|Ensuring FDA quality standards are met is a priority for all medical device manufacturers. A worker at a B. Braun plant checks documents on the plant floor. Photo courtesy of B. Braun OEM/Industrial Division.|
The creation of the Quality System Regulation (QSR) was born out of concerns about design controls of medical devices. More than eight years later, the regulation has become much more encompassing than its original scope.
“There is a much greater [quality] impetus that the FDA is putting on companies. There is no question about it,” said Robert Schiff, CEO and founder of West Caldwell, NJ-based Schiff & Company, a regulatory consulting firm. “They concentrate very heavily on quality.”
Quality systems today are required in just about every facility involved in medical device manufacturing, including those belonging to contract manufacturers.
To satisfy regulators, companies must design their systems to encompass a myriad of areas. These include important functions such as Corrective Action/Preventative Action (CAPA) programs, management review and production and process controls.
As the device industry became more sophisticated and the products themselves grew more complex in the past eight years, quality systems also grew in scale and complexity.
David Feigal, the former director of FDA’s Center for Devices and Radiological Health (CDRH) and current head of the medical device and biologics practice at NDA Partners in Falls Church, VA, said that quality systems today are more focused on industry-specific standards.
“We have the [ISO] 13485 standards in medical devices replacing the ISO 9000 family as a more device-specific set of standards. The standards include management controls more prominently,” said Feigal.
|When an OEM outsources manufacturing, in a sense it is also outsourcing its quality system. That’s why it must make sure that its contract manufacturers meet QSR requirements.|
In small or large doses, control has always been considered pivotal to a good quality system. And it is that concern, in part, that has pushed the evolution of QSR over the years. Before its 1996 introduction, the regulation was known as current Good Manufacturing Practices (cGMP). Back then, the FDA found that 52% of the recalls in the medical device industry were due to design control flaws.
To address these design problems, the introduction of QSR required domestic and foreign manufacturers to adopt a quality system for the design and production of medical devices.
“The design control requirement is essential to ensure that the design phase of the device does what it is supposed to do,” said Wally Pellerite, the assistant to the director of FDA’s Office of Compliance.
While design is often the focus for many companies, other critical elements in a top-quality system can sometimes be overlooked, according to Alan Schwartz, executive vice president of MDI Consultants in Great Neck, NY.
“The problem with CAPA is that most people are not using it right,” said Schwartz. “People are using it almost as an exercise and not doing continuous improvements and monitoring it….Most don’t even understand what a preventative action is, so that is a big problem for QA. The other thing is they are not doing the trend analysis…and not coming up with corrective or preventative actions.”
Medical device companies that boast a very good CAPA program are less likely to attract the attention of regulators, according to some consultants.
“They (FDA) generally look at the (CAPA) system and see if it is pretty much running in force,” said Judy Andrews, manager, quality and compliance services, at MDCI in North Attleboro, MA. “If they find one or two errors, they are certainly not going to write up a minor error if everything else is running in place. It’s finding the same thing over, over and over again that leads them to write something up.”
Companies that discover a flaw in their quality systems often fix the problem but do not look beyond it. “They might not go deeper to find the root cause to determine if there is a corrective action needed so it doesn’t happen again,” said Dennis Rubenacker, co-founder and senior partner at Noblitt and Rueland, a consulting firm in Irvine, CA. For instance, he said, fixing a non-conforming product but failing to implement preventative steps is a common mistake.
All the components in a quality system work in conjunction with each other.
While CAPA programs help companies to constantly identify shortcomings in their systems, they also must effectively manage data to identify problems in the process.
That’s why some consultants point out that document management plays an important role in any quality system.
“Control of records, making sure that all of the design history files, the risk management file, the complaint files and any device reporting” are key elements in document management programs, Andrews said. “All of those files need to be accessible, can be properly stored and can be retrieved in a fairly easy manner.”
Additionally, considerations such as risk management and software validation have also become prominent in quality programs.
“When they (FDA) walk in, one of the things that they want to look at is risk analysis, and five years ago, they did not do that,” Andrews added.
While quality programs are constantly improving and becoming more sophisticated, they still impose considerable challenges to medical device manufacturers.
One of the biggest hurdles is system and process validation.
“I think the main area is process validation, making sure all the processes that require validation have been validated,” said Schwartz. “If you look at most of the warning letters and most of the injunctions, they were based on validation or process validation.”
Part of the difficulty when it comes to validation stems from questions about regulations such as 21 CFR Part 11, FDA’s regulations on electronic records, “There seems to be a fair amount of confusion on that,” said Andrews.
When it comes to quality programs, there is a definite difference between large and small medical device companies. The FDA makes no bones about it. In fact, the QSR clearly states the distinction in the regulation:
“Typically, large manufacturers will have a quality system that exceeds the medical device QS regulation. Small manufacturers will typically have a proportionally simpler system. FDA recognizes that a small manufacturer may not need the same amount of documentation that a large manufacturer does in order to achieve a state-of-control; and that some of the records maintained to fulfill the GMP requirements for written procedures may not be as long and complex for a small manufacturer.”
“Their requirements go over and above what’s required” under QSR, Rubenacker said of larger manufacturers. “Whereas with a smaller company, they’re just trying to get their 510(k) cleared, either to be manufactured or to be sold to one of the bigger companies. They’re trying to put in a more efficient, lean quality system.”
Failing to adhere to QSR can be devastating to medical OEMs. Some recent instances showed that the FDA will impose the same heavy-handed toll on non-conforming manufacturers regardless of their size. Recent enforcement actions against Utah Medical and earlier against Abbott Labs are good examples of problems that can arise when the agency isn’t satisfied with a company’s quality system.
In August, the FDA asked the U.S. District Court in Utah to stop a medical device maker from manufacturing and distributing its products until problems with its cGMP were fixed.
Midvale, UT-based Utah Medical responded in court papers that the FDA unfairly tainted its reputation by making false claims about the safety of its products. Company officials have said that in prior discussions with the agency, they were led to believe that the company was progressing toward meeting regulators’ requirements.
Did the injunction against Utah Medical signal a tougher QSR stance being adopted by the FDA these days?
“I don’t think it (FDA’s position) has changed a whole lot except you will see these aberrations like Utah Medical that do not come along too often,” said David Link, executive vice president of Boston-based EXPERTech, a division of consulting firm Boston Healthcare. “Usually, if a company concludes that it really doesn’t understand what the FDA is expecting, the company can seek meetings with the FDA and have things straightened out. In this case that seems to have not happened.”
But even when a company seeks FDA input, it might still fail to satisfy quality requirements.
In the Abbott situation, the FDA and the Abbott Park, IL-based company battled over how to meet QSR standards at its Lake County, IL plant for more than four years. Earlier this year, the FDA finally found the company had conformed to the QSR and could begin manufacturing products again. This came only after the company agreed to make a $129 million payment as part of a consent decree.
“The FDA concluded that Abbott did not have the ability or refused to make the necessary changes,” said Link. “So the agency says, ‘Okay, one alternative is to serve them with an injunction,’ which they did, and it turned out to be costly to Abbott.”
Although the Utah Medical and Abbott examples highlight the troubles that a medical OEM can fall into with the FDA, the agency generally seems willing to work with medical device companies, some observers say.
“They used to show up at your door unannounced,” said Andrews. “Now, they will call you and tell you that they will be there in a few days. If you want to move it a day or two, they are pretty willing. They are certainly very open to working with you and open to conversation.”
FDA facility inspections are supposed to occur every two years, but because of past agency staffing shortages and growth in the industry, the average inspection now occurs every four years.
“The agency’s resources are limited,” Pellerite said. “More practically speaking, they (inspections) happen every four years. Those are routine inspections.”
“For cause” inspections, however, take place as needed. For instance, the FDA recently scheduled an inspection of Boston Scientific’s stent-making facility after defects in its products led to a widespread recall.
“If a firm is making a correction to a product or recalling a product, they have to inform the FDA of those device recalls or device corrections. We do have time set aside for ‘for-cause inspections’,” Pellerite added. “When we become aware of a problem with a product or a particular firm, we have built into our procedures [a plan for] setting up and conducting inspections that is outside of the normal work plan.”
Even when the FDA is made aware of a problem, the agency appears more willing to work with industry, some observers point out.
“They use to go in with an approach [of]…‘Let’s find out where they failed so we can nail them,’” said Rubenacker. “Now, the approach is: ‘They can have problems, but as long as the quality system fixes the problems with corrections, corrective actions, preventative actions, that’s good.’ So I think that philosophy has changed.”
Rubenacker noted that he saw an attitude change at the agency when David Kessler resigned as commissioner in 1997 after six years at the helm. More recently, Mark McClellan, before he was named administrator of the Center for Medicare and Medicaid (CMS), also embraced working more closely with industry. Acting commissioner Lester Crawford is currently in charge of the FDA until President Bush names a replacement.
When an OEM outsources manufacturing, in a sense it is also outsourcing its quality system. That’s why it must make sure that its contract manufacturers meet QSR requirements.
“Whether they are an OEM or a contract manufacturer, they still need to do their work according to QSR,” said Feigal. “However, they are less likely to get an FDA inspection than an OEM. The FDA would expect that as part of the OEM’s quality system, it ensures its contract-manufactured products are produced under QSR.”
For OEMs that outsource, routine audits of their partners are a must. Furthermore, CMs themselves must ensure their suppliers also conform to QSR. In some instance, contract manufacturers are asked to perform on-site inspection of their suppliers. As the medical device industry places a greater emphasis on quality, those requirements are being imposed on vendors.
“They (OEMs) are trying to cover all of their bases and trying to make sure you’re doing what you are supposed to do,” said Tom Corl, quality assurance manager at Specialized Medical Devices, a contract manufacturer based in Lancaster, PA. He added that some customers don’t care whether a vendor is certified in ISO 9001 or ISO 13485; they still must pass OEMs’ quality standards, including regular audits.
In some instances, CMs are expected to have a quality system even more comprehensive than the customer’s.
In other cases, CMs are asked to adapt their system to the requirements of a particular OEM.
In any case, OEMs now expect their vendors to meet whatever quality standards they mandate, and CMs have learned to be flexible in fulfilling those needs.
“We’ll modify and adopt what their requirement is and add it to the system as long as we are capable of doing it and it makes sense for us,” said Corl.
As the industry becomes increasingly international, quality systems will have to adapt to changes brought about by globalization.
Third-party inspections, for example, bring the industry a step closer to global harmonization as companies in the future adhere to possibly one global quality standard accepted by a number of regulatory bodies. In those instances, ISO standards may play an important role.
The use of outside auditors may become more common now that the FDA has trained the first group of third-party participants earlier this year. They are expected to slowly replace FDA staffers in some audit programs.
Furthermore, as Feigal pointed out, there may be tiers of quality as well. “One system is for the countries that assess quality as part of their commerce activities; for example the CE mark, as opposed to the other system for countries that also have enforcement responsibilities,” said Feigal. “The former does not require documentation that the latter requires for legal actions. A commerce-oriented system leaves recalls to the companies, while a country with enforcement may have recall authority itself.”
Regardless of how global quality standards change, one thing is for sure: there is no going backwards so medical device manufacturers should expect tougher requirements ahead.
At the same time, aided by a market full of tools, knowledgeable vendors and a less adversarial FDA, medical device manufacturers can also expect to find plenty of help in their efforts to perfect their quality systems.