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Many medical devices, including surgical tools, cutting templates, trial devices, and long term implants, are produced using additive manufacturing technology via the powder bed fusion (PBF) process. PBF offers a significant benefit in medical device production by enabling the creation of highly customized and patient-specific solutions.

PBF in Medical Device Manufacture

However, this unique manufacturing process has features that require specific characterization to ensure safety and biocompatibility. PBF often results in residual powder, which is hard to remove even with the use of post processing. Powdered material on the finished device could have clinical significance depending on the quantity of powder and anatomical location of the device.

The surface texture of PBF parts can vary greatly, ranging from rough and porous to smooth and dense. The surface finish can have a significant impact on the biocompatibility and the performance of the device. Additionally, the surface finish can affect the wear characteristics and potential for corrosion or delamination. Surface characterization of the PBF process is essential to ensure the safety and efficacy of the device.

ASTM Standards for Medical Devices Made by Additive Manufacturing

ASTM is working on standards to assess residual powder on medical devices. ASTM F3335 (Standard guide for assessing the removal of residues from medical devices made by powder bed fusion) has been available for a few years. ASTM is working on a supplementary test method standard for assessing residual powder (working item WK82776).

Another standard released by ASTM is F3456, which outlines how AM manufactures will reuse unused powder so they can report this process to regulators. ASTM is also working on a guide for material process validation in AM manufactured parts (WK72659).

These standards will help ensure the safety and efficacy of AM manufactured medical devices and provide guidance for manufacturers. This guidance is critical for the development and commercialization of AM-manufactured medical devices.

Contact our material science experts for testing and validation in support of your additive manufactured products.

Committee F04 on Medical Devices sponsored a workshop on discussion setting limits for residues on medical devices during cleaning validation on May 9, 2023 in Denver, CO. The conference was organized by Stephen Spiegelberg (Cambridge Polymer Group) and Ralph Basile (Healthmark), and included presenters from testing laboratories, device manufacturers, material manufacturers, regulators, toxicologists, and cleaning consultants.

Randy Thoma (Veeasquared) presented a historical perspective on the Sulzer Interop recall in the early 2000s, which prompted the formation of the cleaning task group in ASTM. Jeff Rufner and Ben Grosjean (Zimmer) discussed how to leverage residues in clinically-successful devices in establishing acceptance limits. Allan Kimble (J&J) focused his talk on test methods and their suitability towards patient safety. 

Becky Bader (Cambridge Polymer Group) presented a summary of standards related to particulate levels and measurement techniques and gaps in this standardization. A presentation by Daniel Curtin (Edwards Lifesciences) focused on designing a cleaning validation approach for multi-component cleaning processes. Boopathy Dhanapal presented the current information on ISO standards related to cleaning and levels. Clement Cremmel (Ultraschall) described ultrasonic cleaning and examples of establishing limits in cleaning metallic devices. Reto Luginbuehl (Blaser) described chemical deformation of lubricants and the use of toxicology data to determine limits. Barbara and Ed Kanegsberg (BFK) talked about cleaning standards. 

In the afternoon, Isaac Mohar (Gradient) discussed how toxicology is used to establish limits, which was continued in the next talk by Robert Mueller (Nelson Labs), who presented on the use of ISO 10993-18/17 for establishing limits. Terra Kremer (J&J) led a discussion on the using of the Spaulding classification system to establish limits for re-usable devices. The discussion of re-usables continued with a talk about cleaning dental products by Spiro Megremis (ADA Science and Research Institute), and a study of test soils for cleaning validation by Stephen Morris (Stryker).

The day finished with a talk by Terry Woods (FDA) on the FDA’s use and reliance on standards, followed by a group discussion of gaps in standards and the need for additional standards related to setting limits. This work will be conducted within task group F04.15.17.

CPG consults with clients on a regular basis in cleaning assessment and validation.  Contact us for more information on how we can help you.

The Environmental Protection Agency (EPA) is proposing new standards on chemicals used to sterilize medical devices, including ethylene oxide (EO/EtO), one of the more commonly used sterilants. However, ethylene oxide has recently been scrutinized due to safety concerns about workers' EtO exposure at sterilization facilities.

The EPA is proposing a decrease in the highest allowable airborne concentration of ethylene oxide. The proposed level of EtO is 0.2 parts per million (ppm), which is lower than the current standard of 1 ppm.

This proposed standard is based on recent research that suggests that long-term exposure to an amount of EtO greater than 0.2 ppm can be hazardous to human health. The EPA also proposes that sterilization facilities must implement rigorous monitoring and reporting protocols to ensure the safety of workers and surrounding communities.

Although ethylene oxide is a toxic gas, it is an effective sterilant for many medical devices that cannot be sterilized by ionizing radiation (gamma, e-beam, or X-ray) or through steam autoclaves, due to the polymer composition of these devices.

Some trade associations are concerned about the EPA's proposal. They believe the safety requirements will take longer than 18 months to put into place. A slowdown of EtO sterilization could affect the supply chain of billions of medical devices per year, negatively impacting patients' access to health care.

Consider Alternative Sterilization Modalities

This slowdown may push device manufacturers to consider other sterilization modalities. CPG has expertise in radiation chemistry of polymers, as well as how temperature can affect these materials, and can assist clients in developing and validating appropriate sterilization processes for medical devices.

Medical device manufacturers who make changes in their sterilization method, process or facility outlined in their original Premarket Approval must submit a PMA supplement so that the FDA can review the changes. 510(k) holders would need to consult FDA guidance on whether a change in sterilization modality on their device would require a new 510(k) submission.

CPG's team of materials experts can explain the complexities of the sterilization process and provide guidance on the best options to meet regulatory requirements. We can help clients evaluate sterilization modalities, and if a change in the sterilization method is required, we can provide support in filing the appropriate PMA supplement or 510(k).

Our polymer scientists can provide answers to any questions you may have and offer a comprehensive plan to ensure your medical device is compliant with FDA requirements. Contact one of our scientists today for a consultation.

Registration is open for ASTM International’s Workshop on Setting Acceptance Limits for Cleaning Validation of Medical Devices, to be held May 9, 2023 at the Sheraton Denver Downtown Hotel (Denver, Colorado, USA). The event is sponsored by ASTM’s medical and surgical materials and devices committee (F04) and will be held in conjunction with the May standards development meetings of the committee.

This workshop will identify current best practices in setting acceptance limits in cleaning of medical devices, gaps in standardization of this practice, and areas where new standards would be useful. Considerations include crossover with ISO 10993 standards and potential updates to these requirements.

Topics include, but are not limited to:

• Case studies of cleaning with issues associated with acceptance limits;
• Current standards on cleaning of medical devices;
• Types of residues and considerations;
• Methods for establishing acceptance limits;
• Approaches for using acceptance limits in cleaning validation;
• When to modify acceptance limits;
• Approaches to limit establishment when there is a change in manufacturing process;
• Gaps in acceptance limits guidance;
• Pharmaceutical manufacturer position on acceptance limits;
• Regulatory perspective on setting limits and rationale; and
• Development of proposal(s) for development of new ASTM standards related to acceptance limits for medical devices.

Additional information is available from the workshop’s technical chairs, Stephen Spiegelberg (stephen.spiegelberg@campoly.com) and Ralph Basile (rbasile@healthmark.com).

To register for the event or for more information, visit https://go.astm.org/cleaning-validation-workshop.

Symposia Operations Contact: Tammy Schane, tel+1.610.832.9522, symposia@astm.org

At the end of January, Scots and poetry lovers around the world gather to celebrate the birthday of Scotland’s most famous poet, Robert (or Rabbie) Burns. Burns Night guests sit at long tables sipping Scotch while the haggis is paraded about the room, followed by a bagpiper playing musical tribute to Scotland’s traditional Haggis. Burns’ “Address to a Haggis” is recited and then the pudding is served.  For those less adventurous there are even excellent vegetarian options available!

An integral part of the celebration is the liberal application of whisky.  For many people, this is more important than the poetry!  Whisky is Scotland’s official national drink (though IRN BRU may beg to differ), and Burns’ poetry is filled with whisky references. In “Scotch Drink,” Burns credits whisky as his muse and inspiration.  In “Tam o’ Shanter,” he says that the “water of life” inspires devil-facing powers, and in “The Author’s Earnest Cry and Prayer,” he equates freedom with whisky.

As our own tribute to Burns’ self-proclaimed inspiration, Cambridge Polymer Group performed some chromatographic analysis on a number of single malt Scotches from the Highlands, Arran, Islay and Speyside.

Although there are few discernable patterns in the Gas Chromatography data, some qualitative trends are observed. Furfural, Hexanoic acid and 1-Butanol are largely present in all samples. The p-Cresol appears more associated with the Spey whiskies, and the o-Cresol appears more associated with the Islay whiskies. In terms of the three different aged whiskies (-15, -16 and -17, from Arran), there is no compound that appears to rank with age. Reviewing the Head Space Gas Chromatography data, the compounds that one would expect to provide the closest match to the drinker’s initial perception of the whisky yields a similar result, with no clear pattern emerging.

Our initial hope of teasing out simple correlations with known traits of the whiskies was not borne out.  At least partially this is due to the intrinsic complexity of these liquids, with combinations of age, processing, environment and ingredients resulting in a complexity that is difficult to handle analytically.  In addition, most of the liquids presented here are in fact blended from multiple barrels (even though they are termed “single malts”) to create a certain profile, further complicating any analytical process. 

This study was an internal project, conducted to demonstrate some of CPG’s chromatographic abilities without compromising any confidential client data and as an excuse to hold a whisky tasting with leftover supplies. When CPG analyzes a product on behalf of a client, we have access to the manufacturer’s IP (including key information about processing, environment, and materials), which allows us to better isolate compound correlations with known traits.

Complexity is increasingly becoming the norm in analytical chemistry. CPG conducts complex profiles in Extractable and Leachable (E&L) studies in support of biocompatibility determinations, and for new medical devices and drugs requiring analysis in vivo for residual products or change products. However, because we keep our clients’ IP confidential, we can’t share most of those examples (unless our client has given permission or credited us in publication).  CPG is very proud of our part in a cancer study, in which we performed a complex direct analysis of physiological fluids for analytes generated by the body (which we can discuss because our participation was published by our client). 

Although the hoped-for patterns were not found in this small sampling, gas chromatography has potential value across a range of fields and understanding how to apply and tailor analysis to specific applications will become more important in the future. Plus, unlike usual laboratory experiments, it was encouraged to taste these samples.

So today, join the revelers world-wide, celebrating Burns Night on the weekend following his birthday, and raise a dram of furfural/hexanoic acid/1-butanol to one of the world's greatest poets!

May 9, 2023 - Setting Acceptance Limits for Cleaning Validation of Medical Devices

Sheraton Denver Downtown, Denver, CO, USA. For general information about the workshop, please visit the event website.

ABOUT THE EVENT

Sponsored by ASTM Committee F04 on Medical and Surgical Materials and Devices, the workshop will be held in conjunction with the May standards development meetings of the committee.

This workshop will identify current best practices in setting acceptance limits in cleaning of medical devices, gaps in standardization of this practice, and areas where new standards would be useful. Considerations include crossover with ISO 10993 standards and potential updates to these requirements.

Workshop Topics

Topics include, but are not limited to:

• Case studies of cleaning with issues associated with acceptance limits
• Current standards on cleaning of medical devices
• Types of residues and considerations
  • Include manufacturing residues, particles, environmental agents, cleaning agents
  • Exogenous factors
  • Knowing what your manufacturing materials are composed of
• Methods for establishing acceptance limits
  • Historical clinical history
  • Toxicological risk assessment
  • Cytotoxicity
  • Patient risk assessment
• Approaches for using acceptance limits in cleaning validation
  • How cleaning affects sterilization
  • How cleaning affects biocompatibility
  • Consistency of cleaning process
  • Impact of cleaning on device functionality or user experience
  • Risk assessment in using acceptance limits
• When to modify acceptance limits
• Approaches to limit establishment when there is a change in manufacturing process
• What are the gaps in acceptance limits guidance?
• The pharmaceutical manufacturer position on acceptance limits
• Regulatory perspective on setting limits and rationale
• Development of proposal(s) for development of new ASTM standards related to acceptance limits for medical devices

WORKSHOP CALL FOR PRESENTATIONS

Abstract Submission

Please submit your 300-word abstract pertaining to the topics above to Workshop Co-Chairs Stephen Spiegelberg at stephen.spiegelberg@campoly.com and Ralph Basile at rbasile@healthmark.com by close of business January 20, 2023.