Our emerging biotech and biopharma clients often request support from our skilled consultants and practitioners to develop a “Stage-Appropriate cGMP Quality System”. However, we find that they are often not fully aware of what “stage-appropriate” means or what it looks like. They know they don’t need a quality system as comprehensive as what is in place at other large commercial companies (or as large as the one they remember from their last company), but they’re not sure what to trim or where to focus the initial quality management system controls.
What Is a Stage-Appropriate Quality System?
A “stage-appropriate quality system” emphasizes the critical quality system attributes required during each phase of a company’s product lifecycle. It is designed with an understanding that the strategies for managing quality change over time as a company progresses from one phase to the next. Thus, the initial setup of the quality system needs the flexibility to accommodate changing requirements and incorporate new guidelines to achieve and maintain cGMP compliance.
Quality System Development at Each Major Stage
Preclinical Stage
During the preclinical stage (which includes both R&D and toxicity studies), cGMP quality system requirements do not apply in the strictest sense. Companies are concurrently working to develop animal models and an optimized formulation(s). Therefore, companies need only Quality functions and controlled documentation for developed technology, sufficient to support entry into human clinical trials. For many of our innovator clients, the focus at this stage should emphasize documentation capturing the knowledge gained from early experiments and decisions that were made.
Clinical Stage (Phase 1 & 2)
As a company moves to clinical trials, focus for the quality system should shift towards establishing adequate controls for the critical quality attributes (CQAs) selected to manufacture the GMP product. This ensures product quality and patient safety. Development of detailed batch records with in-process controls and acceptance criteria is an important step, as are procedures for addressing deviations, investigations, CAPAs and other non-conformances. This is also the time to introduce a well-defined change management procedure at all GMP manufacturing facilities, and to establish a formal quality assurance unit that takes a more active role in directing investigations and approving CAPAs.
Commercial Stage (Phase 3 & Beyond)
Priority shifts again when companies enter Phase 3 clinical trials that lead to commercialization – this time a shift to risk-assessed quality management. Developing a formal change control program is an important step for assessing and eliminating risks to product quality and patient safety because changes will need implementation. Companies must also ensure that manufacturing processes, PPQ batches, and analytical methods are fully validated. They should empower the Quality unit to function independently of production/operations and include oversight of both QA and quality control (QC) responsibilities. As products progress towards commercialization and launch, organizations should also add procedures for addressing customer complaints, market incidents, and product recalls.