By Doug Bartholomew, Contributing EditorAs more pharmaceutical manufacturers strive to improve the quality of their operations and product, corrective and preventive action (CAPA) software is becoming a more important tool.
The software is designed to help users respond to adverse events, which can range from a customer complaint about a given product, to raw ingredient non-conformance on the production floor or receiving dock, to an FDA warning, explains Tom Trahan, principal with Trahan Associates (Rosemont, Ill.). This relatively new breed of application software captures data and allows companies to evaluate the information and develop corrective action plans. The best systems, whether database- or process-driven, offer rigorous traceability and documentation as well as visibility throughout the organization.
In the relatively short time that CAPA systems have been around, they've forced individual facilities and whole companies to automate systems and processes that had previously been handled manually. Now available in comprehensive product suites encompassing change control, audit management and supplier compliance, CAPA systems can now be used to track documents, foster fail-safe workflow processes, and enable quicker, more certain resolution of errors or unusual production issues.
Instead of standalone CAPA systems, more companies now require linkages with change-control, SOPs and site audit management software, Trahan says. The software is also proving important in analyzing trends, allowing companies to take preventive actions.
No longer limited to the QA/QC silo, CAPA systems are also commingling with broader corporate information systems. The next stage will be linking them to enterprise resource planning (ERP) systems. "At this point, most manufacturers aren't there yet," says John McLaughlin, principal consultant at Taratec Development Corp. (Chicago). "But in the future, they're likely to demand that their CAPA systems share data with ERP."
"They'll want to set up automatic monitors that trigger certain processes, automatically, when some threshold value is reached," adds Trahan.
Quality Improvement Still Driving Force
Quality improvement is still the key driver for installing a CAPA system. At Bristol Myers Squibb (BMS), for example, the company's Flow Path system ensures that employees follow up on errors or quality issues more promptly than they'd been able to do with paper-based processes. The system maintains "follow-up" metrics that employees can meet or exceed, explains Susan Kenney, manager of lot release documentation, quality assurance systems, and training, based in Garden City, N.Y.
"With our new system, we created an automatic metric to work toward for both minor and major errors," she says. The CAPA system requires employees to record errors by category, product, and lot number, allowing for automatic trending. "There is no way to know that a trend is occurring with a manual system," she says. Trending also gets management involved, Kenney says. "They can watch the flow of each product and see the trends online."
BMS is also using CAPA software to track how each product was developed and produced, and to manage all supporting paperwork. "Our site director felt that the documentation associated with the product was just as important as the product quality or getting the product out the door."
Developed with the software vendor, Invistics (Atlanta), the company's CAPA software works hand in hand with its inventory tracking system. "Invistics developed a front-end piece for us that shows a web page for each shop order, so that anyone using the system could see where we were," Kenney points out.
"We can instantly see whether we are on time, behind, or late with the order." Before installing this system, she says, employees used paperwork to keep up with each shop order, a cumbersome process at best. BMS also uses the system to track the status of process changes. "After installing the CAPA system, BMS had 32 consecutive months of on-time product delivery," Kenney says.
She believes that an effective CAPA system is a necessity for a smooth operation. "I'm amazed at the number of pharmaceutical companies that don't want to take the time to automate their systems," she says. "My sense is that the industry is just not moving fast enough."
User Base Extends Beyond QA
Watson Pharmaceuticals, a $1.5-billion maker of branded and generic drugs, is also a believer. "CAPA is essential should anything ever occur out of the ordinary," says Phil Lofty, manager of computer systems for corporate quality assurance at the Corona, Calif.-based firm. "You need to keep track of the information and you want to be very timely," he says. A built-in timer alerts users to deadlines, so that action items can't sit in anyone's virtual inbox for too long. "This CAPA system reduces our cycle time for making the corrections," he says.
Watson had been using a CAPA system from Sparta Systems (Holmdel, N.J.) at one plant and decided to expand its use throughout the company's operations. "This electronic-based system enabled us to work through our various site-based differences, so that we were able to roll it across all sites," Lofty says. "With electronic signatures, we don't have to track down paper related to quality issues anymore. We've gained a considerable amount of time not having to track paper."
The web-based system has proved a boon to management, too, he says, since they can monitor the progress of quality-oriented fixes. "It gives management a tool to see how long it takes to make a correction at a particular site," Lofty says. "We use the CAPA system broadly, for any corrective action."
Although the corporate business owner of the Watson system is the quality assurance group, the use of CAPA is so broad that one-third of its employees take advantage of it. This includes staff in manufacturing, engineering, and research and development.
Closing the Loop on Follow Up
The lifeblood of any CAPA system is accurate and current plant-level data. If, for instance, a chemist runs a test in the lab and comes up with an out-of-tolerance result, he must fill out an electronic form that sets in motion a series of follow-up actions. "As part of this workflow, a series of checks and balances must be performed in the lab, and a corrective action must take place," Watson Pharmaceuticals' Lofty explains.
All of this data is entered into the CAPA system, so that a complete record is on hand of what was done to fix the initial problem and to ensure that it doesn't repeat. "Part of the workflow is to make sure that we circle back and find out the root cause of the problem, and then take preventive action to change the process," Lofty points out. "Also, the prevention aspect is on a timetable to verify that the necessary training is done for the changed process within 30 days."
In some cases, the corrective action might consist of a physical repair or change of some kind, such as installing a metal guard to ensure that the operator doesn't bump into something when performing a certain step in the process. The key benefit of CAPA is that it forces any company to make sure a follow-up action has been taken to correct the issue and take steps to prevent it from happening again. With manual, paper-based systems, such follow-up tended to take place later, or not at all.
Watson Pharmaceuticals' CAPA system has worked so well, in fact, that the company now is considering using it for other issues, like tracking workflow changes. "The system is flexible enough to accommodate our manufacturing procedures and policies, too," Lofty says.
C Is Also for Continuous?
At Cardinal Health, use of CAPA systems has been directly related to continuous improvement in pharmaceutical manufacturing, says Joseph White, a consultant recently retired from Cardinal, where he served as senior vice president for quality at the company's Pharmaceutical Technology & Services unit in Somerset, N.J.
He was responsible for quality systems at the company's various contract manufacturing operations producing softgel tablets, rapid dispersal formulations, hard-shell capsules and sterile products.
One of White's chief accomplishments was installing an enterprise-wide CAPA system at the company's 40 plants. "We wanted to integrate our operations around common standards, and we needed a software system to track our operational processes, control documents, and manage training in the manufacturing area," says White, who now lives in Hilton Head, S.C. "This was a business-driven project with information technology and quality as co-partners."
A problem presenting both business and technology issues for the company was the array of disparate document control systems in use at its various plants. Using Sparta's Trackwise system to monitor the flow of documents, the company was able to more effectively get its arms around the CAPA process. "Trackwise enables the company to trend and track change controls, corrective and preventive actions, out of specification items, deviations, validation reports and calibrations."
Cardinal expects to see greater productivity, and less wasted effort, as a result of its CAPA system. "Long term, we felt it would enable us to reduce headcount associated with this work as well as to improve our manufacturing quality," White adds. "There are significant time savings as a result of having an effective way to electronically track trends of what occurs in the plant."
To ensure the project's success, White made certain that the project management team had wide representation from the various units affected. "We had guidance and advice from each of the businesses," he recalls.
...as Well as for Compliance
Of course, one major reason for having a CAPA system is to improve regulatory compliance--so any CAPA system itself should be compliant with the 21 CFR Part 11 regulations.
When Bausch & Lomb (Rochester, N.Y.), a manufacturer of generic and proprietary ophthalmic pharmaceuticals, went looking for a CAPA software package, the ability to manage electronic signatures, time-stamped audit trials and maintain proper security per Part 11 requirements was near the top of their shopping list.
The system would also have to be manageable, both locally and globally, so that data could be shared among multiple plants and facilities. In addition, it would have to serve as a database for all facilities' CAPA information so that QA could be monitored globally. Ultimately, the company implemented CATSWeb from AssurX (Morgan Hill, Calif.) across its 40 plants worldwide, where it replaces a hodgepodge of paper-based and homegrown systems, as well as other software packages.
"Regulatory agencies are disappointed if they go into a plant and see major deviations that haven't been closed out in the last year," adds Cardinal Health's White. After all, as BSM's Kenney puts it, "When the FDA starts holding you accountable, they are not going to view your Microsoft Word documents as being either safe or controllable enough."
|Satisfying FDA, Improving ROI |
In January, 2001, a major pharmaceutical manufacturer faced a dilemma. The company had been issued FDA warnings for GMP and CAPA problems at one of its sites. At the time, the division's change-control systems were managed by gathering data electronically, then processing them manually, routing materials in paper folders to stakeholders for review and approval.
The CAPA system was designed with little flexibility, and change had to occur quickly to meet the changing needs of the operation. The company needed to ensure that any new system could manage the volume of changes expected to be processed and be flexible to allow for process changes, while meeting compliance standards.
At the time, the software that the division had built or bought to automate quality processes or manage documentation was generally made up of point solutions designed to solve specific problems and validated to a specific process. This approach led to inflexible tools that either couldn't be changed, or required time-consuming and costly development and revalidation.
Facing tight compliance deadlines, the company opted to build its own solution, and released ePAS (for electronic package approval system) that December, managing the product internally and developing it with the help of Trahan Associates (Rosemount, Ill). The solution included an administrative section for configuring all elements of the system, which meant updates to compliance processes, data fields and definitions, workflow, workflow rules, approver lists, approver groups and impact analysis forms were now all possible without programming and validation.
Implementing ePAS meant big changes for the operation's employees. Until then, all compliance documentation had been managed on paper. Now, employees would be managing these processes electronically. The implementation team cautiously rolled out the new system, choosing to add users slowly to lessen the impact of such a large change. Currently, over 2,000 people within the division use the platform to process compliance documentation for document changes, CAPA events, collecting defect data, approval processes, and reporting to management. The company has met FDA requirements.
In addition, according to the company, productivity has improved and savings have increased because the validated solution allows the company to make frequent changes through validated administrative functions, rather than through re-development and re-validation.
Prior to ePAS, estimates one company IT program manager, the savings required to meet the ROI hurdle for automating any quality process was $300,000 to $1 million, given the costs of developing, validating, training and implementing a solution. With ePAS, that hurdle has dropped to between $5,000 and $20,000. And where, in the past, the program manager might have tackled one or two processes per year, since going live with ePAS in December of 2001, he has automated 28 processes and plans to automate 17 more this year.
Server Solution Combines Advantages of Purchased and Hosted CAPA Apps
CAPA systems may save in improved quality and reduced errors, but enterprise systems can be costly. At March's Interphex conference, EtQ, Inc. (Farmingdale, N.Y.) formally introduced a new "Compliance Server" option for its Quality Management Suite.
An alternative to buying and installing an enterprise system, or relying on a hosted application solution, the compliance server is located onsite, using software that is maintained remotely by the supplier, explains EtQ's marketing director Tim Lozier. This eliminates the need for software administration, he says.
Costs start at $1,199 per month, he says, half the cost of running typical enterprise software systems, and the option offers a safer alternative to hosted solutions, in which critical documents and data are transferred over the Internet. The Compliance Server allows information to remain within the customer's network, and, because it operates independently of bandwidth, Lozier says, it eliminates the need for a separate dedicated connection.