Incorporate guidelines and standards
To help prevent manufacturing deviations, manufacturers can put into practice key points from the International Conference
on Harmonization's quality-trio guidelines (Q8 Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System), advises Parexel's O'Hara. "I would suggest that companies take the time to understand the guidelines, train their staff,
and have a good implementation plan," she says. "The deviation system is just one of many valuable Quality system tools a
company should use to encourage continuous improvement, which helps not only the compliance of the company but also the bottom
The ICH quality-trio guidelines are also pushing drug manufacturers and regulators to focus more on corporate responsibility
when it comes to managing risk and potential manufacturing deviations, according to PRTM's Prutow. A key message from ICH
Q8, Q9, and Q10, says Prutow, is that "quality, safety and compliance should not to be limited to the domain of the quality
unit and compliance organizations. Rather, the ICH tripartite emphasizes that executive management must be effective at preventing
risks from spreading. Furthermore, the tripartite takes risk well beyond the product itself to the broader supply and business
domains making an enterprise risk approach more important for all pharmaceutical companies, especially when they face threats
in areas that may not have originally been expected (i.e. wooden pallets causing issues at Johnson & Johnson).
Put knowledge management to use
The ICH quality-trio also incorporates the concept of knowledge management, an idea that has been the topic of many industry
forums and conferences during the past several months. Information can be used to a drug manufacturer's benefit, according
to experts. "Companies collect data, track and trend deviations and complaints, and monitor CAPAs, but in many cases, that's
all that's done," says Parexel's O'Hara. Taking these data and actually analyzing them can yield valuable information. For
example, a company might group deviations into similar problem types and root causes and use that grouping to determine whether
a deviation is occurring in the same department, during the same shift, or when using a certain piece of equipment or certain
part of the process, she explains.
"Applying the knowledge gained from analyzing the data helps in anticipating issues or potential issues, recognizing opportunities
for improvements to processes and products, reducing rework and generating efficiencies," says O'Hara. "Individually, this
is hard to see, but once data is tracked and trended as well as reviewed collectively, this is invaluable." (See sidebar,
"In the case of recall," for information on how knowledge management can be useful in the case of recalls.)
In the case of a recall
In day-to-day manufacturing, an automated CAPA process can be interfaced with a knowledge management repository to maximize
access to the data and minimize the need for re-entering data into multiple systems, recommends Pfizer's Kentrup. "A well-integrated
CAPA system can be invaluable with regard to overall product-knowledge management by providing access to information regarding
the issues that have been addressed in one central repository or via a single link."
Knowledge management can also play a role when a company is manufacturing multiple products that share specific components
or processes, says PRTM's Prutow. "One best practice is the use of virtual dynamic centers of excellence, or user communities,
which allow sharing of practices and opportunities across a specified area, such as validations or aseptic practices. The
centers of excellence ensure knowledge of issues and best practices across the company," he explains.
Finally, involvement of management is crucial for several reasons, says Parexel's O'Hara. Management is ultimately responsible
for how the company responds to risks and the actions taken has the authority and responsibility to provide the resources
(e.g., financial, staff) to ensure that the company produces a product that is safe and effective (and in a safe and compliant
environment) and can encourage the engagement of staff, which aids in ensuring success from the design of a product to a finished
product. These three factors encourage staff to anticipate issues, and to voice their thoughts as to why or how a deviation
occurred and aid in CAPA. Their knowledge and experience is invaluable in the deviation and CAPA systems processes.
Don't overlook the supply chain
Beyond the manufacturing floor, it's crucial for quality teams to pay attention to raw-material sources and potential supply-chain
gaps at the international level. For example, explains Jian Liu, PhD, associate professor of the Eshelman School of Pharmacy
at the University of North Carolina. Liu has researched extensively the heparin contamination of 2008, which was largely the
result of a shortage of pigs (their intestines are used to manufacture the blood-treatment product).
It should not have been a surprise to drug companies that "the worldwide production of heparin exceeds 100 tons/year, which
is isolated from 500 to 700 million pigs, and that the entire US pig production is only about 60 to 65 million/year," says
Liu. When the pig shortage started to gain traction, manufacturers should have been looking for potential counterfeit problems.
A key lesson learned from this incident, says Liu, is that, "Manufacturers must monitor the quality of products from suppliers
and have adequate controls in place to prevent the counterfeits, especially those highly sophisticated counterfeit products
(i.e., such as the oversulfated chondroitin sulfate used in the heparin contamination).
In order to reduce risks associated with material sources, industry and regulators might also consider enforcing "high purity
standards," says Liu, For example, after the heparin crisis, FDA and the US Pharmacopeia worked to revise the heparin monographs
to contain higher purity standards. Such standards, however, can be a double-edged sword, he says, because excessively high
purity can narrow profit margin and hurt honest suppliers.