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Thirsty the Hydrogel
Was a sodium polyacrylate soul
With a Bakelite pipe and a resin nose
And two eyes made by injection mold

Oh, Thirsty the Hydrogel
Is a feat of science, so they say
He was made of fake snow
And the lab techs know
How he wicked moisture away

There must have been some water in
That plastic hat they found
For when they placed it on his head
He began to swell around

Oh, Thirsty the Hydrogel
Was absorbent as he could be
He could hydrate
to 300 times his weight
Not the same as you and me

Oh, Thirsty the Hydrogel
Knew the temp was warm that day
But he said, "Let's play and perform TGA
Because I won’t melt away"

Down to the laboratory
With a pipette in his hand
Running here and there
Volumizing scientists’ hair
Saying, "Deform me if you can"

They chased him through the lab benches
Right past a Research Scientist II
And Thirsty only stopped a moment
When she yelled, “You’re not wearing shoes!!!!"

Hmm, Thirsty the Hydrogel
Had to apply his linking agent spray
No need to wave goodbye, he said, "Don't you cry
Because crosslinks save the day!"

Slurpity, slurp, slurp, slurpity, slurp slurp
Look at Thirsty grow!
Slurpity, slurp slurp, slurpity, slurp slurp
Over streams of aqueous flow!

CPG Holiday Hours

In observance of the holidays, Cambridge Polymer Group will be closed on Friday, December 22nd, and Monday, December 25th. We will be open Tuesday, December 26th, to Thursday, December 28th, closing again on Friday, December 29th, and Monday, January 1st. We will return to regular business hours on Tuesday, January 2nd.

Figure 1: Compilation of bullet hole damage found on planes that returned from battle.

In analysis of data, bias can lead to an incorrect interpretation of the data if the analyst has a firmly-held preconceived notion of the study outcome, or if a complete dataset is not considered. The analyst may not be aware that they are biasing their data interpretation. A careful analyst will always question their study interpretations to make sure that bias has not crept in.

Mathematician's Insight Led to Critical Breakthrough in World War II

An example of bias can be found in World War II. The Navy wanted to reduce airplane loss during battles. They thought more armor reinforcement would help protect the planes, but they needed to be strategic in where to place the armor; heavier planes used more fuel and were less maneuverable. They collected data on the accumulated bullet holes on planes returning from battle in Europe, and compiled it into an image like that shown in Figure 1. They noted that the bullet damage was largely segregated to the wings and fuselage, and there was little damage to the engines. Based on this analysis, they initially concluded that more armor was needed on the wings and fuselage.

A statistician in their group, Abraham Wald, looked at the data and had a different interpretation after considering the larger picture. He realized that a dataset was missing from the analysis, namely the planes that did not return from battle. All the planes that led to the data set in Figure 1 were able to return to base and, hence, did not have critical damage.

Wald initially speculated that bullets holes should be randomly distributed over the plane and that the dataset in Figure 1 was biased by considering only the planes without critical damage. He further speculated that planes that took hits to the engines were unable to return to base, suffering critical damage and, hence, were not part of the dataset. In consideration of the entire dataset, the conclusion would be to armor the engines, and that the wings and fuselage could withstand damage without crashing. Wald therefore looked for where there were no bullets to arrive at his conclusion.

Overcoming Bias in Medical Device Materials Analysis

Cambridge Polymer Group considers this approach when conducting analysis projects for clients. For instance, in extraction studies for ISO 10993-18, if we do not see potentially toxic compounds in an extract using one detector, we use another detector on the same extract to see if compounds are identified with a different detection mode. This approach is particularly necessary when we are looking at the bill of materials for a medical device to identify what detector will reliably pick up potential extractable materials. Just because one detector does not pick up a compound does not mean the compound is not there.

Cambridge Polymer Group is helping to organize a workshop on Best Practices for Precision and Bias for Medical Device Standardization, to be held in May of 2024 in Philadelphia. This workshop will discuss how to conduct interlaboratory studies on test methods to generate statistical information relevant for a precision and bias (P&B) statement in an ASTM test method, how to use P&B information, and when a P&B study is not appropriate.

A call for abstract submission will be going out later this year. Please contact Cambridge Polymer Group if you would like to present or attend the workshop.

Although this title manages to capture three yawn-inducing groups of words[1] (“non-volatile residue,” “standardization”, and “ASTM”), when these groups are combined, they represent an important subject for manufacturers of medical devices. Non-volatile residues (NVR) are those residues that can be removed from a medical device that are not intended to be part of the device, and are of sufficiently low volatility that they do not evaporate upon removal of extraction solvent. NVRs are often used to assess how clean a device is, or how effective a manufacturing process is.

The American Society for Testing and Materials (ASTM), the United States Pharmacopeia (USP), and the International Standards Organization (ISO) employs the concept NVR in several of their standards. For example, in extraction and leaching studies of medical devices used for chemical risk assessment per ISO 10993-18 and USP, NVR measurements of components that can be extracted from finished medical devices are used to established both the total mass of extractable residue as well as an indication of whether exhaustive extraction conditions have been achieved.

NVR Standards for Medical Devices

Scientists at Cambridge Polymer Group are involved in drafting several new standards involving NVR assessment. In ASTM committee F42.07.03 for additive manufacturing of medical devices, a new standard is being developed to quantitatively measure residual powder bed feedstock on additive-manufactured medical devices, with one required test using NVR measurements. This draft standard is currently titled Standard Test Method for Additive Manufacturing for Medical – Powder Bed Fusion – Assessment of Residual Powder (WK82776).

Another standard that involves NVR measurements is ASTM F2459 Standard Test Method for Extracting Residue from Metallic Medical Components and Quantifying via Gravimetric Analysis, which is primarily used as a measurement of how clean medical devices are. This standard, which originated at Cambridge Polymer Group, is currently being modified to include plastic and ceramic medical devices.

At Cambridge Polymer Group, we are regularly involved with measuring NVR in medical devices to help ensure safety and compliance to standards. Contact us to have us help you with your NVR measurements.

CPG Employee Spotlight: Dr. Rebecca Bader

Dr. Rebecca Bader is Cambridge Polymer Group's Associate Director of Chromatography and our biocompatibility specialist. She has a PhD in Materials Science from Oregon State, a master’s in chemistry from Princeton, and has taught biomedical engineering at Syracuse University. Becky worked for CPG for four years until 2019 when she moved to the West Coast. We are thrilled that she has returned, both to the East Coast and to CPG.

How did your time away from Cambridge Polymer Group help you in your current role?

“I worked with a pharma company, doing contract research for formulations and drug delivery. I picked up some GMP skills. I decided though that I wanted to work in medical device because I really missed contract research in material science. I very much missed materials, so I took a series of NAMSA classes on 10993-18 and biocompatibility to get into the industry. I leveraged that certificate along with my previous CPG experience to apply for biocompatibility expert roles, which focused on my material science expertise combined with my knowledge of the ISO standard.

I was hired by a medical device company as a biocompatibility engineer in their Regulatory Affairs department. I was able to pick up on FDA and EU regulatory expectations, beyond just biocompatibility.

Over the past two years, I also completed some women’s leadership courses from Cornell University."

Now that you’re back on our team, how do CPG clients benefit from your experience?

“I can now provide more regulatory input as well as biological risk assessments that are tailored to the appropriate market.”

Do you have any advice for women trying to advance in science?

“It’s OK to stand your ground and to ask for what you think you deserve. Those are both things that women struggle with inherently, a little bit. Women tend to be less confrontational. I also think it’s OK to be emotional sometimes.”

What is your favorite part of your job?

“I get to work with brilliant people who care about science and are ethical and above board. Also, I love bringing in new business related to medical device and biocomp.”

What are your favorite activities outside of the office?

"Triathlon. My gift to being an athlete is endurance. I can hold the same effort level indefinitely. I used to be a competitive marathon runner but I’ve switched to only racing Ironman where the marathons are a little slower.

I’ve been to the world championships four times now, and I’m not satisfied with how I’ve done, so I keep going back to race. This past year I had heat stroke and Covid, it was the slowest race I’ve ever done.

Running is my favorite thing in the whole world; it’s my stress release. I love training with my dogs and my person, Adam. I have springer spaniels because they’re the most hyper dogs, and they suit my personality. They run with me, they swim, they’re very Becky-like. Adam shares my love for exercise and my passion for material science.”

Becky is racing Ironman in Lake Placid this week, but she'll be back next week, ready to apply her winning combination of expertise and endurance to your material science challenges. Feel free to reach out about your ISO 10993 needs.

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.