Validating Bioprocess Innovation to Exceed Regulatory Standards

As bioprocessing innovation continues, drug manufacturers face many challenges. The market is demanding more targeted, efficacious, and cost-effective therapeutics, raising the stakes for drug manufacturers. Across the industry increasingly complicated biologics, biosimilars, and cell and gene therapies are driving innovation as patient populations grow and age. Interest in continuous bioprocessing and flexible facilities are also on the rise.

Drug manufacturers must identify efficacious products and manufacture them with processes that meet regulatory requirements. The United States and Europe have continued to tighten regulations and introduce new standards for validation of regulatory compliance. In Asia, particularly in China, there is a greater focus on advanced extractable and leachable (E&L) testing and validation, than in the past. This is due to the increasing interest and implementation of single-use systems, in biologics processing. 

As global regulatory bodies evolve safety and quality requirements, drug manufacturers must demonstrate that they are in a state of control of their processes. Clear validation plans (that support scale-up or scale-out processes) and documentation of demonstrated process validation success, must be readily available, during audits. These documents are especially important when working towards Phase III or commercial production phase. It is inherent to product lifecycle management (PLCM). 

Meeting Challenges with Responsible Solutions

Many new or improved bioprocessing processes, implemented by drug manufacturers involve challenging solvents or formulation recipes. For instance, with cell and gene therapies, the liposomal carriers are potentially harder to sterilize using sterilizing grade filtration. Or they can have issues that exacerbate under processing pressure. Using traditional sterilizing grade filters might require multiple stages of filtration. Drug manufacturers must overcome these challenges while demonstrating reproducibility and control of the process from small to large scale.

Although the bioprocess validation responsibility primarily falls on the primary drug manufacturer, suppliers can share the responsibility, supporting and supplementing primary manufacturers, with small scale process or membrane validation, using the drug product or drug substance. Collaborating with the primary drug manufacturer, a holistic validation control strategy (CS) can be better developed, leading to drug manufacturers better managing their product lifecycle management strategy.

Some points for consideration during a PLCM review include:

• Review of prior and current process data, tech transfer data, validation data

• Continuous monitoring of prior established and validated critical quality attributes (CQAs), prior established and validated critical control parameters (CPPs), and established specification and process control limits.

• Pharmaceutical quality system (PQS) oversight from process feedback

For established or new processes, updates or process change controls implementing novel technology or equipment, can impact prior process validation data. Pall Biotech’s Accelerator^sm Validation Services can ease this process by conducting technical reviews with primary drug manufacturers, for validation or revalidation purposes, as necessary.