Mark Crawford, Contributing Writer03.11.15
Medical device manufacturers are asking a lot more of their testing partners these days. Regulations are more stringent, requiring more tests. Devices are becoming more complex, with multiple components and advanced materials, which require different kinds of tests. Even the definition of “clean” is in limbo because analytical precision is so high that chemicals that once were undetectable can now be detected, raising the question of whether they pose health risks. Further, there are no well-defined testing protocols required by regulatory bodies—it is up to device firms and their testing partners to devise the right tests and provide the supporting data that shows the device meets or exceeds regulatory expectations.
“Many clients still expect to provide stacks of data to regulators for their review and interpretation,” said Lisa Olson, vice president of marketing and testing services at the St. Paul, Minn., facilities of WuXi AppTec, a China-based global contract research provider to the medical device industry. “In reality, regulatory reviewers have huge workloads and don’t have the time to do this. The manufacturer is responsible for providing a thorough and cogent argument that demonstrates the safety and efficacy of the product, backed up by comprehensive data. The reviewers have the responsibility to determine if the burden of proof required in the regulation was met.”
This all means that testers must be on top of their game when it comes to knowing the regulations, being innovative in designing testing methods, and planning proactively for what’s on the horizon with regulatory trends and medical device design.
With these complications and challenges, medical device manufacturers are evaluating every aspect of the design and manufacturing operation in order to streamline production and control costs. This includes trying risk-based approaches to product and process validation. By validating methods earlier in the process, method feasibility or small-scale initial validation studies on methods can be used to ensure that data on the finished product, once fully developed, will still be comparable and acceptable for submission.
“More companies are looking beyond the device and validating the process,” said John Bolinder, vice president of integrated marketing and communications for Nelson Laboratories Inc., a Salt Lake City, Utah-based provider of full life-cycle microbiology testing services for the medical device industry. “Take 3-D-printed devices, for example. Validation of the process is taking over validation of the device to ensure safety and efficacy using risk-based approaches. Process and material controls are essential for successful validation of 3-D-printed devices. This results in new approaches to biocompatibility, sterility assurance, and other classic test models, which then typically require additional assessments and justifications.”
To speed up testing and approval, OEMs try to stay with proven materials and technologies that already have been validated and are supported by a large body of testing and performance data accepted by regulatory agencies. For many mature medical device technologies, ASTM and ISO standards provide the essential components of the test methods for comparing to previous designs or predicate devices.
“However, as new technologies emerge such as ankle replacement systems, reverse shoulder systems, and expandable intervertebral body fusion devices, new testing methodologies are developed and validated to adequately characterize the device,” said Dawn Lissy, president of Empirical Testing Corp., a Colorado Springs, Colo.-based provider of mechanical testing for medical devices. “Historically, for example, extremity and trauma products have been considered mature—but with the recent trend toward new materials or geometries, some alterations to test standards may be required.”
Strengthening Biocompatibility
Regulatory agencies increasingly are concerned that standard extraction methodologies for biological tests are not effective enough to fully assess risk. An increasing trend in biological evaluations is the need to tie all the data together into a cohesive package. Agencies are requesting more chemical tests than ever before, which “are a lot more sophisticated than three years ago,” said Olson. “Therefore the need for biological evaluations or risk assessments has become much more critical to make sense of the chemistry.”
Using chemical characterization data in toxicological assessments is rapidly becoming an accepted approach in the medical device industry.
“We have seen an increase in chemical characterization assessment data requests from the FDA (U.S. Food and Drug Administration), where the agency wants more additional biocompatibility testing or chemical characterization and toxicological assessments from clients during their submission process,” said Bolinder.
This is largely due to harmonized ISO 10993 and new FDA guidance that has changed the classical approach to biocompatibility assessments. Companies no longer can just follow the matrix as published in ISO 10993 in a “check box” manner. The new FDA guidance issued April 2013 calls for risk and safety assessments, chemical or material characterization, and biocompatibility testing of the device, with the expectation that the recommended testing (or justification for testing not performed) will demonstrate the manufacturer assessed all safety risks.
“The guidance specifically discusses the need for OEMs to look at the biocompatibility matrix as a guideline only, then perform testing as recommended in the matrix or justify why it was not performed, even on known materials,” said Bolinder. “This results in new demand for product risk assessments, toxicological review of analytical data, and solid, written justifications for device-specific test plans and strategies before performing biocompatibility tests.”
This, of course, is a lot more work. To deal with it effectively, OEMs and their partners are testing early in the development process to help select and source materials for their products using materials characterization. This can save lots of time later in the process and avoid failures.
“Our technical experts work with research and development teams to not only develop testing plans, but discuss the inherent details of certain materials and processing of those materials as they relate to medical device safety,” said Olson.
Risk assessments aren’t just for justifying questionable materials anymore—they have evolved to the point where they add real value to the design and use of the project. For example, toxicologists use risk assessments to demonstrate safety of products that may have concerns based on chemistry testing. When combined with smart design of biocompatibility testing programs, however, they also can improve quality and performance.
“Because risk assessments can be used at so many points, they are helping to drive product development at earlier stages than ever before,” explained Olson. “For example, evaluating colorants early in product development can be the difference in the scope of later submissions testing and regulatory scrutiny.”
Pushing the Limits of Technology
The FDA is becoming more vigilant regarding sterile products and manufacturing conditions. A more stringent assessment of cleanliness may impact biocompatibility and sterility assurance. The limits of detection for many chromatographic test systems have become so low that remnant vapors from a processing aid can be detected. As a result, more chemicals are being identified as part of materials characterization.
This is important, Olson pointed out, because having “unknowns” can be problematic from a risk perspective. “If you can’t positively identify a chemical, then the worst case must be assumed,” she said. “This means that regulators must consider unknowns to be carcinogenic or genotoxic, which can result in failed submissions or requests for additional testing or failed submissions.”
“Many companies are struggling with what tests and how much testing will be required to show that their processes are clean, and that their products are clean on a lot-to-lot basis,” said Jarret Wright, thermal, physical and microscopy lab manager at Polymer Solutions Inc., a Christiansburg, Va.-based materials analysis and testing laboratory. “Simply targeting all the necessary analytes can seem like a daunting task when you consider all the ingredients in every material used in a manufacturing process, not to mention any of their derivatives that may have been formed from heat or chemical sterilization steps. Complete validation of process cleanliness often involves a multi-tiered approach with different specific tests on multiple test platforms.”
This can drive up costs. An example is testing for residues, which might require both aqueous and non-polar solvent extractions for high-performance liquid chromatography, as well as testing for volatiles by gas chromatography. Each step in the process adds more cost, which potentially could make or break the profit margin on a new product, especially for startup companies.
Many organizations are conducting more feasibility testing to further understand their package system prior to the execution of final package validation. Failures sometimes result because the selected packaging system was not the best choice for the product. For example, pouch systems are not suitable for every product. Heavy products or products with sharp or irregular geometries often are best protected with a rigid tray system.
“The overall misconception is that using an existing pouch with new products will get them to market faster,” said Scott Levy, senior packaging engineer for DDL, an Eden Prairie, Minn.-based medical device testing laboratory. “In many cases, this decision results in catastrophic results that delay the launch of product. Understanding your design inputs is critical to picking the correct sterile barrier system and keeping the sterility maintenance intact.”
Advances in film extrusion technology are now challenging the limits of microscopy techniques. Today’s complex films for use in implant devices and food and pharmaceutical packaging sometimes consist of a dozen layers of varying polymers, adhesives, and metal foils, which when combined total less than a millimeter in thickness. Imaging and analyzing these layers are beyond the limits of a common optical microscope, which is constrained by light transmittance and depth of field issues. The composition of the various layers can be so similar that visualizing them can be difficult, even with the exponential magnification power of a scanning electron microscope.
“To meet these challenges, innovative techniques with refracted light, hot stage, or oil immersion, or multi-layered focusing systems such as Hirox or Keyence are sometimes required,” said Wright. “Hot stage microscopy allows the sample to be heated at a controlled rate through the temperature range where the various layers melt. Changes in light transmittance can be seen in the individual layers as they reach the onsets and peaks of their melt transitions.”
Many microscopy techniques require that the specimens be in a particular form for testing. If one layer is significantly stronger, or an adhesive layer is significantly weaker, sections of the sample will “pull out” instead of cutting cleanly. “A multi-layered focusing system takes several images in various focusing planes,” added Wright. “Sometimes this allows the recesses left from pulled-out sections to be in focus with the rest of the sample.”
Another boundary that is being challenged is accelerated aging and elevating temperature of products, which are techniques that attempt to shorten the process, getting products to market faster.
“Understanding the use of accelerated aging prior to generating a timeline is critical to the overall success of the validation as well as keeping management happy,” said Levy.
It takes a significant amount of time to complete a package validation, including stability, performance, strength, and integrity testing. Most of this validation time is spent in accelerated aging.
“Some companies think they can speed up this process by shortening the time duration within the aging cycle by increasing the temperature,” Levy told Medical Product Outsourcing. “This, however, can cause catastrophic results to the product and or packaging system.”
Regulatory Trends
Regulations (and the interpretation of regulations) continue to evolve and expand. A product that was readily approved in the past, even as recently as six months ago, may have issues today based on the requirements and how they are interpreted by different regulatory bodies.
Most new test method requests are the result of regulatory or notified body audits occurring at medical device manufacturing facilities, especially for orthopedic and implant device cleanliness and particulates on cardiovascular devices. The primary concern is that contaminants may be on the device that is not intended to be part of the implanted device, which could cause adverse patient impact. This is especially true for cardiovascular devices, which have more complex geometries and are made from multiple materials, including advanced coatings. Contamination sources include particulates from machining processes, soap, oil and lubricant residuals from these same processes and facility, or environmental contaminants including water sources.
“All manufacturers of implants should assess and validate their cleaning steps to ensure the device does not contain soluble and nonsoluble residues, particulates or microbial by-products of the manufacturing process as outlined in ASTM F2847 as well as draft ISO 19227 guidance from ISO/TC 150 which is expected to publish soon,” Nelson Labs’ Bolinder noted. “Although end-use device testing may indicate the device is sterile, it is important to remember that biocompatible, sterile and clean are different.”
Nelson Labs also has seen an increase in audit observations related to water quality in the manufacturing facility. Some manufacturers have failed to define their utility and critical water, including validation and routine monitoring of these systems. Staff overseeing water systems should be trained on water system quality, action, and alert limits, as well as general concepts in water system design, to ensure design qualification and user requirements meet manufacturer-specific acceptance criteria.
“Where specific guidance is not given for medical device manufacturers there is good guidance coming in AAMI TIR 34 for healthcare facilities that can be modeled for the manufacturing environment in conjunction with USP and other standards for water quality,” said Bolinder.
Clinical reprocessing of endoscopes also is getting renewed attention. In recent weeks “superbug” infections have resulted in the deaths of patients who contracted infectious organisms from endoscopic procedures (see Washington Roundup on page 18). Although other factors also could be involved such as improper reprocessing at the healthcare facility, difficult and complex device designs, or inadequate validated disinfection or cleaning procedures, it is evident from the FDA safety communication issued in February that these complex devices may require additional care and validation.
Partnerships Matter
Meeting quality, cost and delivery objectives with a proactive team spirit is the mark of a successful partnership between an OEM or contract manufacturer and a testing facility. Testing is one of the most critical parts that make it all happen.
“There is significant investment in performing the mechanical testing correctly,” said Lissy. “The outcome is the foundation for the device—for the current design and all future design and/or manufacturing changes.”
OEMs and testing firms strive to build long-term partnerships that require shared vision and transparency of knowledge and details, and exchange of ideas during the design phase. This way the tester can share expertise that significantly could improve material selection and medical device design, or work with the OEM to develop new testing methods when needed, especially for emerging technologies.
Recently, Empirical Testing changed the testing paradigm of a spinal wear tester and used it to characterize the wear of a new material against animal cartilage.
“This was an innovative approach to characterizing the device and answered a specific regulatory question because previously used materials in the test configuration were pre-failing the subject device in an unrealistic manner,” said Lissy. “ETC partnered with the client to determine realistic failure modes and the best components for the mechanical testing to have relevant data.”
A successful testing strategy depends on having a solid regulatory plan, a test plan that accurately characterizes the overall performance of the device (whether by testing to an ASTM or ISO or a custom protocol), performing a comprehensive failure modes and effects analysis and creating custom test protocols that address any issues that result from the analysis, as well as using solid science to have reproducible, accurate, and traceable testing results.
At times this also means telling customers what they don’t want to hear.
For example, according to Lissy, customers often want to know if testing will go faster if they use multiple frames.
“The short answer is yes,” she said. “The real answer is it depends on the strategy. If the plan is to validate a new manufacturing vendor or process and we understand the existing properties of the device, then it is reasonable to utilize multiple frames.
However, if no feasibility or previous testing has been performed, using multiple test frames is like putting on a blindfold and shooting darts at the dart board. What if all the specimens at the different loads reach the endurance load as cited by the protocol? Or what if all the specimens fail at the different load levels? If there is no plan for the testing, typically more time, specimens, and dollars are spent on the testing exercise than the client expected.”
Design medical devices with the end in mind, advised Bolinder—that includes sterilization and reprocessing, not just clinical functionality. The testing firm should be allowed (and encouraged) to impart its testing wisdom during the design stage as a trusted partner. For example, matted surfaces, adhesives, or polymers can be incompatible with common healthcare disinfectants or sterilization processes—something medical device makers might not know. Long lumens may make it difficult to sterilize or impossible to clean the device in the healthcare setting, which increases patient risk. Healthcare workers then may need to reprocess the device more than once between uses to fully clean or disinfect after visual inspections.
“Unfortunately,” said Bolinder, “this is sometimes only considered at the end of the design process, or just prior to clinical or regulatory submissions, resulting in test and product delays due to unexpected failures in test validation. Testing and validation timelines can be improved when the sterilization and cleaning experts, either at the manufacturer’s facility or in collaboration with the laboratory, are consulted early in the design phase.”
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. Contact him at mark.crawford@charter.net.
“Many clients still expect to provide stacks of data to regulators for their review and interpretation,” said Lisa Olson, vice president of marketing and testing services at the St. Paul, Minn., facilities of WuXi AppTec, a China-based global contract research provider to the medical device industry. “In reality, regulatory reviewers have huge workloads and don’t have the time to do this. The manufacturer is responsible for providing a thorough and cogent argument that demonstrates the safety and efficacy of the product, backed up by comprehensive data. The reviewers have the responsibility to determine if the burden of proof required in the regulation was met.”
This all means that testers must be on top of their game when it comes to knowing the regulations, being innovative in designing testing methods, and planning proactively for what’s on the horizon with regulatory trends and medical device design.
With these complications and challenges, medical device manufacturers are evaluating every aspect of the design and manufacturing operation in order to streamline production and control costs. This includes trying risk-based approaches to product and process validation. By validating methods earlier in the process, method feasibility or small-scale initial validation studies on methods can be used to ensure that data on the finished product, once fully developed, will still be comparable and acceptable for submission.
“More companies are looking beyond the device and validating the process,” said John Bolinder, vice president of integrated marketing and communications for Nelson Laboratories Inc., a Salt Lake City, Utah-based provider of full life-cycle microbiology testing services for the medical device industry. “Take 3-D-printed devices, for example. Validation of the process is taking over validation of the device to ensure safety and efficacy using risk-based approaches. Process and material controls are essential for successful validation of 3-D-printed devices. This results in new approaches to biocompatibility, sterility assurance, and other classic test models, which then typically require additional assessments and justifications.”
To speed up testing and approval, OEMs try to stay with proven materials and technologies that already have been validated and are supported by a large body of testing and performance data accepted by regulatory agencies. For many mature medical device technologies, ASTM and ISO standards provide the essential components of the test methods for comparing to previous designs or predicate devices.
“However, as new technologies emerge such as ankle replacement systems, reverse shoulder systems, and expandable intervertebral body fusion devices, new testing methodologies are developed and validated to adequately characterize the device,” said Dawn Lissy, president of Empirical Testing Corp., a Colorado Springs, Colo.-based provider of mechanical testing for medical devices. “Historically, for example, extremity and trauma products have been considered mature—but with the recent trend toward new materials or geometries, some alterations to test standards may be required.”
Strengthening Biocompatibility
Regulatory agencies increasingly are concerned that standard extraction methodologies for biological tests are not effective enough to fully assess risk. An increasing trend in biological evaluations is the need to tie all the data together into a cohesive package. Agencies are requesting more chemical tests than ever before, which “are a lot more sophisticated than three years ago,” said Olson. “Therefore the need for biological evaluations or risk assessments has become much more critical to make sense of the chemistry.”
Using chemical characterization data in toxicological assessments is rapidly becoming an accepted approach in the medical device industry.
“We have seen an increase in chemical characterization assessment data requests from the FDA (U.S. Food and Drug Administration), where the agency wants more additional biocompatibility testing or chemical characterization and toxicological assessments from clients during their submission process,” said Bolinder.
This is largely due to harmonized ISO 10993 and new FDA guidance that has changed the classical approach to biocompatibility assessments. Companies no longer can just follow the matrix as published in ISO 10993 in a “check box” manner. The new FDA guidance issued April 2013 calls for risk and safety assessments, chemical or material characterization, and biocompatibility testing of the device, with the expectation that the recommended testing (or justification for testing not performed) will demonstrate the manufacturer assessed all safety risks.
“The guidance specifically discusses the need for OEMs to look at the biocompatibility matrix as a guideline only, then perform testing as recommended in the matrix or justify why it was not performed, even on known materials,” said Bolinder. “This results in new demand for product risk assessments, toxicological review of analytical data, and solid, written justifications for device-specific test plans and strategies before performing biocompatibility tests.”
This, of course, is a lot more work. To deal with it effectively, OEMs and their partners are testing early in the development process to help select and source materials for their products using materials characterization. This can save lots of time later in the process and avoid failures.
“Our technical experts work with research and development teams to not only develop testing plans, but discuss the inherent details of certain materials and processing of those materials as they relate to medical device safety,” said Olson.
Risk assessments aren’t just for justifying questionable materials anymore—they have evolved to the point where they add real value to the design and use of the project. For example, toxicologists use risk assessments to demonstrate safety of products that may have concerns based on chemistry testing. When combined with smart design of biocompatibility testing programs, however, they also can improve quality and performance.
“Because risk assessments can be used at so many points, they are helping to drive product development at earlier stages than ever before,” explained Olson. “For example, evaluating colorants early in product development can be the difference in the scope of later submissions testing and regulatory scrutiny.”
Pushing the Limits of Technology
The FDA is becoming more vigilant regarding sterile products and manufacturing conditions. A more stringent assessment of cleanliness may impact biocompatibility and sterility assurance. The limits of detection for many chromatographic test systems have become so low that remnant vapors from a processing aid can be detected. As a result, more chemicals are being identified as part of materials characterization.
This is important, Olson pointed out, because having “unknowns” can be problematic from a risk perspective. “If you can’t positively identify a chemical, then the worst case must be assumed,” she said. “This means that regulators must consider unknowns to be carcinogenic or genotoxic, which can result in failed submissions or requests for additional testing or failed submissions.”
“Many companies are struggling with what tests and how much testing will be required to show that their processes are clean, and that their products are clean on a lot-to-lot basis,” said Jarret Wright, thermal, physical and microscopy lab manager at Polymer Solutions Inc., a Christiansburg, Va.-based materials analysis and testing laboratory. “Simply targeting all the necessary analytes can seem like a daunting task when you consider all the ingredients in every material used in a manufacturing process, not to mention any of their derivatives that may have been formed from heat or chemical sterilization steps. Complete validation of process cleanliness often involves a multi-tiered approach with different specific tests on multiple test platforms.”
This can drive up costs. An example is testing for residues, which might require both aqueous and non-polar solvent extractions for high-performance liquid chromatography, as well as testing for volatiles by gas chromatography. Each step in the process adds more cost, which potentially could make or break the profit margin on a new product, especially for startup companies.
Many organizations are conducting more feasibility testing to further understand their package system prior to the execution of final package validation. Failures sometimes result because the selected packaging system was not the best choice for the product. For example, pouch systems are not suitable for every product. Heavy products or products with sharp or irregular geometries often are best protected with a rigid tray system.
“The overall misconception is that using an existing pouch with new products will get them to market faster,” said Scott Levy, senior packaging engineer for DDL, an Eden Prairie, Minn.-based medical device testing laboratory. “In many cases, this decision results in catastrophic results that delay the launch of product. Understanding your design inputs is critical to picking the correct sterile barrier system and keeping the sterility maintenance intact.”
Advances in film extrusion technology are now challenging the limits of microscopy techniques. Today’s complex films for use in implant devices and food and pharmaceutical packaging sometimes consist of a dozen layers of varying polymers, adhesives, and metal foils, which when combined total less than a millimeter in thickness. Imaging and analyzing these layers are beyond the limits of a common optical microscope, which is constrained by light transmittance and depth of field issues. The composition of the various layers can be so similar that visualizing them can be difficult, even with the exponential magnification power of a scanning electron microscope.
“To meet these challenges, innovative techniques with refracted light, hot stage, or oil immersion, or multi-layered focusing systems such as Hirox or Keyence are sometimes required,” said Wright. “Hot stage microscopy allows the sample to be heated at a controlled rate through the temperature range where the various layers melt. Changes in light transmittance can be seen in the individual layers as they reach the onsets and peaks of their melt transitions.”
Many microscopy techniques require that the specimens be in a particular form for testing. If one layer is significantly stronger, or an adhesive layer is significantly weaker, sections of the sample will “pull out” instead of cutting cleanly. “A multi-layered focusing system takes several images in various focusing planes,” added Wright. “Sometimes this allows the recesses left from pulled-out sections to be in focus with the rest of the sample.”
Another boundary that is being challenged is accelerated aging and elevating temperature of products, which are techniques that attempt to shorten the process, getting products to market faster.
“Understanding the use of accelerated aging prior to generating a timeline is critical to the overall success of the validation as well as keeping management happy,” said Levy.
It takes a significant amount of time to complete a package validation, including stability, performance, strength, and integrity testing. Most of this validation time is spent in accelerated aging.
“Some companies think they can speed up this process by shortening the time duration within the aging cycle by increasing the temperature,” Levy told Medical Product Outsourcing. “This, however, can cause catastrophic results to the product and or packaging system.”
Regulatory Trends
Regulations (and the interpretation of regulations) continue to evolve and expand. A product that was readily approved in the past, even as recently as six months ago, may have issues today based on the requirements and how they are interpreted by different regulatory bodies.
Most new test method requests are the result of regulatory or notified body audits occurring at medical device manufacturing facilities, especially for orthopedic and implant device cleanliness and particulates on cardiovascular devices. The primary concern is that contaminants may be on the device that is not intended to be part of the implanted device, which could cause adverse patient impact. This is especially true for cardiovascular devices, which have more complex geometries and are made from multiple materials, including advanced coatings. Contamination sources include particulates from machining processes, soap, oil and lubricant residuals from these same processes and facility, or environmental contaminants including water sources.
“All manufacturers of implants should assess and validate their cleaning steps to ensure the device does not contain soluble and nonsoluble residues, particulates or microbial by-products of the manufacturing process as outlined in ASTM F2847 as well as draft ISO 19227 guidance from ISO/TC 150 which is expected to publish soon,” Nelson Labs’ Bolinder noted. “Although end-use device testing may indicate the device is sterile, it is important to remember that biocompatible, sterile and clean are different.”
Nelson Labs also has seen an increase in audit observations related to water quality in the manufacturing facility. Some manufacturers have failed to define their utility and critical water, including validation and routine monitoring of these systems. Staff overseeing water systems should be trained on water system quality, action, and alert limits, as well as general concepts in water system design, to ensure design qualification and user requirements meet manufacturer-specific acceptance criteria.
“Where specific guidance is not given for medical device manufacturers there is good guidance coming in AAMI TIR 34 for healthcare facilities that can be modeled for the manufacturing environment in conjunction with USP and other standards for water quality,” said Bolinder.
Clinical reprocessing of endoscopes also is getting renewed attention. In recent weeks “superbug” infections have resulted in the deaths of patients who contracted infectious organisms from endoscopic procedures (see Washington Roundup on page 18). Although other factors also could be involved such as improper reprocessing at the healthcare facility, difficult and complex device designs, or inadequate validated disinfection or cleaning procedures, it is evident from the FDA safety communication issued in February that these complex devices may require additional care and validation.
Partnerships Matter
Meeting quality, cost and delivery objectives with a proactive team spirit is the mark of a successful partnership between an OEM or contract manufacturer and a testing facility. Testing is one of the most critical parts that make it all happen.
“There is significant investment in performing the mechanical testing correctly,” said Lissy. “The outcome is the foundation for the device—for the current design and all future design and/or manufacturing changes.”
OEMs and testing firms strive to build long-term partnerships that require shared vision and transparency of knowledge and details, and exchange of ideas during the design phase. This way the tester can share expertise that significantly could improve material selection and medical device design, or work with the OEM to develop new testing methods when needed, especially for emerging technologies.
Recently, Empirical Testing changed the testing paradigm of a spinal wear tester and used it to characterize the wear of a new material against animal cartilage.
“This was an innovative approach to characterizing the device and answered a specific regulatory question because previously used materials in the test configuration were pre-failing the subject device in an unrealistic manner,” said Lissy. “ETC partnered with the client to determine realistic failure modes and the best components for the mechanical testing to have relevant data.”
A successful testing strategy depends on having a solid regulatory plan, a test plan that accurately characterizes the overall performance of the device (whether by testing to an ASTM or ISO or a custom protocol), performing a comprehensive failure modes and effects analysis and creating custom test protocols that address any issues that result from the analysis, as well as using solid science to have reproducible, accurate, and traceable testing results.
At times this also means telling customers what they don’t want to hear.
For example, according to Lissy, customers often want to know if testing will go faster if they use multiple frames.
“The short answer is yes,” she said. “The real answer is it depends on the strategy. If the plan is to validate a new manufacturing vendor or process and we understand the existing properties of the device, then it is reasonable to utilize multiple frames.
However, if no feasibility or previous testing has been performed, using multiple test frames is like putting on a blindfold and shooting darts at the dart board. What if all the specimens at the different loads reach the endurance load as cited by the protocol? Or what if all the specimens fail at the different load levels? If there is no plan for the testing, typically more time, specimens, and dollars are spent on the testing exercise than the client expected.”
Design medical devices with the end in mind, advised Bolinder—that includes sterilization and reprocessing, not just clinical functionality. The testing firm should be allowed (and encouraged) to impart its testing wisdom during the design stage as a trusted partner. For example, matted surfaces, adhesives, or polymers can be incompatible with common healthcare disinfectants or sterilization processes—something medical device makers might not know. Long lumens may make it difficult to sterilize or impossible to clean the device in the healthcare setting, which increases patient risk. Healthcare workers then may need to reprocess the device more than once between uses to fully clean or disinfect after visual inspections.
“Unfortunately,” said Bolinder, “this is sometimes only considered at the end of the design process, or just prior to clinical or regulatory submissions, resulting in test and product delays due to unexpected failures in test validation. Testing and validation timelines can be improved when the sterilization and cleaning experts, either at the manufacturer’s facility or in collaboration with the laboratory, are consulted early in the design phase.”
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. Contact him at mark.crawford@charter.net.