Process Validation/
PPQ
Process Qualification
The Process Validation lifecycle includes Process Design (see Quality by Design and Process Development), Process Qualification and Continued Process Verification (see Continued Process Verification). Process Validation is a critical regulatory requirement and can be defined as obtaining documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce a medicinal product that meets the predetermined specifications and quality attributes. Both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have released guidelines on Process Validation and while their terminology may differ, the approach and main objective, a process design that produces a product that meets predefined quality criteria, remains the same. Process Performance Qualification (PPQ) is the term used by US FDA for the second phase of Process Validation.
The entire Process Qualification stage must be executed according to Good Manufacturing Practice (GMP) regulations and consists of two elements:
- Facility Design and qualification of the facility, utilities, and equipment to demonstrate suitability for intended use and appropriate performance.
- Process Performance Qualification (PPQ) to confirm the process design and demonstrate that the manufacturing process is performing as expected.
Traditionally, PPQ is performed after development is completed and before marketing the finished product. PPQ is preferably conducted on a commercial scale but can also be conducted on a pilot scale if justified. In some cases, it is necessary to include validation data from production-scale batches in the regulatory dossier, for example for a biological/biotech product. PPQ batches are assessed against predetermined acceptance criteria, including specifications for quality, safety and efficacy and comparability with relevant studies. In exceptional circumstances it may be acceptable to commence routine production before the Process Validation / PPQ program has been completed. In these cases, concurrent validation can be used.
There is no fixed number of process qualification batches to be performed. To determine the number of required PPQ batches, manufacturers are expected to make a rational and justified decision based on product knowledge and process insight. The overall residual risk level associated with manufacturing should be assessed based on product knowledge, process understanding and small-scale (pilot)/clinical manufacturing experience. The residual risk must then be translated into the number of PPQ batches required.
Conducting a Process Validation / PPQ is certainly not a ‘copy-paste’ exercise. Knowledge of laws, regulations, guidelines, and progressive regulatory expectations of international and national authorities is essential, along with an in-depth knowledge of the product, process, and analytical methods. The purpose of PPQ is to confirm product quality and process consistency. Therefore, before commencing PPQ runs, the manufacturer must be confident that the PPQ batch(es) will meet pre-determined quality requirements.
During inspections and regulatory review of Process Validation / PPQ reports, one or more of the following observations are often made:
- Inadequate process validation procedures and documentation
- Inadequate validation of new filter types and filtration times and holding times.
- For intermediates: the lack of criteria for specified impurities and the inability to validate the reduction of these impurities in the scaled-up process.
Having to perform additional PPQs can seriously delay market launch or product supply.
How can we help
Progress consultants have experience with all aspects of Process Qualification. They can support your organization with:
- defining a utility and equipment qualification strategy and supporting its implementation, including writing, and reviewing all required documentation such as URS, IOQ protocols and reports, PQ protocols and reports;
- setting up a process qualification strategy, for example justifying the number of PPQ runs and batch size(s);
- writing all required documentation (e.g., general summary reports, PPQ reports, product characterization/impurities reports) and documentation for regulatory submission;
- performing a Quick Scan/GAP analysis to determine the status of the desired deliverables at each stage of the project;
- conducting the process qualification in accordance with GMP regulations.
Our approach
Progress specializes in Project Management for pharmaceutical and biotechnology organizations. Every project requires a different approach and strategy. Our experienced project managers are Prince2®certified, pragmatic and client oriented.
Progress consultants can help you produce drug products that meet all quality requirements throughout the entire product life cycle. With their Process Qualification experience and their expertise in scaling up manufacturing processes in combination with their GxP knowledge, they can fully support you in the Process Validation of your manufacturing process, as required by regulatory authorities.
