The Quality-by-design approach has some clear advantages over the traditional methods of process validation in the pharmaceutical industry, according to Michael R. Goodman, compliance specialist, Compliance Insight. These are:
·Mitigating potential risk
·Maximizing understanding of the process
·Establishing in-process controls
Goodman explains that until 1990, pharmaceutical firms used the 'Quality by QC' (or 'quality after design') approach. The Quality-by-design approach would require introducing a 'fragmented' approach to process development, focus on the importance of process development with regards to process validation, and encouraging risk-mitigation through predicting potential problems from internal and external forces.
In simple terms, the traditional approach of process validation emphasized after- and in-process inspections. But the new Quality-by-design is based on the premise that the quality of any pharmaceutical dosage form or drug can actually be planned.
The Quality-by-design approach makes it easier to focus on:
·Raw Material – Monitoring every aspect of the raw material including packaging. It includes monitoring all ingredients and chemicals used.
·Equipment – Emphasis on regular monitoring of manufacturing machinery with proper calibration, maintenance, and meeting fill-control targets
·Manufacturing Processes – Emphasis on designing and implementing the best-possible manufacturing process. Automated manufacturing is preferred to handling of the drugs by humans.
·Checks and controls – Critical measures to ensure the best quality in the final product. These involve automation too.
Take a case study like the development of the polio vaccine. The process involved Polio Myelitis Protocol development by Jonas Salk, successful clinical trial, clinical trial vaccine formulation by Eli Lilly and Parke-Davis, subsequent process licensing to five companies for commercially manufacture of vaccine. Cutter Laboratories were given the task of ensuring 11 consecutive batches of inactivated virus before vaccine could be commercialized.
Cutter Laboratories vaccine was used in 380,000 children. Of these, 40,000 children developed polio symptoms, 51 children were completely paralyzed following dose, 5 children died, and 113 additional people were paralyzed (5 died). Government health agency determined two production pools (120,000 doses) contained live virus.
Problem was that Cutter Laboratories used glass that was inconsistent and they did not characterize viral reduction curve over time. There was evidence that Cutter Laboratories did not manufacture 11 consecutive batches. It was 'Liability without Negligence'. The process would have been completely different with the new approach.
Adding Quality-by-design to the procedure would be like turning art into science. The new approach would include Quality by Design – Process Development, Process Analytical Technologies, and Corrective and Preventive Actions (CAPA).
Compliance Insight, Inc. specializes in Regulatory and Quality Assurance consulting and training for pharmaceutical, nutraceutical, medical device, chemical, and bio-technology companies in North America, Europe and Asia.
For more information visit http://www.compliance-