis early on,’ says Patel. ‘This helps identify potential problems and take steps to prevent them.’ As regulators become more open to adjustments, they are placing greater emphasis on ongoing process verification. To prepare, manufacturers must monitor their processes with an eye toward making improvements over the long term. ‘You should always be monitoring your process parameters,’ Patel explains. ‘This way, you can investigate any shifts in the process as soon as they happen.’ 3. Use Data and Analytics Throughout Process Validation Your partner should use statistical tools to analyze process data and assess variability to provide greater confidence in process performance. ‘In cell and gene therapy manufacturing, relatively few batches are produced,’ Patel says. ‘Because of this, it’s especially important to extract as much insight as possible from the data you do have.’ Manufacturing processes and analytical methods are still maturing, so limited historical data and platform knowledge are available. This gives manufacturers some freedom at a time when opportunities to engage in discussion with regulators are also increasing. ‘It’s becoming more common to have conversations about why certain decisions were made,’ Patel says. ‘When you can answer these kinds of questions—and you have the right documentation—it’s easier to meet regulators’ expectations.’ By selecting a partner with deep expertise in process validation, developers can reduce the stress and uncertainty that PPQ would otherwise bring. ‘Our Process and Analytical Department has the latest technology and state-of-the-art equipment,’ says Patel. ‘Our expert teams bring the same focus on quality to tech transfer and manufacturing. Our site prioritizes staying up-to-date with the latest regulatory changes so that processes can continue to meet compliance requirements.’ MilliporeSigma has been a leader in viral vector manufacturing for more than 30 years and has supported four commercially-available viral vector-based gene therapies. As a viral vector CDMO, MilliporeSigma offers comprehensive regulatory support and specialized technical expertise to make the transition from clinical to commercial manufacturing seamless.