Mark Crawford, Contributing Writer03.13.14
Contract testing for medical devices encompasses a broad variety of tests and products, ranging from circuit boards to in-vivo biocompatibility studies. For the most part, technologies and protocols have stayed about the same over the last few years—the biggest challenge for contract testers is keeping up with increased demands by OEMs for more services and expertise.
Some such demands are driven by evolving regulations such as a revised version of the European Union’s Restriction of Hazardous Substances directive (RoHS II), which takes effect this summer and impacts medical device testing requirements.
Another regulation is U.S. Pharmacopeial Convention (USP) 661, which will require inductively coupled plasma mass spectrometry (ICP-MS) characterization of plastics. More medical OEMs also are auditing their contract testers to ISO 17025 standards instead of current Good Manufacturing Practice (cGMP) compliance.
“The FDA (U.S. Food and Drug Administration) uses risk to categorize which companies get audited and how frequently,” said Megan Evans, technical quality lead for Polymer Solutions Inc., a Blacksburg, Va.-based testing lab that provides chemical, material and analytical testing for the medical industry. “In response, we are applying more risk-based approaches toward client-specific method validations and changes to equipment, instrumentation and our facility in accordance with ICH Q9, a guidance document published by the International Conference on Harmonization (ICH) on Quality Risk Management.”
A high-risk area currently getting lots of FDA attention is compounding pharmacies and sterile injectables (driven in part by recent deaths related to products contaminated with fungal meningitis).
“This industry as a whole is adjusting to increased validation and testing to assure their sterile injectable drugs are safe for patient use,” said Daniel Prince, president of Gibraltar Laboratories Inc., a Fairfield, N.J.-based provider of chemical and biological testing and steam sterilization services.
This was not the case before—cGMP compliance now is being pushed by the FDA and starting to take hold among leading compounding pharmacies. “Some pharmacies have already been closed down or received warning letters,” said Prince. “As a testing organization, we are helping this industry learn how to meet the challenges that are already familiar to pharmaceutical and medical device companies.”
OEMs also are putting more pressure on contract testers to control or reduce costs, as well as deliver faster turnaround times on testing. Finding the extra efficiencies to accomplish these goals can be very challenging, especially with tests that require specific amounts of time. Contract testers also are receiving more “just-in-time” requests for testing—meaning customers are asking for much shorter lead times to get things done.
“For example, medical device companies are cutting back on support staff, such as in the packaging function, resulting in more projects being requested at the last minute,” said Patrick J. Nolan, president of DDL Inc., an Eden Prairie, Minn.-based medical device testing laboratory that specializes in package, product and material testing services. “We are also working with less-experienced packaging personnel, who need our help to understand the regulations.”
Regulators also require that test labs validate the test methods they are performing. Labs must show that tests are reliable and repeatable. There also is more scrutiny by regulators on packaging, with ISO 11607 being the standard they follow for compliance. As a result, an increasing number of OEMs are asking for validated testing methods.
“There is also much more emphasis on process control for the equipment used to perform the testing,” added Corey Hensel, general manager for DDL. “This allows for the same reproducible and repeatable results each time a test is performed.”
Materials Characterization
Contract testers are seeing more requests from OEMs for materials characterization testing for medical devices and materials. Both regulatory agencies and medical device companies seek more data to better understand how their products will perform.
“For example, more companies are choosing to follow up cytotoxicity failures with chemical evaluations of the extract to determine what is causing the problem,” said Lisa Olson, vice president for testing and service development for WuXi AppTec, a St. Paul, Minn.-based contract testing service for medical devices.
For more routine characterization, she noted, manufacturers of infusion and tubing sets now are performing baseline chemical evaluations much earlier in the development process than before. “Traditionally, they have waited until the very end to do bare minimums for testing,” she said. “Now we are seeing greater interest in identifying any problems early.”
Extractables/leachables testing has largely been focused on metals and colorants. Although a particular colorant may have been used successfully for some time, an OEM might want to utilize that colorant in a different way for its devices. If so, this creates a new risk for the type of human contact that must be addressed.
“The challenge is not so much the actual testing of these materials, but designing the right conditions to determine the potential for metals or colorants to leach from the devices in simulated-use and worst-case scenarios,” said Olson. “Doing chemistry work with that paradigm presents some unique challenges to the chemists, because unlike pure chemicals, polymers frequently have many unknown chemicals that must be evaluated—and these are what regulatory agencies have been particularly concerned about recently.”
Biocompatibility Testing
2013 was a strong year for biocompatibility testing of medical devices, as well as sterility assurance testing. There also was a greater push to have analytical methods—especially chemical characterization—support biocompatibility testing. The primary driver for this trend is regulatory concern.
“The FDA has begun asking for analytical, chemical characterization data to complement in vivo study data, for devices with the potential for long systemic contact periods,” commented Aaron Burke, director of business development for Pacific BioLabs, a Hercules, Calif.-based provider of preclinical testing and quality-control support testing for multiple industries. “These devices have a greater possibility of leaching something out into the body because of the long contact period. The analytical data may discover a potential for harm not fully detected by the in-vivo studies.”
Tying biocompatibility data and chemical analyses into a cohesive story that demonstrates the safety of a medical device is leading to more customer requests for risk assessments, gap analyses and testing summaries. A few years ago, submission packages consisted of a series of reports, data files, specifications and drawings that simply were sent to the FDA with a 510(k) cover letter. Now the FDA also expects risk assessments and biological evaluations.
“When our clients ask for help with this, we are typically writing biological evaluations that summarize the device, its use and potential risks and an evaluation and interpretation of all of the available data,” said Olson. “Basically, we are creating a single document that helps explain the significant amount of work that went into the chemistry and safety testing.”
The second big driver for collecting analytical data on medical devices is saving money. Currently, any slight change to a device—even just a slight manufacturing process or colorant change—requires an in vivo biocompatibility study to ensure the change does not negatively affect the overall biocompatibility of the device.
“However,” said Burke, “if the device has been previously analytically characterized with the old colorant or manufacturing process, then we can analytically examine the device after the change and compare the two. If there are no major differences, we can classify them as equivalent without the need for in-vivo biocompatibility studies. This saves both time and money, as well as reduces the use of animals in testing.”
New FDA guidance also will impact biocompatibility. Although largely harmonized with ISO 10993, the April 2013 draft guidance document calls for changes in requirements for implants and orthopedics. This may include routine endotoxin testing for implantable devices, updates to hemocompatibility study requirements and more requirements for the evaluation of materials (including colorants).
“The new guidance very clearly indicates that prior to initiating long-term implant or custom biocompatibility studies, OEMs should draft the study design protocol and review with the FDA to receive input,” advised John S. Bolinder, chief strategy officer for Nelson Laboratories Inc., a Salt Lake City, Utah-based provider of microbiological and analytical test services for medical device manufacturers. “This change indicates the agency is partnering more with industry to establish valid study designs.”
Industry comments on the draft guidance have been submitted and a revised draft or final guidance is expected later this year.
Human Factors Testing
Many medical device companies believe testing human factors is for market research only and not important for improving medical device design and function. However, human factors issues often are cited by the FDA as submission areas that need strengthening before filing. Relying only on instructions for use to reduce risk is costly, time consuming and not a guaranteed method to reduce risk. It is better over the long term to incorporate human factors as early as possible, which also reduces development time and cost.
“The field of human factors in healthcare is expanding rapidly, with many companies rushing into this space,” said Reade Harpham, director of human centric design for Battelle, a Columbus, Ohio-based independent research and development industry that conducts human factors testing for several industries. “Many of our long-term medical device clients have human factors as a line item in their budgets and are able to fund the work at appropriate levels, along with other risk-mitigation activities.”
Clinical usability is another key aspect of human factors testing. Battelle is fielding more requests from clients to study critical tasks ill-suited for simulation, such as actual injection into or application onto the skin. The simulation must be accurate enough to capture all likely use errors.
“For example, the way people use a pen injector may differ greatly if they know they will be injecting themselves, instead of a practice injection pad,” noted Harpham. “Even though it is not required by the FDA, the agency wants to ensure that testing scenarios are representative of real use and appropriately address the likely risks. Because we are testing usability, and not efficacy, the devices are filled with placebo, but still run with clinical oversight.”
In addition, human factors are important for designing a training protocol for final products. A person trained to use a particular device may not use it right away—for example, a patient prescribed and trained to use a pen injector will, at a minimum, have a delay between that time, picking up the prescription at the pharmacy and then doing the injection. For devices used on an “as needed” basis, weeks or months might pass before people first need or use the product.
“To address this risk, the FDA would like to see some representative period of time included in the study design to account for or simulate the training/memory decay between the anticipated ‘real-life’ training and first use,” said David F. Wourms, a senior research scientist for Battelle. “This time period can be compressed somewhat and still be representative. Studies could include anywhere from one hour to two weeks or more between the time training is provided and data is collected.”
Counterfeit Component Testing
More OEMs are concerned about counterfeit components. Counterfeiting becomes profitable when scrapped components, recycled product parts or inexpensive components are “remarked” and sold as new, more expensive, higher-reliability versions. Reasons for the proliferation of counterfeiting include the exporting of U.S. electronic waste for disposal in poorer countries.
“Much of the overall effort today is spent on screening components to identify and remove counterfeits before they are used in a finished product, rather than preventing counterfeiting,” said John Radman, senior technical director at Trace Laboratories, a Hunt Valley, Md.-based full-service testing laboratory that provides a variety of testing, including counterfeit component screening.
The greatest threat lies in the purchase of non-original component manufactured parts. Screening a typical lot of parts (less than 200 components) costs between $800 and $2,000, depending on if the screening is conducted using visual methods or destructive analysis.
“Visual examination is the simplest and quickest of the inspection techniques, requiring just an optical microscope, a few chemicals and a trained eye,” said Radman. An experienced inspector can identify sanding marks, blacktopping, evidence of rework, bent leads, replated leads, definition and quality of markings, appropriate markings and logos and alteration of the originally occurring features on a component. Other techniques include electrical inspection, X-ray inspection, scanning electron microscopy and X-ray fluorescence.
Expanded Capabilities
Medical device companies want to work with contract testers that provide an ever-expanding array of capabilities. To remain preferred vendors, contract testers are providing more services. For example, DDL has included more protocols for testing packaging, chamber mapping and temperature stability testing for compliance to ICH standards.
Polymer Solutions has developed an internal method for determining the molecular weight for polyetheretherketone (PEEK) material. By testing molecular weight, an engineer can determine if the manufacturing process has altered the material in the final product. The analytical department at Pacific BioLabs has been exploring novel ways to use the sensitivity of inductively coupled plasma mass ICP-MS to measure drug or drug metabolite levels of metal-containing drugs in pharmacokinetic samples. WuXi AppTec also has expanded many of its chemistry and microbiology services, including the number of quantitative endpoints it uses in its cleaning and reprocessing validations.
Eliminating animal testing is gaining momentum in the United States. As a result, Nelson Laboratories has expanded its analytical ISO 10993-17 and 10993-18 material characterization services to help assess material, adhesive or other product changes using analytical methods and written justifications that could substitute for animal testing. The company also has validated in-vitro irritation assays and is currently running comparative pilot studies with client products to move away from animal testing.
“We are hopeful the FDA will begin accepting in-vitro irritation and in-vitro sensitization studies for surface contacting medical devices (Class I and II) in the near future,” said Bolinder. “Most in-vivo irritation studies have passing results and the in-vitro irritation models are more consistent and appear to be more sensitive.”
Another upcoming regulatory change likely will impact testing standards for automated external defibrillators (AED) and accessories (IEC 60601-2-4).
Compliance West USA, a San Diego, Calif.-based manufacturer of testers for defibrillators, is receiving more requests from clients for a biphasic tester to conduct the energy measurement tests in preparation for the FDA’s expected ruling that will require pre-market approval for AEDs and accessories. A biphasic tester can cost as much as $18,000.
“For products that require only one-off testing, we have engineered a biphasic tester on the bench,” said Jeff Lind, president of Compliance West USA. “Underwriters Laboratories plans to send an engineer to validate the bench tester and witness the testing. If approved, we can provide these special tests on the bench at a great savings for manufacturers who need to do the test just once, compared to purchasing the biphasic tester.”
Trace Laboratories has added additional environmental simulation chambers to handle the growing demand in ultraviolet (UV), xenon arc, temperature/humidity and thermal shock testing. Sunlight, heat and moisture cause millions of dollars of product damage every year such as fading, color change, strength loss, cracking, crazing and reduced gloss.
“The chambers can be used to simulate and accelerate indoor and outdoor service conditions,” said Radman. “Xenon lamps in the chamber provide the most realistic simulation of full-spectrum sunlight, including UV, visible and infrared wavelengths. We also have the ability to add a water-spray cycle for thermal shock and mechanical erosion.”
Gibraltar Laboratories has built a new state-of-the-art laboratory to provide glass vials that are clean, depyrogenated and suitable for parenteral use. Sophisticated equipment includes large steam sterilizers, water for injection systems and vial and stopper washers. Air-over pressure steam sterilization can be used for prefilled syringes and for various liquids in sealed glass vessels. The lab also will provide testing services such as bacterial endotoxin testing and sterility testing. Although Gibraltar stays busy as a primary source for sterilization services, it also has the capacity and response time to serve as a backup provider as well.
“We are positioned to serve as a source to assure business continuity for companies that may be affected by supply chain or vendor issues,” said Prince. “For example, Superstorm Sandy showed manufacturers how critical it is to have back-up and redundancy plans, in the event of large-scale disruptions.”
Find Your Partner
OEMs aggressively are shortening their supply chains and looking for partners that provide multiple services and are eager to help with achieving the goals of higher quality, lower cost and regulatory compliance. Being this kind of collaborative partner requires agility, good communication, and a significant level of trust.
“The contract testing laboratory is an extension of the client and should take into account the quality of the client’s organization,” said Prince. “It is important that the client and contract testing laboratory develop a collaborative relationship that enables the development of cost-effective solutions, as well as realistic timelines that can be met.”
Testing often is forgotten about during the design process, which can be a costly mistake.
“By using a testing lab early in a product development stage, the end result is often the elimination of material problems and a reduction in the approval process for a device,” said George Cheynet, sales director for Polymer Solutions. He noted that about three-quarters of medical device manufacturers do not use testing labs early enough in the process. Now, however, larger OEMs are starting to incorporate testing and validation earlier in the R&D process. In contrast, startup companies tend not to use contract testing labs early due to lack of R&D and regulatory submission experience, or cash flow.
Bolinder agreed.
“We see many small and midsize companies with limited resources, that have incredibly talented engineers and quality personnel, but fail to design for sterilization, packaging or reuse of a new device,” he said. “Unfortunately, this often occurs after extensive expenditure by the manufacturer with a working prototype, or nearly finished product, who then must go back to do further design review. This can result in significant delays to regulatory and marketing approval.”
In response, Nelson Laboratories has expanded its training and consulting services to make its scientific staff available for consultation during the critical design stages. “This helps clients anticipate what’s next and whether a design or material change will have downstream impacts,” said Bolinder.
Device manufacturers must trust their contract manufacturers as partners. Yet Olson regularly sees that, despite legal contracts for confidentiality and IP protection, many manufacturers are reluctant to share design details and specifications, including the materials in use.
“For example,” said Olson, “sharing with the testing laboratory that an antimicrobial is used in the device can prevent a lot of false positive results, because assays can be designed to take that known toxicity into account. Contract testers are only asking detailed, probing questions so they can provide the best possible advice and testing strategy for their clients.”
Basically, developing a deep OEM-contract tester relationship improves quality, speeds up time to market, and reduces costs.
“In this marketplace, time is money,” concluded Cheynet. “If you can eliminate every question in the submission process and get your product into the marketplace faster than your competition, the return can be hundreds of thousands of dollars or more—and testing is a critical step in making that happen.”
Mark Crawford is a full-time freelance business, marketing and communications writer based in Madison, Wis. He can be reached at mark.crawford@charter.net.
Some such demands are driven by evolving regulations such as a revised version of the European Union’s Restriction of Hazardous Substances directive (RoHS II), which takes effect this summer and impacts medical device testing requirements.
Another regulation is U.S. Pharmacopeial Convention (USP) 661, which will require inductively coupled plasma mass spectrometry (ICP-MS) characterization of plastics. More medical OEMs also are auditing their contract testers to ISO 17025 standards instead of current Good Manufacturing Practice (cGMP) compliance.
“The FDA (U.S. Food and Drug Administration) uses risk to categorize which companies get audited and how frequently,” said Megan Evans, technical quality lead for Polymer Solutions Inc., a Blacksburg, Va.-based testing lab that provides chemical, material and analytical testing for the medical industry. “In response, we are applying more risk-based approaches toward client-specific method validations and changes to equipment, instrumentation and our facility in accordance with ICH Q9, a guidance document published by the International Conference on Harmonization (ICH) on Quality Risk Management.”
A high-risk area currently getting lots of FDA attention is compounding pharmacies and sterile injectables (driven in part by recent deaths related to products contaminated with fungal meningitis).
“This industry as a whole is adjusting to increased validation and testing to assure their sterile injectable drugs are safe for patient use,” said Daniel Prince, president of Gibraltar Laboratories Inc., a Fairfield, N.J.-based provider of chemical and biological testing and steam sterilization services.
This was not the case before—cGMP compliance now is being pushed by the FDA and starting to take hold among leading compounding pharmacies. “Some pharmacies have already been closed down or received warning letters,” said Prince. “As a testing organization, we are helping this industry learn how to meet the challenges that are already familiar to pharmaceutical and medical device companies.”
OEMs also are putting more pressure on contract testers to control or reduce costs, as well as deliver faster turnaround times on testing. Finding the extra efficiencies to accomplish these goals can be very challenging, especially with tests that require specific amounts of time. Contract testers also are receiving more “just-in-time” requests for testing—meaning customers are asking for much shorter lead times to get things done.
“For example, medical device companies are cutting back on support staff, such as in the packaging function, resulting in more projects being requested at the last minute,” said Patrick J. Nolan, president of DDL Inc., an Eden Prairie, Minn.-based medical device testing laboratory that specializes in package, product and material testing services. “We are also working with less-experienced packaging personnel, who need our help to understand the regulations.”
Regulators also require that test labs validate the test methods they are performing. Labs must show that tests are reliable and repeatable. There also is more scrutiny by regulators on packaging, with ISO 11607 being the standard they follow for compliance. As a result, an increasing number of OEMs are asking for validated testing methods.
“There is also much more emphasis on process control for the equipment used to perform the testing,” added Corey Hensel, general manager for DDL. “This allows for the same reproducible and repeatable results each time a test is performed.”
Materials Characterization
Contract testers are seeing more requests from OEMs for materials characterization testing for medical devices and materials. Both regulatory agencies and medical device companies seek more data to better understand how their products will perform.
“For example, more companies are choosing to follow up cytotoxicity failures with chemical evaluations of the extract to determine what is causing the problem,” said Lisa Olson, vice president for testing and service development for WuXi AppTec, a St. Paul, Minn.-based contract testing service for medical devices.
For more routine characterization, she noted, manufacturers of infusion and tubing sets now are performing baseline chemical evaluations much earlier in the development process than before. “Traditionally, they have waited until the very end to do bare minimums for testing,” she said. “Now we are seeing greater interest in identifying any problems early.”
Extractables/leachables testing has largely been focused on metals and colorants. Although a particular colorant may have been used successfully for some time, an OEM might want to utilize that colorant in a different way for its devices. If so, this creates a new risk for the type of human contact that must be addressed.
“The challenge is not so much the actual testing of these materials, but designing the right conditions to determine the potential for metals or colorants to leach from the devices in simulated-use and worst-case scenarios,” said Olson. “Doing chemistry work with that paradigm presents some unique challenges to the chemists, because unlike pure chemicals, polymers frequently have many unknown chemicals that must be evaluated—and these are what regulatory agencies have been particularly concerned about recently.”
Biocompatibility Testing
2013 was a strong year for biocompatibility testing of medical devices, as well as sterility assurance testing. There also was a greater push to have analytical methods—especially chemical characterization—support biocompatibility testing. The primary driver for this trend is regulatory concern.
“The FDA has begun asking for analytical, chemical characterization data to complement in vivo study data, for devices with the potential for long systemic contact periods,” commented Aaron Burke, director of business development for Pacific BioLabs, a Hercules, Calif.-based provider of preclinical testing and quality-control support testing for multiple industries. “These devices have a greater possibility of leaching something out into the body because of the long contact period. The analytical data may discover a potential for harm not fully detected by the in-vivo studies.”
Tying biocompatibility data and chemical analyses into a cohesive story that demonstrates the safety of a medical device is leading to more customer requests for risk assessments, gap analyses and testing summaries. A few years ago, submission packages consisted of a series of reports, data files, specifications and drawings that simply were sent to the FDA with a 510(k) cover letter. Now the FDA also expects risk assessments and biological evaluations.
“When our clients ask for help with this, we are typically writing biological evaluations that summarize the device, its use and potential risks and an evaluation and interpretation of all of the available data,” said Olson. “Basically, we are creating a single document that helps explain the significant amount of work that went into the chemistry and safety testing.”
The second big driver for collecting analytical data on medical devices is saving money. Currently, any slight change to a device—even just a slight manufacturing process or colorant change—requires an in vivo biocompatibility study to ensure the change does not negatively affect the overall biocompatibility of the device.
“However,” said Burke, “if the device has been previously analytically characterized with the old colorant or manufacturing process, then we can analytically examine the device after the change and compare the two. If there are no major differences, we can classify them as equivalent without the need for in-vivo biocompatibility studies. This saves both time and money, as well as reduces the use of animals in testing.”
New FDA guidance also will impact biocompatibility. Although largely harmonized with ISO 10993, the April 2013 draft guidance document calls for changes in requirements for implants and orthopedics. This may include routine endotoxin testing for implantable devices, updates to hemocompatibility study requirements and more requirements for the evaluation of materials (including colorants).
“The new guidance very clearly indicates that prior to initiating long-term implant or custom biocompatibility studies, OEMs should draft the study design protocol and review with the FDA to receive input,” advised John S. Bolinder, chief strategy officer for Nelson Laboratories Inc., a Salt Lake City, Utah-based provider of microbiological and analytical test services for medical device manufacturers. “This change indicates the agency is partnering more with industry to establish valid study designs.”
Industry comments on the draft guidance have been submitted and a revised draft or final guidance is expected later this year.
Human Factors Testing
Many medical device companies believe testing human factors is for market research only and not important for improving medical device design and function. However, human factors issues often are cited by the FDA as submission areas that need strengthening before filing. Relying only on instructions for use to reduce risk is costly, time consuming and not a guaranteed method to reduce risk. It is better over the long term to incorporate human factors as early as possible, which also reduces development time and cost.
“The field of human factors in healthcare is expanding rapidly, with many companies rushing into this space,” said Reade Harpham, director of human centric design for Battelle, a Columbus, Ohio-based independent research and development industry that conducts human factors testing for several industries. “Many of our long-term medical device clients have human factors as a line item in their budgets and are able to fund the work at appropriate levels, along with other risk-mitigation activities.”
Clinical usability is another key aspect of human factors testing. Battelle is fielding more requests from clients to study critical tasks ill-suited for simulation, such as actual injection into or application onto the skin. The simulation must be accurate enough to capture all likely use errors.
“For example, the way people use a pen injector may differ greatly if they know they will be injecting themselves, instead of a practice injection pad,” noted Harpham. “Even though it is not required by the FDA, the agency wants to ensure that testing scenarios are representative of real use and appropriately address the likely risks. Because we are testing usability, and not efficacy, the devices are filled with placebo, but still run with clinical oversight.”
In addition, human factors are important for designing a training protocol for final products. A person trained to use a particular device may not use it right away—for example, a patient prescribed and trained to use a pen injector will, at a minimum, have a delay between that time, picking up the prescription at the pharmacy and then doing the injection. For devices used on an “as needed” basis, weeks or months might pass before people first need or use the product.
“To address this risk, the FDA would like to see some representative period of time included in the study design to account for or simulate the training/memory decay between the anticipated ‘real-life’ training and first use,” said David F. Wourms, a senior research scientist for Battelle. “This time period can be compressed somewhat and still be representative. Studies could include anywhere from one hour to two weeks or more between the time training is provided and data is collected.”
Counterfeit Component Testing
More OEMs are concerned about counterfeit components. Counterfeiting becomes profitable when scrapped components, recycled product parts or inexpensive components are “remarked” and sold as new, more expensive, higher-reliability versions. Reasons for the proliferation of counterfeiting include the exporting of U.S. electronic waste for disposal in poorer countries.
“Much of the overall effort today is spent on screening components to identify and remove counterfeits before they are used in a finished product, rather than preventing counterfeiting,” said John Radman, senior technical director at Trace Laboratories, a Hunt Valley, Md.-based full-service testing laboratory that provides a variety of testing, including counterfeit component screening.
The greatest threat lies in the purchase of non-original component manufactured parts. Screening a typical lot of parts (less than 200 components) costs between $800 and $2,000, depending on if the screening is conducted using visual methods or destructive analysis.
“Visual examination is the simplest and quickest of the inspection techniques, requiring just an optical microscope, a few chemicals and a trained eye,” said Radman. An experienced inspector can identify sanding marks, blacktopping, evidence of rework, bent leads, replated leads, definition and quality of markings, appropriate markings and logos and alteration of the originally occurring features on a component. Other techniques include electrical inspection, X-ray inspection, scanning electron microscopy and X-ray fluorescence.
Expanded Capabilities
Medical device companies want to work with contract testers that provide an ever-expanding array of capabilities. To remain preferred vendors, contract testers are providing more services. For example, DDL has included more protocols for testing packaging, chamber mapping and temperature stability testing for compliance to ICH standards.
Polymer Solutions has developed an internal method for determining the molecular weight for polyetheretherketone (PEEK) material. By testing molecular weight, an engineer can determine if the manufacturing process has altered the material in the final product. The analytical department at Pacific BioLabs has been exploring novel ways to use the sensitivity of inductively coupled plasma mass ICP-MS to measure drug or drug metabolite levels of metal-containing drugs in pharmacokinetic samples. WuXi AppTec also has expanded many of its chemistry and microbiology services, including the number of quantitative endpoints it uses in its cleaning and reprocessing validations.
Eliminating animal testing is gaining momentum in the United States. As a result, Nelson Laboratories has expanded its analytical ISO 10993-17 and 10993-18 material characterization services to help assess material, adhesive or other product changes using analytical methods and written justifications that could substitute for animal testing. The company also has validated in-vitro irritation assays and is currently running comparative pilot studies with client products to move away from animal testing.
“We are hopeful the FDA will begin accepting in-vitro irritation and in-vitro sensitization studies for surface contacting medical devices (Class I and II) in the near future,” said Bolinder. “Most in-vivo irritation studies have passing results and the in-vitro irritation models are more consistent and appear to be more sensitive.”
Another upcoming regulatory change likely will impact testing standards for automated external defibrillators (AED) and accessories (IEC 60601-2-4).
Compliance West USA, a San Diego, Calif.-based manufacturer of testers for defibrillators, is receiving more requests from clients for a biphasic tester to conduct the energy measurement tests in preparation for the FDA’s expected ruling that will require pre-market approval for AEDs and accessories. A biphasic tester can cost as much as $18,000.
“For products that require only one-off testing, we have engineered a biphasic tester on the bench,” said Jeff Lind, president of Compliance West USA. “Underwriters Laboratories plans to send an engineer to validate the bench tester and witness the testing. If approved, we can provide these special tests on the bench at a great savings for manufacturers who need to do the test just once, compared to purchasing the biphasic tester.”
Trace Laboratories has added additional environmental simulation chambers to handle the growing demand in ultraviolet (UV), xenon arc, temperature/humidity and thermal shock testing. Sunlight, heat and moisture cause millions of dollars of product damage every year such as fading, color change, strength loss, cracking, crazing and reduced gloss.
“The chambers can be used to simulate and accelerate indoor and outdoor service conditions,” said Radman. “Xenon lamps in the chamber provide the most realistic simulation of full-spectrum sunlight, including UV, visible and infrared wavelengths. We also have the ability to add a water-spray cycle for thermal shock and mechanical erosion.”
Gibraltar Laboratories has built a new state-of-the-art laboratory to provide glass vials that are clean, depyrogenated and suitable for parenteral use. Sophisticated equipment includes large steam sterilizers, water for injection systems and vial and stopper washers. Air-over pressure steam sterilization can be used for prefilled syringes and for various liquids in sealed glass vessels. The lab also will provide testing services such as bacterial endotoxin testing and sterility testing. Although Gibraltar stays busy as a primary source for sterilization services, it also has the capacity and response time to serve as a backup provider as well.
“We are positioned to serve as a source to assure business continuity for companies that may be affected by supply chain or vendor issues,” said Prince. “For example, Superstorm Sandy showed manufacturers how critical it is to have back-up and redundancy plans, in the event of large-scale disruptions.”
Find Your Partner
OEMs aggressively are shortening their supply chains and looking for partners that provide multiple services and are eager to help with achieving the goals of higher quality, lower cost and regulatory compliance. Being this kind of collaborative partner requires agility, good communication, and a significant level of trust.
“The contract testing laboratory is an extension of the client and should take into account the quality of the client’s organization,” said Prince. “It is important that the client and contract testing laboratory develop a collaborative relationship that enables the development of cost-effective solutions, as well as realistic timelines that can be met.”
Testing often is forgotten about during the design process, which can be a costly mistake.
“By using a testing lab early in a product development stage, the end result is often the elimination of material problems and a reduction in the approval process for a device,” said George Cheynet, sales director for Polymer Solutions. He noted that about three-quarters of medical device manufacturers do not use testing labs early enough in the process. Now, however, larger OEMs are starting to incorporate testing and validation earlier in the R&D process. In contrast, startup companies tend not to use contract testing labs early due to lack of R&D and regulatory submission experience, or cash flow.
Bolinder agreed.
“We see many small and midsize companies with limited resources, that have incredibly talented engineers and quality personnel, but fail to design for sterilization, packaging or reuse of a new device,” he said. “Unfortunately, this often occurs after extensive expenditure by the manufacturer with a working prototype, or nearly finished product, who then must go back to do further design review. This can result in significant delays to regulatory and marketing approval.”
In response, Nelson Laboratories has expanded its training and consulting services to make its scientific staff available for consultation during the critical design stages. “This helps clients anticipate what’s next and whether a design or material change will have downstream impacts,” said Bolinder.
Device manufacturers must trust their contract manufacturers as partners. Yet Olson regularly sees that, despite legal contracts for confidentiality and IP protection, many manufacturers are reluctant to share design details and specifications, including the materials in use.
“For example,” said Olson, “sharing with the testing laboratory that an antimicrobial is used in the device can prevent a lot of false positive results, because assays can be designed to take that known toxicity into account. Contract testers are only asking detailed, probing questions so they can provide the best possible advice and testing strategy for their clients.”
Basically, developing a deep OEM-contract tester relationship improves quality, speeds up time to market, and reduces costs.
“In this marketplace, time is money,” concluded Cheynet. “If you can eliminate every question in the submission process and get your product into the marketplace faster than your competition, the return can be hundreds of thousands of dollars or more—and testing is a critical step in making that happen.”
Mark Crawford is a full-time freelance business, marketing and communications writer based in Madison, Wis. He can be reached at mark.crawford@charter.net.