As we enter 2011, the pharmaceutical industry has quite a reputation to repair. Throughout 2009 and 2010, some of the most
trusted and well-branded drug manufacturers were forced to issue major recalls and explain a series of poor choices. Johnson
& Johnson (New Brunswick, NJ) and its McNeil Consumer Healthcare unit, for example, recalled hundreds of millions of bottles
of popular over-the-counter pain and cold and allergy products, including many children's medications, because active ingredients
were tainted or otherwise compromised. The company also allegedly hired contractors to buy up products off the shelves before
issuing a formal recall. Amgen (Thousand Oaks, CA) recalled certain injectable products for treating anemia because of delaminated
glass vials, and Abbott (Abbott Park, IL) issued recalls of infant formula because of contamination by beetle larvae.
IMAGE: INFLUX PRODUCTIONS, PHOTODISK, GETTY IMAGES
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:
- Harmonizing key operational processes across facilities (e.g., corrective and preventive action [CAPA], management review,
investigations, supplier management, and change control)
- Improving communication across facilities with such actions as periodic cross-facility reviews
- Interchanging key personnel (particularly high-potentials) to further foster knowledge sharing and harmonization
- Adopting common metrics and performance indicators
- Investing in enterprise-level tools to facilitate communication and global information exchange.
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.