Put to the Test
Contract test laboratories adjust to requests for more device testing, details from the FDA.
Tim Sohn, Associate Editor
A NAMSA employee analyzes data from a high-performance liquid chromatography instrument. One way medical device testing providers are keeping up with the medtech technology curve is by serving on International Organization for Standardization committees. Photo courtesy of NAMSA.
Medical device contract testing laboratories are receiving increased requests from OEMs for regulatory support, industry experts told Medical Product Outsourcing.
The trend can be attributed to the U.S. Food and Drug Administration (FDA) using a more cautious approach in the medical device approval process after agency scientists said last winter that the process was flawed. Some experts claim that the agency’s new product reviewers are less experienced in certain aspects of testing.
Pat Nolan, chief operating officer at Eden Prairie, Minn.-based DDL Inc., a provider of medical device product, package and material validation testing, said his company has noticed that new FDA reviewers are not as technically informed about the requirements and testing techniques used for medical device package compliance. As a result, the auditors often request much more documentation in the form of testing worksheets, data and test reports from the medical device manufacturers (MDMs). He noted also that as a result, DDL is spending an increasing amount of consulting time with the MDM’s technical and quality staffs to explain how their company should comply with ISO (International Organization for Standardization) standards and regulations.
DDL is expert in interpreting the ISO 11607 standard, which specifies requirements and test methods for materials, preformed sterile barrier systems, sterile barrier systems and packing systems that maintain sterility of terminally sterilized medical devices until they are used.
Nolan isn’t only seeing a staff turnaround at the FDA. He’s also seeing this trend at OEMs. “The experienced packaging guys are moving on to other companies or leaving the industry. They are leaving huge gaps in terms of that intellectual knowledge, and often times the packaging process is left to other engineering staff with little knowledge of package design and validation,” he said.
Robert Mosenkis, president of CITECH, a company in Plymouth Meeting, Pa., that offers mechanical and electrical testing, has had similar experiences with neophyte FDA reviewers. In particular, Mosenkis has noticed that new reviewers are not too familiar with electrosurgical accessories, devices that his company tests often.
In the past, the FDA generally always had accepted CITECH’s electrosurgical accessories testing. Not anymore. “What they are doing is taking parts of the standard that apply to the electrosurgical generator, and are saying, we want you to do it with your accessories connected to several different generators. We have tried to argue that the test that they’re asking for is 100 percent dependent on the generator. It will not make a difference what accessory you plug into it. We tell this to the client, and the client can make no headway with FDA,” Mosenkis said.
Terry Langenderfer, director of global marketing for Northwood, Ohio-headquartered NAMSA Inc., which offers medical device pre-clinical testing services and clinical trials management, thinks it’s too early to determine the changes that will take place under the new administration at FDA and its Center for Devices and Radiological Health. However, he believes there is an industry perception that the agency is taking a more conservative approach in its device reviews.
He said NAMSA occasionally meets with the FDA on behalf of and independently of client engagements. “To share the approach and the strategies with the FDA sooner can often help ensure that your submission moves more rapidly through the agency because they’re familiar with what you’re doing and understand what you’re doing from the outset,” said Langenderfer, adding that his firm stays on top of regulations by serving on ISO working groups that create and maintain ISO standards.
The slow pace of change at various regulatory agencies, however, has not stopped OEMs from asking for quicker turnaround times for testing.
The Time is Now
Donald Palme II, Ph.D., vice president and chief scientist at St. Paul., Minn.-based WuXi AppTec, said speed helps device OEMs generate more revenue. “I have worked for companies ranging from the very large medical device companies to start-up where I was the first employee. When you look at the pre-clinical testing arena, just for the safety testing component alone, this can take up to three months to complete the testing. This costs companies not only money for the testing but also delays for the regulatory submissions which amount to millions of dollars of lost opportunity. Planning is everything, and companies need to work with a responsive outsourcing partner.”
WuXi AppTec is a global medical device and biopharmaceutical outsourcing firm with operations in China and the United States.
One thing that needs to be kept in mind for pre-clinical safety testing, according to Palme, is that most testing has very defined guidelines. “If you’re doing a GP sensitization test, it’s 28 days on test. I can’t shorten that. Or if you have to do a 90-day implant, that’s 90 days on test. There’s no one who can figure out how to do a 90-day implant test in 60 days,” he said.
Brandon Tillman, sales manager at Salt Lake City, Utah-based Nelson Laboratories, which provides full life cycle microbiology services for the medical device, pharmaceutical and dietary supplement industries, said that time becomes a critical issue because most testing is done shortly before a device is presented to the FDA for approval.
“Usually, where we come into the process, unfortunately, is toward the end. What happens is, even if you’re a large company, usually you work out the design, you make sure it works, you make sure you have the market, you make sure you’re going to make money off of it. And then the very last thing is, oh yeah, by the way, you have to do all this regulatory testing so that the FDA approves it. For that reason, people want us to complete their testing yesterday because we’re the last thing they need to do in order to get to market,” he said.
Tillman said his company monitors timelines closely. Such a focus on lead times led the company to create a new position—director of continuous improvement and Lean manufacturing—in an effort to reduce lead times for clients.
Strategically Minimizing Testing Saves Cost and Time
While OEMs want results faster from testing providers, they also are constantly looking to reduce the amount of testing.
Jim Rancourt, Ph.D., founder and CEO of Polymer Solutions Incorporated, cited two factors for the desire to minimize testing :“Cost and time. Of course there is risk associated with each. Release testing
A Nelson Laboratories study director performs a gravimetric analysis measuring the weight of the extracted residue. This is part of the residual manufacturing material test analyzing device cleanliness. Photo courtesy of Nelson Laboratories.
lot size must be carefully assessed to ensure the safety of the product. And the time it takes to develop robust release testing methodologies can require extensive testing. The earlier involvement in product development by the lab testing facility, the less risk for unmet timelines and higher than expected costs.”
Based in Blacksburg, Va., Polymer Solutions offers customers chemical analysis, physical testing and molecular analysis.
Tillman also sees a trend to minimize testing. He said his company tries to closely partner with clients and understand their goals, offering advice in the early stages of the product development process. “And really if at the beginning you think of the regulatory aspects that you’re going to have to encounter, usually it goes quick and smooth, and it’s not that expensive,” adding that it is much more expensive to try to fix things at the end of the process.
Medical device OEMs also are continually looking to reduce in-vivo models, said Langenderfer. “That is something that has been occurring for quite some time. One of the challenges in replacing or providing an alternative assay is the time it takes for it to be included in a consensus standard and adopted by the medical device industry. But, yes, there is still a strong desire for organizations to reduce the number of animals used with in-vivo models, replace specific models with a species that’s lower on the phylogenic scale, and potentially supplement or replace in-vivo models with in-vitro assays,” he said. One way that NAMSA has addressed this issue was by acquiring CeeTox, a contract research organization that is focused solely on developing in-vitro toxicity screening assays, in 2005. “We’re in the process now of commercializing some of that technology into our industry, which is medical device,” said Langenderfer.
Palme said ISO 10993-2 speaks specifically to the reduction of the use of animals in testing. Switching from in-vivo to an in-vitro model would be ideal because it eliminates the cost of maintaining a facility with animals, Palme noted. “You’ve got everything from storage of feed all the way up to the cost of your staff and facilities, and that can be extremely expensive. So, it’s a revenue saver, it’s a regulatory saver, plus you get an independent review on it,” he said. But in today’s regulatory environment in-vivo testing is still required.
A risk assessment can be used when trying to decide whether to use in-vitro or in-vivo testing, Palme added. Risk assessments are more commonly accepted in Europe, he claimed, “but it is coming on here [in the United States] also, and it is definitely an option to performing in-vivo tests. It doesn’t mean it’s cheaper or faster, but it is an option to reduce the use of animals in testing.”
One advantage of performing a risk assessment is the possible reduction in animal testing. However, there is the possibility that the FDA will not accept a risk assessment because it has not accepted Part 18 of ISO 10993, a component of the risk assessment analysis, Palme said, adding it should be approached as a scientific way to justify which studies do and do not need to be performed.
Despite the drive to minimize testing, there are definite advantages to outsourcing testing services to contract laboratories, including cost, laboratory personnel and regulatory knowledge.
“To run an environmental chamber really takes a lot of expertise to keep those machines running and to be able to make them efficient as possible,” Nolan said, adding that his company doesn’t require the OEM to do more than required by regulatory agencies.
Mosenkis said, “Many smaller companies that make the electrosurgical accessories generally are experienced in metal and plastic fabrication. They really don’t know high-frequency electricity, and they have absolutely no capability and no idea how tests are to be done. They just have nobody in house.”
He and other industry experts pointed out that having an independent laboratory conduct testing eliminates a conflict of interest. “Other companies just feel that it [testing] should not be done by the same people who are involved in building the product or designing it. They’re just looking for a fresh set of eyes,” Mosenkis said. “Our focus is on testing; their focus is on the product development.”
Kevin Knight, president of Knight Mechanical Testing LLC, a mechanical testing lab in Fort Wayne, Ind., said the benefits of outsourcing vary depending on the size of the OEM. Large medical device manufacturers, most of whom already have in-house testing facilities, use outside testing services to handle overflow work during periods of high demand.
Outsourcing testing to contract labs also is more cost-effective for the start-up or small OEM. “A lot of them [customers] are surgeon inventors who are very familiar with the function, the purpose of their device, but maybe not so familiar with the ASTM and ISO standards that their device must be tested to for the submission, as well as the acceptance criteria with regards to the testing…So, it really comes down to the equipment, the service they get and the experience,” Knight said.
ASTM International, or the American Society for Testing and Materials, publishes standards, specification documents, test methods, classifications, practices and guides describing the characteristics of materials, systems, products and services.
Keeping Up With the Curve
Industry experts say that there is a link between keeping up with international and FDA standards and the medtech curve.
Keeping up with technology can certainly be difficult. Tillman said his firm stays on the cutting edge by participating in standards committees for ASTM. “Because the industry is regulatory driven, the standards committees are the tipping point, the edge of the spear of what is going to change.”
Mosenkis and Rancourt have had an easier time keeping up with the curve.
“We tend to operate sort of on the back end of it. We don’t deal with the high-tech stuff. So, we don’t face that problem,” said Mosenkis. “Basically, our scientists are trained in fundamental foundational principles of polymer science. Because we have worked for such a wide range of clients over the years, we can take on each new type of challenge as it comes along,” said Rancourt.
Technology and Techniques
New technology and techniques usually aren’t problematic for testing providers as long as they stay on top of what’s new in the medical device technology world.
Tillman said Nelson Laboratories offers residual material manufacturing testing, used for stainless steel or titanium implants, where those devices are cut or manufactured. Such testing is used to ensure there is no excess oil left on implants; any residual material can result in the rejection of an implant.
Palme said his company is developing new testing and techniques on a daily basis through its customs program. “We sit down with the client and look at what they’re trying to achieve that’s different from standard biocompatibility testing and develop a program individual to them. It may be a custom test, where we have to research, look at academic materials, develop the test and method, validate it and then offer it to the client. It may be something that’s only done once, and we never do it again,” he said.
Knight noted that test labs must be adept at capturing data from tests. “You want to keep up with the latest electronics and software from your equipment and manufacturers. With respect to some of the new devices, you’re always looking for different ways to test different devices. You’re looking at different types of equipment and different ways to apply load,” he said. Many times, Knight added, labs must modify past standards to meet the motion or function of new devices.
The Future of Testing
Testing providers don’t see any slowdown in the future for testing requests.
“I think at least as of late, we’ve seen a push for more testing from the FDA and in some cases a break away from the standard testing that’s been required in the past. I think we’ll see an increase in the amount of testing required because a lot of these devices are different than anything else that’s out there,” Knight said.
Palme thinks there will be a heavier reliance on ASTM-type testing methods, which are constantly being evaluated and revised. He envisions the FDA moving away from guidance documents, which reflect the agency’s current thinking on a topic, and relying more on outside sources for validated and non-validated testing methods. Palme also predicts that customers will request more custom testing.
Tillman doesn’t see many changes coming soon from the FDA. “Regulatorywise in the FDA, it’s pretty slow moving, and there’s isn’t a lot of change associated with it unless there’s some dramatic thing that happens.” Tillman, however, has noticed medical devices being combined with pharmaceuticals, as well as more requests for regulatory consulting services.
Medical device contract testing laboratories are responding to changes at the FDA, including new reviewers and a more cautious approach to medical device approvals after reports surfaced of flaws in the process. Labs are reporting that the agency is working closer with testing providers, sometimes requiring more or less testing, or asking for the rationale for certain tests. OEMs want faster turnaround times, which can trim costs, according to industry experts. In addition, some medical device manufacturers are keeping up with the medtech technology curve by serving on standards committees.
Clearing Up the ISOs
Industry experts believe contract testing laboratories should follow ISO 17025 at a minimum. However, there often is confusion between that regulation and quality management system standard ISO 9001.
Here are definitions of the two standards:
ISO 17025 specifies general requirements for the competence to carry out tests and/or calibrations, including sampling. It covers testing and calibration performed using standard methods, non-standard methods and laboratory-developed methods.
ISO 9001 specifies requirements for a quality management system where an organization needs to demonstrate its ability to consistently provide products that meet customer and applicable regulatory requirements. It also aims to enhance customer satisfaction through the effective application of the system, including processes for continual improvement of the system and the assurance of conformity to customer and applicable regulatory requirements.