Process Validation/

Process Qualification
Process Validation comprises 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 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 FDA and EMA have issued guidance on Process Validation and although their terminology may differ, the main objective – a process design that yields a product meeting its pre-defined quality criteria –  remains the same.

The Process Qualification stage consists of two elements:

  • Design of Facility and qualification of the facility, utilities and equipment to demonstrate suitability for its intended use and proper performance.
  • Process Performance Qualification (PPQ) to confirm process design and to demonstrate that the manufacturing process performs as expected.

The complete Process Qualification stage should be executed according to GMP regulations.

Traditionally, PPQ is performed after development has been concluded, and prior to the marketing of the finished product. PPQ is preferably executed at a commercial scale, but if justified it can also be conducted on a pilot scale. In some cases it is necessary to include validation data from production scale batches in the regulatory dossier, e.g. for a biological / biotech product. PPQ batches are evaluated against predetermined acceptance criteria, including specifications for quality, safety, and efficacy and comparability with relevant studies.

In exceptional circumstances it may be acceptable to start routine production before completion of the validation program. 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 PPQbatches required, a rational and justified decision based on product knowledge and process understanding is expected from manufacturers. The overall residual risk level associated with the manufacture should be assessed based on product knowledge, process understanding, and small (pilot) scale/clinical manufacturing experience.The residual risk should then be translated into the number of required PPQ batches.

Conducting a PPQ is certainly not a ‘copy-paste’ exercise. Knowledge of laws, regulations, guidelines, and progressive regulatory expectations from international and national authorities is essential, together 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 should be confident that the PPQ batch(es) will meet the pre-determined quality requirements.

During inspections and regulatory review of process validation reports one or more of the following observations are frequently made:

  • Inadequate process validation procedures and documentation
  • Inadequate validation of new filter types and filtration times, and holding times.
  • For intermediates, an absence of criteria for specified impurities and a failure to validate the reduction of these impurities in the upscaled process.

Having to perform additional PPQs can seriously delay market launch or product supply.

How can we help
Progress consultants are experienced in all aspect of Process Qualification. They can support your organization with:

  • Defining a qualification strategy for utilities and equipment and support with its execution. Writing and review of all required documentation, e.g. URS, IOQ protocols and report, PQ protocols and reports.
  • Setting up a process qualification strategy, e.g. justification of the number of PPQ runs and batch size(s).
  • Writing of all required documentation (e.g. overall summary reports, PPQ reports, product characterization/impurities reports) and Regulatory submission documentation.
  • Performing a Quickscan/GAP analysis to determine the status of deliverables required at each stage of the project.
  • Ensuring that the process qualification is executed conform GMP regulations.

Our approach
Progress is specialized in project management for pharmaceutical and biotechnology companies. Each project demands a different kind of approach and strategy. Our experienced project managers are Prince2®certified, pragmatic and customer-focused.

Progress consultants can support your goals to produce drug products which fulfill all quality requirements during the whole lifecycle of the product. With their Process Qualification experience as well as their manufacturing process upscaling expertise in combination with their GxP knowledge, they can fully support you in the Process Validation of your manufacturing process as required by the regulatory agencies.


  • Process Validation: General Principles and Practices: Guidance for Industry, FDA 2011
  • ICH Q8 (R2) Pharmaceutical development
  • ICHQ11 Development and manufacture of drug substances
  • Annex 15 EU Eudralex