The flurry of recalls, along with a series of contamination and adulteration events caused by weak links in the pharmaceutical supply chain (e.g., heparin and melamine) have placed a spotlight on the pharmaceutical industry's management of quality control and systems. Congress has begun to question more intensely the accountability of industry as well as the effectiveness of the US Food and Drug Administration. And the US Government Accountability Office has issued more than one report suggesting that FDA needs to strengthen its oversight (1, 2). Indeed, FDA issued in July 2010 a strategy document that conveys its intent to strengthen its enforcement actions (3) (see FDA Discusses Current and Future Take on Compliance Q&A in this month's Cover Story, "Outlook 2011").
For its part, industry is paying a lot of attention to supply-chain management, including the way in which it audits suppliers and shares information. Manufacturer-led consortiums such as Rx-360 are promoting innovative programs, including audit sharing. Standard-setting organizations such as the International Pharmaceutical Excipients Council are broadening their international efforts to harmonize best practices for safe raw materials and distribution. To avoid another series of recalls, industry also seems to be looking for ways to strengthen its management of quality systems and of manufacturing deviations. Companies are exploring better ways to detect problems during manufacture and are seeking best practices for handling situations when something does go awry.For example, as a result of the released FDA enforcement strategy document, some drug companies are identifying additional process issues to monitor, says Jim Prutow, healthcare partner at PRTM, a global management-consulting firm based in Waltham, Massachusetts. These include:
Pharmaceutical Technology spoke with experts involved in these issues to gain a sense of how industry is changing the way it prevents and handles manufacturing deviations. The following sections provide a look at some forward-thinking tactics.
Understand and integrate systems
For starters, it is important that companies understand the difference between a CAPA system and a deviation system and how they work together. The CAPA system is intended to manage the correction or prevention identified to resolve the deviation, whereas the deviation system is to be used for the identification of a variation and the subsequent investigation, explains Judy O'Hara, senior consultant at Parexel Consulting, a business unit of Parexel International and a global consultancy serving the biopharmaceutical and medical-device industries .
"Resolving an issue identified through the deviation system begins with the discovery of an issue and ends with the identification of the root cause(s)," she says. "The CAPA system picks up from there. Too many times, there is a disconnect between the deviation, the root cause, and CAPA. It is important that the department responsible for the investigation, along with the Quality department, make certain that the root cause addresses the deviation and that the CAPA addresses the root cause.
Adds William (Al) Kentrup, vice-president of manufacturing and supplier quality assessments at Pfizer (New York), "In some simple cases, a simple corrective action may be all that is warranted. However, in most cases, there is typically a one-to-one or one-to-many type of relationship between corrective and preventive actions." An automated CAPA process can help link and categorize deviations in such situations on a more consistent basis, explains Kentrup. Then, the events can be trended to direct further preventive actions such as financial investments, revalidation activities, or personnel training.
It's also important to be aware of the cross-functionality of global sites and systems, says O'Hara. FDA's enforcement strategy document has highlighted this connection. The agency is "evaluating the impact of manufacturing deviations on other sites and performing a systematic review to ensure that the same issue is not occurring or does not have the potential to occur. Any identified gaps result in actions to prevent or reduce the probability of occurrence.