Removing bottlenecks

On-line monitoring, linked to an infrastructure that integrates a company's various data systems, can provide personnel with excellent visibility of the manufacturing process. But the wealth of information that this infrastructure provides, coupled with memories of production problems that have brought regulatory scrutiny, can prompt pharmaceutical manufacturers to be overly cautious with their CAPA programs. "Not all deviations will be CAPAs. I think a lot of people tend to funnel all their deviations into the CAPA system, and that's not necessarily appropriate," says Schniepp. A deviation should lead to a CAPA only when the result of that deviation would affect the product's quality and safety.

A common problem in CAPA programs today is many companies' failure to distinguish crucial from noncrucial events. "Events in a quality system often always become a CAPA, until the company has more CAPAs than it can manage effectively," says Tim Lozier, manager of strategic development at EtQ (New York). As a result, manufacturers often focus on addressing the most overdue CAPAs rather than completing those that represent the most crucial events. The excess of CAPAs can create a bottleneck in an otherwise healthy quality system.

A cosmetic error such as a smudged logo on a finished product may not be deemed crucial, especially if it occurs in a single lot, and can be immediately corrected. Less crucial events are handled in the event record. A mislabeled finished product, however, can have a higher risk ranking and be deemed crucial. The definition of a crucial event can vary from company to company, depending on each manufacturer s history.

The industry is beginning to accept this risk-assessment approach to CAPA as the best practice. For some pharmaceutical manufacturers, crucial process-parameter deviations automatically trigger a CAPA process. The number of noncrucial deviations that triggers a CAPA process depends on the culture of the particular company, says Lenich.

Automation for all?

A fully automated CAPA process helps pharmaceutical manufacturers in different ways, and to different degrees, depending on their size. Although small, medium, and large drug companies face similar regulatory scrutiny and compliance challenges, the resources available to these companies differ, which may explain why pharmaceutical manufacturers have embraced automation to different degrees.

Automation is not necessarily cost effective for companies with 100 employees or fewer, says Schniepp. Setting up automated CAPA systems can be time consuming and might not provide many advantages to firms that manufacture low volumes of a small portfolio of products. Instead, small drugmakers are likely to rely on their contract manufacturing organizations (CMOs) to track CAPAs.

The extent to which small companies are automating their CAPA processes is unclear. Small companies do stand to benefit from automation, says Lenich, but they often view automation as a cost rather than as a value. This perception is a salient distinction between small drugmakers and mid- to large-sized manufacturers.

Even if they cannot automate their CAPA systems fully, smaller companies can find automation for specific parts of the CAPA process, which may help them address performance concerns and focus on continuous improvement, says Kentrup. "The challenge is to determine a prioritization scheme for automating parts of the process that is consistent with expected business outcomes," he adds. Considerations that would promote the automation of a CAPA system include minimizing the initial financial investment, monitoring process performance, and containing capital-investment costs.

It can be difficult for mid-sized pharmaceutical companies to determine how cost effective it is for them to implement an automated CAPA system, partly because they are uncertain about whether their products will reach the market. A mid-sized company with a mixture of small- and large-molecule products will likely want to track the active-ingredient manufacturer, final-product manufacturer, and packager for each late-stage product. If the company hires 12 CMOs to provide four products, it might consider automating its CAPA process to keep track of its contractors' operations, says Schniepp.