By Agnes Shanley

 At IFPAC 2012 the 26^th International Forum for Process Analysis and Control, Richard Friedman, Associate Director of FDA’s CDER’s Compliance Office’s Office of Product Quality, spoke of the need for pharma to modernize the way it controls manufacturing processes and assesses quality risks. 

 By modernizing, he suggested, the industry would be embracing the true spirit of ICH Q10, with its emphases on change and knowledge management, and innovation.

 Citing Jim Colton’s article on statistical quality tools for pharmaceutical manufacturing in December 2011’s issue of  Quality Digest, Friedman quoted CDER director Janet Woodcock on the need to think of the primary customers, the people taking medicines, when manufacturing.  He also noted the importance of reconciling the producer’s risk, of rejecting product of adequate quality, with consumer’s risk, of accepting defective product. 

 Voice of the Customer
The voice of the customer should be the foundation for quality efforts he said, and patient-focused quality systems require senior management commitment.  “Quality is better assured when management recognizes and leads with the understanding that upstream controls make good business sense.

 With the right controls in place, he said, a proactive Quality Assurance culture will supplant the antiquated Quality Control paradigm. 

 The test of any Quality System is whether or not it can catch a problem in a batch during production rather than after the product has been placed on the market, he said.   Today, he said, mistakes are not often caught by individuals who make the error but through QC tests, which are of limited sample size or sensitivity. The industry needs a “redundancy of controls,” or process analytical technology (PAT), he said.

 In order to get there, managers must see how GMPs align with basic business goals of process predictability and product dependability.  Friedman referred to Deming’s Chain Reaction, in which reducing variability and improving quality decreases cost, improves product quality and increases company competitiveness. He reiterated the fact that identifying gaps, and root causes of quality problems, an area where recent FDA citations have faulted many facilities, is simply good business.

 Friedman referred to last year’s survey by ISPE and PDA on the cost of pharma noncompliance,  in which 51% of respondents found that cost was a “significant factor” in decisions on whether or not to fix potential quality problems, yet 41% if respondents noted that proactive fixes cost 1/10 as much as reactive ones to achieve (Chart).

Common causes of compliance problems, he said, are deficient facilities and processes, including old platforms, and lines that require frequent stops and starts.  He contrasted open vs. closed (Chart), manual vs. automatic, and emphasized the importance of facility design, especially for biopharmaceuticals, where issues such as viral clearance, containment, flow of materials, sterilizing and cleaning, and storage and handling are of critical importance.  For drugs that aren’t well characterized, and for microbiological quality assurance, there is a need for redundant controls.

Friedman also examined human error and material variability as contributors to variable pharmaceutical quality,  highlighting the potential impact of excipient variability (Chart). 

He considered a number of scenarios, including dissolution failure due to excipients.

 In short, his presentation challenged pharma’s risk-averse managers to view risk in a different light and to modernize operations and quality control.  In the end, he suggested, modernization and innovation can only lead to improved patient safety and corporate competitiveness.

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