During tough economic times, companies in most industries tend to look inward-focusing on perfecting core competencies and ensuring that they are operating as efficiently and cost-effectively as possible. When the economic picture improves, they are then well-positioned to move forward with new product ideas and investments in new resources, whether that's additional staff, advanced equipment or new business partnerships or acquisitions.
This was the trend that unfolded in the medical device industry in recent years, said Jay Wigley, medical programs manager for Alexandria, VA-based Analex Corp., a custom software developer. During the past few years, he pointed out, medical manufacturers have examined the fundamentals of process validation to make sure they've answered all the basic questions correctly for their company. Moreover, they have reviewed the key attributes of their products and how they can measure those qualities. Using traditional tools of statistical process control, many medical OEMs worked to improve those qualities or looked at them in new ways.
"In bad times, companies focus on doing the basic things well," Wigley said. "They re-examine their products and processes and process validations. That's a good thing since almost always some fundamentals have been overlooked."
Overlooking the fundamentals can prove costly. This past January, the Global Harmonization Task Force (GHTF) released its final document "Quality Management Systems- Process Validation Guidance." The report said that process validation is much more than a regulatory requirement-rather, it offers great business opportunities to OEMs and contract manufacturers.
The report noted: "While the completion of process validation is a regulatory requirement, a manufacturer may decide to validate a process to improve overall quality, eliminate scrap, reduce costs, improve customer satisfaction or [for] other reasons. Coupled with properly controlled design and development activities, a validated process may well result in a reduced time to market for new products."
Business benefits aside, OEMs and contract manufacturers would be wise to pay close attention to their process validations simply because regulations are becoming more complex, and the FDA is becoming more stringent in its enforcement.
"The FDA laws don't change often, but the policies on how the FDA interprets the laws or how it conducts its inspections do change constantly," warned Alan Schwartz, a consultant with mdi Consultants, Inc. in Great Neck, NY.
Schwartz, who has worked at the FDA, said medical device companies must keep up with current policies to ensure continued compliance. Doing so, he added, is no small task. That's one reason why many small companies, in particular, often seek outside expertise when performing process validation. Increasingly, larger companies, too, are asking consultants for help to better understand what the FDA wants and expects from their operations in this area. Certainly, companies want to manufacture the highest quality devices and meet regulatory standards, but there is also a costly penalty when the process falls short.
"The FDA is issuing more civil penalties and injunctions for failure to validate processes properly. Companies will be surprised to see that more and more warning letters are being sent, and the FDA is going after those companies that fail to comply," Schwartz said.
Therefore, ensuring quality and regulatory affairs staffers stay current on all regulatory requirements and hiring outside help when called for are becoming increasingly important in the medical arena. Fortunately in recent years, the FDA and the medical device industry have developed a cooperative working relationship.
"The FDA has become more of a business partner in terms of letting medical manufacturers know what is expected of them earlier in the device development process, and in providing clearer definitions of what it is looking for in process validation. Therefore, there are fewer surprises later," said Gregg Mosley, president of medical device testing lab Biotest Laboratories, Inc. in Minneapolis.
What to Validate
To steer clear of regulatory validation problems, more manufacturers today are developing standard operating procedures on getting devices from concept to the market place.
"Since the life cycle for many products today is so short-from two to three years-companies are striving to expedite process validation. By establishing good controls and good review processes, and knowing when to validate versus verify a process, manufacturers can get products to market faster," Mosley said. "You're also seeing a trend of innovative smaller companies partnering with larger companies with established processes, and companies that are growing rapidly through acquisitions hiring outside consultants to help them validate processes in an efficient, timely manner."
GHTF offered a process validation decision tree in its January 2004 report to aid manufacturers on determining when to validate versus verify or redesign a product or process. The report noted certain processes must be validated, including those involving sterilization, cleanroom ambient conditions and aseptic filling processes. It stated that manual cutting processes and visual inspections of printed circuit boards may simply be verified.
The report also advised manufacturers to create a master validation plan that notes the "processes to be validated, the schedule for validations, interrelationships between processes requiring validation and timing for revalidations."
"It is extremely important that manufacturers have well-established standard operating procedures (SOPs) in place for design and validating processes," noted John Hendrick, executive vice president of the worldwide medical division of electronics contract manufacturer Sanmina-SCI in San Jose, CA. He pointed out that today's devices often combine technologies, which requires manufacturers to carefully validate their processes and even revalidate processes they've used in the past.
Because many of these products combine technologies not traditionally found in a single product-disposable properties with electronic capabilities, for example-the FDA is likely to pay particular attention to a manufacturer's processes when evaluating the new device's safety.
"Without question, every new product must be revalidated. Validation protocols, test reports and recommendations based on test results are necessary for every process and product-even those of second-, third- and fourth-generation products," Hendrick emphasized.
A Better Process
While process validation techniques themselves-including sampling size, design of experiment, etc.-haven't changed, there have been significant shifts in how companies analyze the resulting data and the scope of process validation.
"The biggest trend I've seen recently is better use of and integration of process validation with risk management," said Ken Fine, president of Proven Process Medical Devices in East Walpole, MA, a provider of design, development, validation and manufacturing services. "Today we coordinate and identify the goals of process validation in conjunction with our risk management model more than we did in the past. Products that present more risk see a more rigorous process validation. When we evaluate process capability studies, Six Sigma comes into play, and we assign a level of three to six, depending on criticality. We're also applying design of experiments more than in the past to better understand and optimize the process control parameters as a function of the process risk."
Risk management affects process revalidation also. Products and processes that are associated with more risk are re-evaluated more often than their less risky counterparts.
"Risk management is becoming a huge issue and impacting everything," said Brent Noblitt, senior partner at consulting firm Noblitt & Rueland in Irvine, CA. He noted that not only are manufacturers examining which processes or products can potentially pose a hazard to users or patients, they are also considering where they invest their resources and time.
"A more risky process-one that presents a hazard or consumes a lot of resources-requires more in-depth consideration than less risky processes," Noblitt said. "The FDA also is starting to position regulations in terms of risk."
Noblitt pointed to a second trend being embraced by the FDA: the global harmonization of standards. The FDA is working more closely with other countries so that its guidance and regulations will be complementary. Recently, in the Federal Register, the FDA announced the availability of and requested comments from the industry on several GHTF documents, including the final process validation guidance and the risk management draft guidance.
Automation software is increasingly playing a role in process validation. First, there has been a shift from paper to online records, which saves manufacturers storage space as well as streamlines the record-keeping process. Because process documentation must reflect all changes made with accompanying approval and signatures of team members before a product moves to the next phase of the production cycle, a significant amount of time can be spent chasing down team members to sign off on changes. Online records are instantly available to all team members, who can also see the latest version of the record as well as previous editions.
More importantly, software now is an integral part of many medical devices, and it controls many production steps. As a result, the FDA is carefully monitoring its use. CFR Part 11, which provides guidelines for validating software, continues to evolve. (The FDA is holding a public meeting June 11 in Washington, D.C., to discuss electronic records and electronic signatures.)
Manual systems are easier to validate than software, pointed out Roy Humphrey, product line manager for transitional manufacturing for contract manufacturer HEI, Inc., in Boulder, CO. He noted that new, extra requirements for software validation increase costs and may cause some outsourcing providers not to automate some processes as quickly.
Software has also refined process validation, giving manufacturers information they once thought unattainable.
"It used to be a great mystery to medical manufacturers as to how to control the variability of plastic parts in high-volume runs. Five or six years ago, attempting to validate a machine to reduce variability in the product was perceived as an insurmountable challenge," noted Analex's Wigley. "In the last nine months, at least two companies have created process control software for injection molding machines that monitors process sensors in real time for temperature, pressure, timing, sequencing of dropping of the tool, the vacuuming of the tool, etc. By examining the data, the user is able to determine quickly which factors are affecting the variability most, and the manufacturer can therefore adjust the process in real time rather than simply evaluating the final product."
A More Thorough Picture
Some manufacturers in the past may have developed records of processes through piece-meal efforts; today they are looking at a product's entire life cycle when validating processes. Proven Process Medical Devices has incorporated process validation into every stage of its products including design controls, process flow, design for manufacturability, design for testability-all the way through distribution.
HEI's Humphrey added that customer service has become a larger part of the equation as well. "Once you have your design and production processes validated, the focus should shift to 'How do I optimize my processes to provide the best customer service?' The answer is to apply Flow Manufacturing and Six Sigma tools, to apply statistical analysis to eliminate deviations from processes. The driving mantra today is 'How do you get rid of waste?'" Humphrey said.
More companies-large and small-are outsourcing process validation. Smaller companies understandably often don't have the internal resources to keep abreast of the rapidly changing regulatory environment, but even larger companies, especially those growing quickly, find that outside expertise in this area allows them to focus on their core competencies rather than on quality systems.
"Particularly in sterilization and package validation, we're seeing more and more people outsourcing the validation process itself," said Mosley. Manufacturers are hiring experts to write the protocols and final reports. Often these experts are the contract manufacturer or contract sterilizer companies, Mosley added.
They also are starting to realize that it is best to hire experts at the outset of conceptualizing a new product to ensure that process validation is accurate and thorough. "It's a challenge, sometimes, convincing OEMs to involve expert help up front," noted Hendrick. "Process validation should be addressed from phase one of design, not once the product has entered into the second or third phase."
Hendrick also advised medical OEMs to exercise caution when selecting a contract manufacturer. Not only should the contractor be able to meet the OEM's technical needs, it also should understand and be capable of meeting all FDA and ISO requirements for process validation and manufacturing.
"Many contract manufacturers still have the mentality of manufacturing for consumer products. The transition to a medical device mentality is a significant one," he said.
With the economy appearing to strengthen, medical manufacturers are poised to push more innovative devices out of the pipeline and reap the rewards. The focus on process validation fundamentals will have no small effect on that success.
"The process is what makes the product," Humphrey argued. "If a process is out of kilter, the product will be, too. Process validation ensures that products do what they're designed to do. No matter what business you're in, it makes good business sense to validate all of your processes since they dictate how well your product is manufactured. To succeed, you must validate."
About The Author
Stacey L. Bell is a Tampa, FL-based freelance writer who specializes in business and marketing issues.