Mark Crawford, Contributing Writer09.19.18
Thanks to the increasing complexity and miniaturization of medical devices, coupled with evolving manufacturing technologies, new materials, and more stringent regulations, medical device testing and analysis is booming.
There is more to examine in an orthopedic product than ever before. Regulators expect higher-resolution testing of polymeric materials for low molecular weight impurities and additives such as residual monomers and solvents, antioxidants, and light stabilizers. More detailed material compatibility (limits of reuse) and device cleaning studies are often required for 510(k) submissions. And it’s not just devices that need testing—packaging is also under considerable scrutiny, including its usability and impact to the environment.
As a result, testing and analysis in the medical device industry is on the verge of dramatic change. Many standards are being rewritten, with regulatory bodies more willing to accept new analytical techniques. Regulators are also developing a deeper understanding of the complexities of chemistry testing for toxicological risk assessment and biocompatibility, which will likely lead to more scrutiny of analytical methods. Testing laboratories, therefore, must be at the top of their game.
“If you did testing just a year ago, the current requirements might surprise you,” said Thor Rollins, director of extractables and leachables (E&L) consulting for Nelson Laboratories, a Salt Lake City, Utah-based medical device testing laboratory.
The U.S. Food and Drug Administration (FDA) continues to push medical device manufacturers (MDMs) and their supply chain partners to build risk evaluation into every step of the medical device design process. This includes selecting safe raw materials, working with reputable vendors, and using the most suitable manufacturing and sterilization processes.
“Such risk-based planning not only helps develop safer devices, but also identify any required testing,” said Chris Parker, associate department head for Toxikon, a Bedford, Mass.-based provider of in vivo, in-vitro, and analytical testing services for the medical device industry. “Analytical chemistry evaluation, such as E&L, is becoming more of a requirement as it provides data for toxicological evaluation. Biocompatibility and functional evaluation testing is also becoming more important globally, with international initiatives such as the Medical Device Directive in Europe.”
Because of these influences, the medical device validation industry is now running at its highest level in the past decade. “Deregulation, corporate and individual tax cuts by the Trump administration, and the restructuring of the FDA have all played a vital role in this recovery,” said Gary J. Socola, president of Rochester, N.Y.-based HIGHPOWER Validation Testing and Lab Services, a provider of reusable medical device cleaning, packaging, and sterilization validation services. “It’s an exciting time for OEM device manufacturers, their suppliers, and service providers.”
Testing and Analysis Trends
Today, medical device testing is all about risk assessment. Medical devices are becoming more complex and are often made from new materials with unique engineered properties. Device designers, however, also use traditional materials and processing when they can, or combine these materials and methods with more advanced technologies.
“Because of these extremes, the traditional testing that was established decades ago just doesn’t make the cut anymore,” said Rollins. “This is why we now rely on risk assessment as the first step to safety, then develop a testing plan that is unique to the inherent risks of that device. The benefit of this approach is increased safety, often accompanied by a decrease in testing.”
With testing equipment becoming more sensitive, risk assessment can be taken even further. For example, because they can now be measured with precision, there is more emphasis on identifying low-level impurities or other compounds that could impact performance or safety. Liquid chromatography-mass spectrometry (LC-MS) plays an important role in the analysis of organic chemical components of medical devices and other products, including low levels of impurities in raw materials, degradation products, contaminants, or chemical elements that may be present in medical devices and other products.
E&L testing—looking for impurities and additives that could migrate out of a medical device into surrounding tissue or bodily fluids—is becoming increasingly important as part of a comprehensive safety evaluation mandated by the FDA and other regulatory bodies. “Manufacturers of bio-absorbable medical implants are expected now to provide data to the FDA characterizing the by-products generated as a result of breakdown of the polymer in the body,” said Jason Todd, chromatography laboratory manager for SGS Polymer Solutions, a Christiansburg, Va.-based provider of chemical analysis and physical testing of medical devices, pharmaceutical products, and other industrial products.
“These methods can also be used to determine the absence or presence of intentional taggants to deter the use of counterfeit polymers and products,” added James Rancourt, technical director for SGS Polymer Solutions.
As more MDMs utilize electronics and embed sensing technologies into their medical devices, especially orthopedic products, there is greater need to test these functions. For example, force and pressure contact and distribution are important variables in nearly any orthopedic treatment segment. “Whether the purpose is to quantifiably assess an individual’s foot function or gait, or understand how contact surfaces of articulating bones and replacement limbs are functioning or loading, the ability to map pressure distribution presents endless opportunities to enhance orthopedic testing and analysis,” stated Mark Lowe, vice president of sensors for Tekscan, a Boston, Mass.-based manufacturer of ultra-thin tactile force and pressure sensors to optimize medical product design. “Not only are these sensors thin, flexible, and customizable for capturing force in specific spaces, they can operate on simple electronics, which improves power efficiency.”
Implementation of FDA rules for unique device identifiers (UDI) on medical devices has resulted in a surge of testing for UDIs. When the UDI system is fully implemented, labels on most devices will include a unique device identifier in human and machine-readable form. During the design control process, many OEMs are testing their reusable devices not only in their FDA-cleared sterilization process, but also their disinfection process. “This makes sense, as this is how the device is used in an actual clinical setting,” said Socola. “We have seen UDIs that were fine when exposed to a sterilization process but became unreadable when the disinfection process was added prior to sterilization. With the various alkaline and other detergents now available in healthcare, disinfection steps should not be over looked when OEMs are performing durability testing on devices with UDI laser etching or imprints.”
What OEMs Want
Risk mitigation is a top priority for OEMs. They want more thorough testing of additive manufactured devices, low force testing of extremity specific devices, and more instrument testing, especially for impact and torsion. Finite element analysis (FEA) is being used to determine worst case size for regulatory testing. OEMs seek high-precision E&L testing for devices designed to reside in the body in order to identify any chemical degradation compounds that could potentially migrate into the patient.
Usability is of increasing interest to the packaging industry. Usability can be considered the cumulative assessment of the physical and cognitive aspects of opening a package and accessing the product. Does the packaging lead the end user to open the package as intended? How are the various aspects tested? Methods for developing these tests, and the associated documentation, are currently being studied.
“OEMs also want assistance with validating their products’ reprocessing instructions for use [IFU],” said Socola. “These include sterilization efficacy testing, cleaning validations, and limits of reuse testing among other tests.”
With ongoing updates to medical device regulations (MDRs), MDMs can also minimize risk by conducting gap assessments between their current data and what is now expected to meet the new requirements. “Transportation and distribution testing are the most common test methods that need to be performed,” said Wendy Mach, consulting manager for Nelson Laboratories. “For example, many companies don’t have actual data on file to prove the robustness of their packaging systems when exposed to the hazards of the shipping environment—working through this type of deficiency is just one example of gaps that need to be addressed.”
As FDA regulations, ISO standards, and MDRs in Europe continue to evolve, MDMs are less confident about the best approach for testing their devices. Increasingly, they turn to their testing partners to select the best testing strategy that complies with regulations and maximizes efficiency.
“Companies are looking for guidance when developing their verification and validation test plans,” said Christopher Scott, vice president of Eurofins Medical Device Testing, a Lancaster, Pa.-based global provider of comprehensive testing services for medical devices. “Given the breadth of testing that is required, it is challenging for OEMs to keep up with the regulatory agencies’ expectations for each area, so they rely on advice from their testing partners.”
The FDA expects OEMs to be knowledgeable about ISO 10993-1 requirements and to provide their testing labs with the programs they feel are appropriate based on their various evaluation plans and risk assessments. “These topics can be very tricky to navigate and OEMs request a lot of input from labs who have seen products like theirs tested before,” said Parker. “Biocompatibility, functional testing, and analytical chemistry aren’t cookie-cutter anymore and labs are being used more to determine the best extraction sample preparation, study designs, or evaluation of abnormal results, especially as the novelty of new device design grows each year.”
New Technological Advances
Perhaps the most exciting trend for testers is the move to in-vitro (non-animal) testing. This has already occurred in the cosmetic and chemical industries and has triggered serious study by MDMs.
“The main successes are with in-vitro irritation and thrombogenicity tests,” said Rollins. “Historically, these endpoints have been evaluated using animal surrogates, but in-vitro methods are replacing these tests. They are currently being evaluated by the FDA and in the next few months we hope to offer these tests as a replacement to the old animal studies.”
Use of 3D tissue models is also increasing. Various 3D tissue culture models (with or without scaffolds) can now replace conventional two-dimensional culture environments, allowing for both characterization and visualization studies using advanced optical imaging systems. “This option allows for the prediction of more complex responses using a more relevant model—human cells instead of animals,” stated Audrey Turley, senior biocompatibility expert for Nelson Laboratories.
Requests for product-specific mechanical testing (such as for strength) may require specialized equipment and tools that are sometimes designed in-house for specific needs. “Many labs can provide standard mechanical testing, but customized, validated methods require more expertise,” said Jennifer Brooks, director of project management for SGS Polymer Solutions. “For example, we can evaluate products while exposing samples to a simulated end-use environment, or fluid exposure at elevated temperature with cyclic loading. We can determine the strength and elongation characteristics of sutures and knots with modified test fixtures. For some projects, we construct test frames and fixtures that confine a sample in a relevant manner during environmental aging.”
Over the past few years, LC-MS instruments (liquid chromatography/mass spectrometry) based on time-of-flight or orbitrap technology have become increasingly prevalent. This equipment detects chemical compounds, such as residual monomers, oligomers, polymer additives, and polymer degradation products, which could migrate out of plastic or rubber materials that are implanted in the body or come into contact with bodily fluids. Examples would be bio-absorbable polymer implants such as plates, pins, screws, and anchors used for orthopedic surgical procedures, or dialysis tubing and membranes.
“These instruments generate mass spectral data with high spectral resolution and high mass accuracy, which is effective for screening analyses looking for unknown extractable and leachable compounds,” said Todd. “These instruments continue to improve in terms of performance, cost, and ease of use.”
The Internet of Things (IoT) is easing its way into the medical device industry, including the testing segment. Testing is becoming increasingly automated (a key IoT technology), which speeds up throughput and reduces testing time significantly. Sensing technologies expand the variety of potential test and analysis applications that physicians and researchers can use to make better-informed decisions remotely, in real time.
“For example, a patient suffering from a non-healing diabetic ulcer may be prescribed a corrective orthotic to help alleviate pressure on the ulcer site,” said Lowe. “This diagnosis is usually a guess-and-check procedure—the patient wears the orthotic for a set period of time, and adjustments are made when necessary. However, with an insole design that incorporates force- and pressure-sensing technology to capture high-pressure points within the patient’s shoe—and that delivers that information to the podiatrist wirelessly to a computer or mobile device—the podiatrist can see quantifiable performance results, in real time.”
Adoption of IoT concepts in the chemical testing laboratory environment, however, is fairly limited, mostly for data integrity and security concerns.
“For several years, manufacturers have been building laboratory instruments with ethernet cards, and in some cases, web browser interfaces, but accessibility of instruments on the Internet is undesirable from a data integrity perspective,” stressed Todd. “Laboratories performing testing in a good manufacturing practice environment are increasingly required to secure their electronic data against unauthorized alteration or deletion.”
Additive manufacturing (AM) and 3D printing are being used in limited situations in the orthopedic market. Although AM can be used to make implants that are customized to a patient’s own body, it is most commonly used to make prototypes. Eager to embrace this technology, some OEMs believe the performance of an AM-manufactured part or product will be the same as a traditionally made part or product.
“This couldn’t be further from the truth,” observed Dawn Lissy, owner of Empirical Testing, a Colorado Springs, Colo.-based provider of mechanical testing for medical devices.
For example, she noted, the combination of variables (methods, cleaning, powder, powder recycling, placement in the machine, etc.) will greatly impact mechanical performance.
“The medical device industry went through a period thinking that polymers act the same as titanium or stainless steel and product development engineers were designing and using historic manufacturing models to apply to polymers,” she continued. “Now the industry has a better understanding of the impact of things like sterilization and cleaning processes on the performance of polymers. We need to apply the same philosophy to additive manufacturing and understand that there are nuances and just because a device behaves the same statically, that does not mean that it will perform the same in dynamic or fatigue scenarios.”
Regulatory Impacts
Various regulatory bodies are continuously changing standards and guidance documents regarding the performance of processing validations. The American Society for Testing and Materials (ASTM) is also creating specifications that target performance criteria for certain products, such as large joints and spinal devices.
“It seems not a week goes by without a new policy or procedure being implemented by the FDA, which is followed by a press release,” said Socola. “I have not seen this much activity in the agency for some time now.”
MDMs continue to face increased scrutiny on data integrity, especially as it applies to test results. Instrumentation software currently provided by manufacturers, or installed on legacy instrumentation and equipment, may not be directly compliant with FDA data integrity requirements. The challenge of ensuring computer systems used for data acquisition are compliant with 21 CFR Part 11 is another factor that compels MDMs to simply outsource testing work.
The FDA focuses on data integrity when it inspects testing labs. Laboratories must be able to show they are generating, storing, and managing electronic data in such a way that it can be demonstrated the data is attributable, legible, contemporaneous/complete, original, and accurate (ALCOA). “This may require testing labs to invest significant time and money in upgrading instrument software, establishing policies and procedural controls, and performing software validation,” said Todd.
The FDA’s increased focus on data integrity—especially process controls intended to minimize the ability of unscrupulous labs to falsify or compromise data sets—does, however, create an additional burden on generating test results. “For example, the FDA may require additional backup technology or additional logging of runs, in response to significant issues the agency has found with some labs and producers,” said Alan Sentman, spectroscopy and applied chemistry laboratory manager for SGS Polymer Solutions.
Moving Forward
The goal for new testing and analysis innovations is the capture of actionable data in a way that does not impede or corrupt a true-to-life testing environment. FEA will be used more to minimize the amount of mechanical testing needed by evaluating what size/geometry combination represents worst case for families of products. Testing and analysis tools will continue to get smaller and more efficient to address demands for usability and convenience.
Testing laboratories design proprietary tests when needed for complex or challenging devices. For example, SGS Polymer Solutions is constantly developing new chromatography test methods to meet unique customer requests. Polymeric materials present unique challenges for chromatographic analysis. “We are currently developing methods for chromatographic analysis of polymers in pharmaceutical formulations, where one or more polymers play a key role as active pharmaceutical ingredient or excipient,” said Todd. “For example, we successfully developed an HPLC [high-performance liquid chromatography] method for assay of three polymer active ingredients, where two other labs before us had failed.”
Labs try to leverage existing methodology whenever they can. For some projects, however, there is nothing available in the literature that will work; in these cases, extensive screening of different chromatographic separation columns and mobile phase solvent compositions are required.
Sometimes the final testing method can be surprisingly simple. For example, an OEM wanted Nelson Labs to evaluate and assess the impact of the addition of printed markings on a patient-contacting surface for its medical device, and the cost of testing was a significant barrier. After exploring the options to assess safety (ranging from animal testing to an aggressive chemistry program), Nelson realized it could assess the safety of the device with printing simply by demonstrating that the ink remains on the device for a certain amount of time. “This way, by using the total amount of ink on the device, we could prove that the amount of systemic exposure from the new substance was below the threshold of toxicological concern,” said Matthew Jorgensen, senior E&L expert for Nelson Laboratories. “What was at first a very time-consuming and expensive testing program was reduced to an almost trivial experiment that involved soaking the device over time, with before and after photos, and a written evaluation.”
Ultimately, it is safest for MDMs to remember that, if they change something about their manufacturing process—whether it is adding a new vendor, or a new machine or cleaning process with an existing vendor—there is the potential for negative impact on the mechanical performance of the medical device, no matter how slight the change might be. This change/impact must be evaluated from both a regulatory and legal perspective.
“Testing evaluation shouldn’t be burdensome,” said Lissy. “The gold standard is two dynamic run-outs with the previously determined run-out load. This simple test can turn up issues that are easier to deal with sooner in the process, rather than later when lots of product is out in the field. We have clients that sold technologies but could not replicate performance because too many ‘small’ design, manufacturer, or process changes had been made and never evaluated. This is a hard road for a root cause analysis—a significant amount of time, parts, and money will be required to unravel the issue, find the cause for change, and fix it.”
Mark Crawford is a full-time freelance business and marketing/communications writer based in Madison, Wis. His clients range from startups to global manufacturing leaders. He also writes a variety of feature articles for regional and national publications and is the author of five books.
There is more to examine in an orthopedic product than ever before. Regulators expect higher-resolution testing of polymeric materials for low molecular weight impurities and additives such as residual monomers and solvents, antioxidants, and light stabilizers. More detailed material compatibility (limits of reuse) and device cleaning studies are often required for 510(k) submissions. And it’s not just devices that need testing—packaging is also under considerable scrutiny, including its usability and impact to the environment.
As a result, testing and analysis in the medical device industry is on the verge of dramatic change. Many standards are being rewritten, with regulatory bodies more willing to accept new analytical techniques. Regulators are also developing a deeper understanding of the complexities of chemistry testing for toxicological risk assessment and biocompatibility, which will likely lead to more scrutiny of analytical methods. Testing laboratories, therefore, must be at the top of their game.
“If you did testing just a year ago, the current requirements might surprise you,” said Thor Rollins, director of extractables and leachables (E&L) consulting for Nelson Laboratories, a Salt Lake City, Utah-based medical device testing laboratory.
The U.S. Food and Drug Administration (FDA) continues to push medical device manufacturers (MDMs) and their supply chain partners to build risk evaluation into every step of the medical device design process. This includes selecting safe raw materials, working with reputable vendors, and using the most suitable manufacturing and sterilization processes.
“Such risk-based planning not only helps develop safer devices, but also identify any required testing,” said Chris Parker, associate department head for Toxikon, a Bedford, Mass.-based provider of in vivo, in-vitro, and analytical testing services for the medical device industry. “Analytical chemistry evaluation, such as E&L, is becoming more of a requirement as it provides data for toxicological evaluation. Biocompatibility and functional evaluation testing is also becoming more important globally, with international initiatives such as the Medical Device Directive in Europe.”
Because of these influences, the medical device validation industry is now running at its highest level in the past decade. “Deregulation, corporate and individual tax cuts by the Trump administration, and the restructuring of the FDA have all played a vital role in this recovery,” said Gary J. Socola, president of Rochester, N.Y.-based HIGHPOWER Validation Testing and Lab Services, a provider of reusable medical device cleaning, packaging, and sterilization validation services. “It’s an exciting time for OEM device manufacturers, their suppliers, and service providers.”
Testing and Analysis Trends
Today, medical device testing is all about risk assessment. Medical devices are becoming more complex and are often made from new materials with unique engineered properties. Device designers, however, also use traditional materials and processing when they can, or combine these materials and methods with more advanced technologies.
“Because of these extremes, the traditional testing that was established decades ago just doesn’t make the cut anymore,” said Rollins. “This is why we now rely on risk assessment as the first step to safety, then develop a testing plan that is unique to the inherent risks of that device. The benefit of this approach is increased safety, often accompanied by a decrease in testing.”
With testing equipment becoming more sensitive, risk assessment can be taken even further. For example, because they can now be measured with precision, there is more emphasis on identifying low-level impurities or other compounds that could impact performance or safety. Liquid chromatography-mass spectrometry (LC-MS) plays an important role in the analysis of organic chemical components of medical devices and other products, including low levels of impurities in raw materials, degradation products, contaminants, or chemical elements that may be present in medical devices and other products.
E&L testing—looking for impurities and additives that could migrate out of a medical device into surrounding tissue or bodily fluids—is becoming increasingly important as part of a comprehensive safety evaluation mandated by the FDA and other regulatory bodies. “Manufacturers of bio-absorbable medical implants are expected now to provide data to the FDA characterizing the by-products generated as a result of breakdown of the polymer in the body,” said Jason Todd, chromatography laboratory manager for SGS Polymer Solutions, a Christiansburg, Va.-based provider of chemical analysis and physical testing of medical devices, pharmaceutical products, and other industrial products.
“These methods can also be used to determine the absence or presence of intentional taggants to deter the use of counterfeit polymers and products,” added James Rancourt, technical director for SGS Polymer Solutions.
As more MDMs utilize electronics and embed sensing technologies into their medical devices, especially orthopedic products, there is greater need to test these functions. For example, force and pressure contact and distribution are important variables in nearly any orthopedic treatment segment. “Whether the purpose is to quantifiably assess an individual’s foot function or gait, or understand how contact surfaces of articulating bones and replacement limbs are functioning or loading, the ability to map pressure distribution presents endless opportunities to enhance orthopedic testing and analysis,” stated Mark Lowe, vice president of sensors for Tekscan, a Boston, Mass.-based manufacturer of ultra-thin tactile force and pressure sensors to optimize medical product design. “Not only are these sensors thin, flexible, and customizable for capturing force in specific spaces, they can operate on simple electronics, which improves power efficiency.”
Implementation of FDA rules for unique device identifiers (UDI) on medical devices has resulted in a surge of testing for UDIs. When the UDI system is fully implemented, labels on most devices will include a unique device identifier in human and machine-readable form. During the design control process, many OEMs are testing their reusable devices not only in their FDA-cleared sterilization process, but also their disinfection process. “This makes sense, as this is how the device is used in an actual clinical setting,” said Socola. “We have seen UDIs that were fine when exposed to a sterilization process but became unreadable when the disinfection process was added prior to sterilization. With the various alkaline and other detergents now available in healthcare, disinfection steps should not be over looked when OEMs are performing durability testing on devices with UDI laser etching or imprints.”
What OEMs Want
Risk mitigation is a top priority for OEMs. They want more thorough testing of additive manufactured devices, low force testing of extremity specific devices, and more instrument testing, especially for impact and torsion. Finite element analysis (FEA) is being used to determine worst case size for regulatory testing. OEMs seek high-precision E&L testing for devices designed to reside in the body in order to identify any chemical degradation compounds that could potentially migrate into the patient.
Usability is of increasing interest to the packaging industry. Usability can be considered the cumulative assessment of the physical and cognitive aspects of opening a package and accessing the product. Does the packaging lead the end user to open the package as intended? How are the various aspects tested? Methods for developing these tests, and the associated documentation, are currently being studied.
“OEMs also want assistance with validating their products’ reprocessing instructions for use [IFU],” said Socola. “These include sterilization efficacy testing, cleaning validations, and limits of reuse testing among other tests.”
With ongoing updates to medical device regulations (MDRs), MDMs can also minimize risk by conducting gap assessments between their current data and what is now expected to meet the new requirements. “Transportation and distribution testing are the most common test methods that need to be performed,” said Wendy Mach, consulting manager for Nelson Laboratories. “For example, many companies don’t have actual data on file to prove the robustness of their packaging systems when exposed to the hazards of the shipping environment—working through this type of deficiency is just one example of gaps that need to be addressed.”
As FDA regulations, ISO standards, and MDRs in Europe continue to evolve, MDMs are less confident about the best approach for testing their devices. Increasingly, they turn to their testing partners to select the best testing strategy that complies with regulations and maximizes efficiency.
“Companies are looking for guidance when developing their verification and validation test plans,” said Christopher Scott, vice president of Eurofins Medical Device Testing, a Lancaster, Pa.-based global provider of comprehensive testing services for medical devices. “Given the breadth of testing that is required, it is challenging for OEMs to keep up with the regulatory agencies’ expectations for each area, so they rely on advice from their testing partners.”
The FDA expects OEMs to be knowledgeable about ISO 10993-1 requirements and to provide their testing labs with the programs they feel are appropriate based on their various evaluation plans and risk assessments. “These topics can be very tricky to navigate and OEMs request a lot of input from labs who have seen products like theirs tested before,” said Parker. “Biocompatibility, functional testing, and analytical chemistry aren’t cookie-cutter anymore and labs are being used more to determine the best extraction sample preparation, study designs, or evaluation of abnormal results, especially as the novelty of new device design grows each year.”
New Technological Advances
Perhaps the most exciting trend for testers is the move to in-vitro (non-animal) testing. This has already occurred in the cosmetic and chemical industries and has triggered serious study by MDMs.
“The main successes are with in-vitro irritation and thrombogenicity tests,” said Rollins. “Historically, these endpoints have been evaluated using animal surrogates, but in-vitro methods are replacing these tests. They are currently being evaluated by the FDA and in the next few months we hope to offer these tests as a replacement to the old animal studies.”
Use of 3D tissue models is also increasing. Various 3D tissue culture models (with or without scaffolds) can now replace conventional two-dimensional culture environments, allowing for both characterization and visualization studies using advanced optical imaging systems. “This option allows for the prediction of more complex responses using a more relevant model—human cells instead of animals,” stated Audrey Turley, senior biocompatibility expert for Nelson Laboratories.
Requests for product-specific mechanical testing (such as for strength) may require specialized equipment and tools that are sometimes designed in-house for specific needs. “Many labs can provide standard mechanical testing, but customized, validated methods require more expertise,” said Jennifer Brooks, director of project management for SGS Polymer Solutions. “For example, we can evaluate products while exposing samples to a simulated end-use environment, or fluid exposure at elevated temperature with cyclic loading. We can determine the strength and elongation characteristics of sutures and knots with modified test fixtures. For some projects, we construct test frames and fixtures that confine a sample in a relevant manner during environmental aging.”
Over the past few years, LC-MS instruments (liquid chromatography/mass spectrometry) based on time-of-flight or orbitrap technology have become increasingly prevalent. This equipment detects chemical compounds, such as residual monomers, oligomers, polymer additives, and polymer degradation products, which could migrate out of plastic or rubber materials that are implanted in the body or come into contact with bodily fluids. Examples would be bio-absorbable polymer implants such as plates, pins, screws, and anchors used for orthopedic surgical procedures, or dialysis tubing and membranes.
“These instruments generate mass spectral data with high spectral resolution and high mass accuracy, which is effective for screening analyses looking for unknown extractable and leachable compounds,” said Todd. “These instruments continue to improve in terms of performance, cost, and ease of use.”
The Internet of Things (IoT) is easing its way into the medical device industry, including the testing segment. Testing is becoming increasingly automated (a key IoT technology), which speeds up throughput and reduces testing time significantly. Sensing technologies expand the variety of potential test and analysis applications that physicians and researchers can use to make better-informed decisions remotely, in real time.
“For example, a patient suffering from a non-healing diabetic ulcer may be prescribed a corrective orthotic to help alleviate pressure on the ulcer site,” said Lowe. “This diagnosis is usually a guess-and-check procedure—the patient wears the orthotic for a set period of time, and adjustments are made when necessary. However, with an insole design that incorporates force- and pressure-sensing technology to capture high-pressure points within the patient’s shoe—and that delivers that information to the podiatrist wirelessly to a computer or mobile device—the podiatrist can see quantifiable performance results, in real time.”
Adoption of IoT concepts in the chemical testing laboratory environment, however, is fairly limited, mostly for data integrity and security concerns.
“For several years, manufacturers have been building laboratory instruments with ethernet cards, and in some cases, web browser interfaces, but accessibility of instruments on the Internet is undesirable from a data integrity perspective,” stressed Todd. “Laboratories performing testing in a good manufacturing practice environment are increasingly required to secure their electronic data against unauthorized alteration or deletion.”
Additive manufacturing (AM) and 3D printing are being used in limited situations in the orthopedic market. Although AM can be used to make implants that are customized to a patient’s own body, it is most commonly used to make prototypes. Eager to embrace this technology, some OEMs believe the performance of an AM-manufactured part or product will be the same as a traditionally made part or product.
“This couldn’t be further from the truth,” observed Dawn Lissy, owner of Empirical Testing, a Colorado Springs, Colo.-based provider of mechanical testing for medical devices.
For example, she noted, the combination of variables (methods, cleaning, powder, powder recycling, placement in the machine, etc.) will greatly impact mechanical performance.
“The medical device industry went through a period thinking that polymers act the same as titanium or stainless steel and product development engineers were designing and using historic manufacturing models to apply to polymers,” she continued. “Now the industry has a better understanding of the impact of things like sterilization and cleaning processes on the performance of polymers. We need to apply the same philosophy to additive manufacturing and understand that there are nuances and just because a device behaves the same statically, that does not mean that it will perform the same in dynamic or fatigue scenarios.”
Regulatory Impacts
Various regulatory bodies are continuously changing standards and guidance documents regarding the performance of processing validations. The American Society for Testing and Materials (ASTM) is also creating specifications that target performance criteria for certain products, such as large joints and spinal devices.
“It seems not a week goes by without a new policy or procedure being implemented by the FDA, which is followed by a press release,” said Socola. “I have not seen this much activity in the agency for some time now.”
MDMs continue to face increased scrutiny on data integrity, especially as it applies to test results. Instrumentation software currently provided by manufacturers, or installed on legacy instrumentation and equipment, may not be directly compliant with FDA data integrity requirements. The challenge of ensuring computer systems used for data acquisition are compliant with 21 CFR Part 11 is another factor that compels MDMs to simply outsource testing work.
The FDA focuses on data integrity when it inspects testing labs. Laboratories must be able to show they are generating, storing, and managing electronic data in such a way that it can be demonstrated the data is attributable, legible, contemporaneous/complete, original, and accurate (ALCOA). “This may require testing labs to invest significant time and money in upgrading instrument software, establishing policies and procedural controls, and performing software validation,” said Todd.
The FDA’s increased focus on data integrity—especially process controls intended to minimize the ability of unscrupulous labs to falsify or compromise data sets—does, however, create an additional burden on generating test results. “For example, the FDA may require additional backup technology or additional logging of runs, in response to significant issues the agency has found with some labs and producers,” said Alan Sentman, spectroscopy and applied chemistry laboratory manager for SGS Polymer Solutions.
Moving Forward
The goal for new testing and analysis innovations is the capture of actionable data in a way that does not impede or corrupt a true-to-life testing environment. FEA will be used more to minimize the amount of mechanical testing needed by evaluating what size/geometry combination represents worst case for families of products. Testing and analysis tools will continue to get smaller and more efficient to address demands for usability and convenience.
Testing laboratories design proprietary tests when needed for complex or challenging devices. For example, SGS Polymer Solutions is constantly developing new chromatography test methods to meet unique customer requests. Polymeric materials present unique challenges for chromatographic analysis. “We are currently developing methods for chromatographic analysis of polymers in pharmaceutical formulations, where one or more polymers play a key role as active pharmaceutical ingredient or excipient,” said Todd. “For example, we successfully developed an HPLC [high-performance liquid chromatography] method for assay of three polymer active ingredients, where two other labs before us had failed.”
Labs try to leverage existing methodology whenever they can. For some projects, however, there is nothing available in the literature that will work; in these cases, extensive screening of different chromatographic separation columns and mobile phase solvent compositions are required.
Sometimes the final testing method can be surprisingly simple. For example, an OEM wanted Nelson Labs to evaluate and assess the impact of the addition of printed markings on a patient-contacting surface for its medical device, and the cost of testing was a significant barrier. After exploring the options to assess safety (ranging from animal testing to an aggressive chemistry program), Nelson realized it could assess the safety of the device with printing simply by demonstrating that the ink remains on the device for a certain amount of time. “This way, by using the total amount of ink on the device, we could prove that the amount of systemic exposure from the new substance was below the threshold of toxicological concern,” said Matthew Jorgensen, senior E&L expert for Nelson Laboratories. “What was at first a very time-consuming and expensive testing program was reduced to an almost trivial experiment that involved soaking the device over time, with before and after photos, and a written evaluation.”
Ultimately, it is safest for MDMs to remember that, if they change something about their manufacturing process—whether it is adding a new vendor, or a new machine or cleaning process with an existing vendor—there is the potential for negative impact on the mechanical performance of the medical device, no matter how slight the change might be. This change/impact must be evaluated from both a regulatory and legal perspective.
“Testing evaluation shouldn’t be burdensome,” said Lissy. “The gold standard is two dynamic run-outs with the previously determined run-out load. This simple test can turn up issues that are easier to deal with sooner in the process, rather than later when lots of product is out in the field. We have clients that sold technologies but could not replicate performance because too many ‘small’ design, manufacturer, or process changes had been made and never evaluated. This is a hard road for a root cause analysis—a significant amount of time, parts, and money will be required to unravel the issue, find the cause for change, and fix it.”
Mark Crawford is a full-time freelance business and marketing/communications writer based in Madison, Wis. His clients range from startups to global manufacturing leaders. He also writes a variety of feature articles for regional and national publications and is the author of five books.