Medical Device

FTIR in Assessment of Medical Devices

By: Adam B. Brigham, B.S.; Matthew R Jorgensen, PhD

Fourier transform infrared (FTIR) analysis is a popular analytical tool for material screening. The technique works because each different type of molecular bond in a molecule vibrates differently, and there is often a set of molecular vibrations that involve the entire molecule that form a characteristic “fingerprint.” When measuring a molecular substance, it is possible to identify an organic substance by comparing its FTIR spectrum to a library. In cases where a substance is a mixture of molecular components, FTIR would not be the best option because a separation technique (e.g. chromatography) would need to take place before identification could occur. However, there are many cases for which FTIR analysis is a fast and inexpensive option.

FTIR can be a useful first step as an aid in the identification of an unknown residue. Even if an exact identification is not possible (e.g. in the case of mixed residue), FTIR can often help identify the class of compound which can assist in unknown investigations or process monitoring. For example, if high residual manufacturing material was found on a device, FTIR could be used as an investigational tool to help identify the source. If FTIR was unable to find a conclusive library comparison match, additional testing would need to take place.

FTIR shines when comparing two or more materials in-hand. For example, when particulates are found on a device, it may be necessary to attempt particle identification so that the source can be found and eliminated. Other analytical chemistry techniques would fail at this task, because the amount of particulate material is too small to analyze. FTIR can be conducted through a microscope so that the “fingerprint” of a single particle can be collected. This spectrum can be compared against potential contaminants (e.g. paper, fibers from clothing, or materials unique to the device manufacture), or a library of materials which can greatly narrow the possibilities.

There are also cases where the question being asked is, “does a certain process change my material?” FTIR is a great resource for polymer characterization. Depending on the nature of the material and process, it may be possible to pinpoint what the change is. For example, oxidation of a polymer is clearly indicated by the introduction of carbon-carbon double bonds. If the details of the change are not derivable, it can at least detect if a change has occurred. Perhaps a manufacturer considers changing the radiation dose for their material; they can measure the original device and a device irradiated at the new level comparatively to see if anything is different.

Any FTIR study relevant to medical devices should be carefully thought through and designed with expertise. Simply ordering of a single test without a specific objective in mind will be marginally useful. With smart design – powerful conclusions can be made.

Nelson Laboratories’ Experts Receive SOT Award

During the annual Society of Toxicology (SOT) meeting in Baltimore, Maryland, Michelle Lee and Audrey Turley from Nelson Laboratories were two of eleven authors awarded Best Overall Abstract for “Round Robin Study to Evaluate the Reconstructed Human Epidermis (RHE) Model as In Vitro Skin Irritation Test for Detection of Irritant Activity in Medical Device Extracts”. This abstract resulted in a poster presentation on the results of a worldwide collaboration to demonstrate the application of an in vitro skin irritation method for medical devices.

SOT_AwardThe acceptance of this method could significantly reduce the animal testing needed when determining the biocompatibility of medical devices. The initiative to reduce animal testing has primarily been led by Europe, but US regulatory bodies are adopting the initiative as well.

The irritation test is based on exposing RHE to device or material extracts, then performing a viability assay (using an MTT assay) where limits have been established to determine irritation potential based on an adopted method for chemicals from OECD 439: In Vitro Irritation: Reconstructed Human Epidermis Test Method.

Nelson Laboratories has been involved with this project long before it came to SOT, through our membership on the ISO working group for irritation. We have worked in conjunction with medical device manufacturers for this round robin. Look for a review of the official publication for this groundbreaking work in the near future.

Cleanroom Renovation Complete

At Nelson Laboratories, our values hinge on quality, service, and expertise. Our quality systems and world-class facilities are part of what elevates us in the MedTech industry.

We recently completed a two-year renovation to our state-of-the-art ISO Class 5 cleanroom. This space is where we perform important product sterility testing.

“I commend our product sterility team and laboratory management for the great coordination and management of this project,” said Jeff Hone, Vice President of Quality at Nelson Laboratories. “This puts us in a state of compliance with our cleanroom that will serve us for years to come.”

During the cleanroom renovations:

  • The isolator testing units were moved to a new, dedicated testing space to allow for more room related to product sterility testing – (additional space for sample processing and storage)
  • The floors were resurfaced with a solvent resistant surface to improve the ability to clean
  • The cleanroom walls were replaced with a high end cleanroom surface which is chemical resistant, easily sanitized and highly durable
  • Two new laminar flow hoods were installed
  • Low particulate construction materials were used to improve particulate interface

If you have any questions, please contact the Sterility Department Section Leader, Jonathan Swenson, at jswenson@nelsonlabs.com.

Reprocessing Single-Use Devices

By Emily Mitzel & Paul Littley

Some devices that are marketed and validated for single use are now being used multiple times in clinical settings. To save money and to comply with green initiatives, hospitals are moving towards using third-party reprocessed single-use devices (SUDs). However, reusing devices intended for single use can be dangerous without the correct validations and instructions for reprocessing in place.

single-use-blog-post-1Post-market validations need to occur to reuse devices intended for single use. Since there are no reprocessing instructions for use (IFU) for SUDs, cleaning and sterilization processes must be developed and validated to ensure patient safety.

FDA and other regulatory bodies have some guidance documents and are creating more to make sure SUDs can be appropriately cleaned, disinfected, sterilized, and tested for functionality. A test plan, justification, and acceptance criteria should be written to conform to regulatory trends.

FDA is hosting a public workshop, Refurbishing, Reconditioning, Rebuilding, Remarketing, Remanufacturing, and Servicing of Medical Devices Performed by Third-Party Entities and Original Equipment Manufacturers, in October and has started a draft document to help regulate and provide guidance to this industry.

There are many items that need to be addressed to successfully reprocess SUDs.  The experts at Nelson Laboratories provide the following services to help third-party reprocessors with their process validations:

  • Cleaning process and parameter development including validation
  • Disinfection process and parameter development including validation
  • Sterilization cycle development including validation
  • Packaging validations for device sterile barrier systems in preparation for sterilization, transportation, and shelf life
  • Family grouping of devices for validation
  • Environmental Monitoring (EM) program involving review of current program, gap analysis, and development of EM sampling plans
  • Assessment of current water systems design and status, including: determination of the appropriate type of water, gap analysis, and testing to ensure compliance to the water grade specified
  • Training program development or review; which includes reprocessing techniques, EM sampling, etc.
  • Regulatory compliance consultation; which includes regulatory responses, audit support, and on-site process inspection and evaluation with written assessment as appropriate

single-use-blog-post-2Third-party reprocessing offers healthcare providers a way to maintain the highest quality patient care, while also achieving significant cost-savings and reducing medical waste.  This is only possible if all regulatory requirements are fulfilled and the devices are reprocessed for safely for subsequent patient use.  This savings has been reported to be millions of dollars in supply costs and millions of pounds of waste diverted from landfills.

US FDA recommends using the guidance from Medical Device User Fee and Modernization Act of 2002, Enforcement Priorities for Single-Use Devices Reprocessed by Third Parties and Hospitals, and Labeling Recommendations for Single-Use Devices Reprocessed by Third Parties and Hospitals; Final Guidance for Industry and FDA. Medical Device and Diagnostic Industry published Reprocessing Single-Use Devices: Why Does the Debate Continue?  The Association of Medical Device Reprocessors (AMDR) website has a lot of information such as Regulatory Position Statements and Letters and International Regulations.  Health Canada published an update in 2015 on Reprocessing of Single-Use Medical Devices which includes the policies and practices appropriate for each Canadian jurisdiction.

Validated cleaning, disinfection, and sterilization processes combined with validated functionality testing can ensure patient safety when reusing single-use medical devices.

Please contact Nelson Laboratories Experts for your consulting needs:

Emily Mitzel: emitzel@nelsonlabs.com

Paul Littley: plittley@nelsonlabs.com

New US FDA Guidance on the Use of International Standard ISO 10993-1: Top 10 Changes

As anticipated, the United States Food and Drug Administration (US FDA) issued a new guidance document on the use of ISO 10993-1 on June 16, 2016. In one statement the FDA summarizes how they want to see biocompatibility for medical devices supported: “For FDA submissions, biocompatibility information for the device in its final finished form, either developed through the risk management process or from biocompatibility testing (using both in vitro and in vivo models), and/or adequate chemical characterization in conjunction with supplementary biocompatibility information that adequately address the biocompatibility risks of the device should be provided.”

The guidance document doubled in length over the previous draft – there is a lot of new information. Here are our top 10 highlights:

  1. Device Examples: This version includes more communication and examples to support device companies in their submissions. Evidence is in the 5 additional attachments and the 30 page increase over the previous draft.
  2. Practitioner Contact: Assessing risk based on practitioner contact with devices now falls under ISO 10993-1 which expands the scope beyond patient safety.
  3. Recognized Standards: Important to note US FDA references other standards that are relevant to biocompatibility testing (ASTM, OECD, ICH and USP).
  4. Risk Management Guidance: Section III Risk Management for Biocompatibility Evaluations is a new lengthy 10 page section with great examples and discussion of how to approach and assess risk.
  5. Decision Trees: As described in the document assess risk BEFORE testing begins. This should be laid out in a Biological Evaluation Plan.
  6. FDA ISO Biocompatibility Matrix Updates: FDA Modified matrix is “…not a checklist…” Added separate column for Material-Mediated Pyrogenicity.
  7. Cytotoxicity Tests: Extraction time for cytotoxicity testing is identified as 24-72 hrs extraction. This differs from ISO 10993 and possibly implies that all permanent implants should be extracted for longer periods (72 hours).
  8. Hemolysis Tests: Only indirect hemolysis testing is now allowed for devices with indirect blood contact. Complement Activation no longer requires analysis of C3a. Serum is now preferred over plasma.
  9. Genotoxicity Tests: Genotoxicity testing may be waived if chemical characterization testing and literature research indicate that a genotoxic risk does not exist. However genotoxicity testing and research cannot be used to mitigate carcinogenic risk.
  10. Pyrogenicity Tests: Pyrogenicity testing is expanded to include the Bacterial Endotoxin Test (BET) for sterile devices having direct/indirect contact with the cardiovascular system, lymphatic system or Cerebral Spinal Fluid (CSF) regardless of contact duration.

Look for our webinar early August where we will go over these highlights and so much more. The FDA is presenting a webinar on the new guidance document on July 21st. If you have any questions or concerns in the meantime, contact our Toxicology and Biocompatibility experts in the Nelson Laboratories technical consulting group.

Audrey Turley – Research Scientist

Thor Rollins – Biocompatibility Expert

Dr. Sarah Campbell – Toxicologist

Trevor Fish – Toxicologist

Dr. Matthew Jorgensen – Material Science

3D Printed Devices and Biocompatibility: Post-Printing and Finishing

 

Matthew R. Jorgensen, PhD; Alexa Tatarian, BS

In the previous two posts, the biocompatibility of 3D printed devices was discussed with consideration for the possible compounds added to the raw materials for workability and the polymer precursors and byproducts associated with photopolymerized structures. In both of these cases, the discussion focused on the materials designed to be part of the final structure. Here, the introduction of compounds from the sacrificial support material, post-printing rinsing, and finishing processes are discussed; all of which are secondary to the device material itself.

3D printing offers facile creation of complicated devices by depositing the structure additively along with a selectively removable support material. The support material allows the printing of overhanging parts by providing a structural platform for the device material, and can act as a thin layer between parts that are printed very close to each other but should be prevented from fusing (think, for example, of printing a device with movable gears). Without sacrificial support materials, 3D printed designs would be severely limited. Because the support material is not intended to be part of the finished device, it may be overlooked as a possible source of biocompatibility issues.

After printing, the sacrificial support material (which is generally dissolvable in a water based cleaning solution) must be removed. The compatibility of the support material depends on the printing technology used. Methods that deposit thin lines of thermoplastic use a special water-soluble polymer or break-away material, while photopolymerization methods may use a loosely polymerized gel or unexposed photopolymer as support materials. Laser sintering methods (often used to produce metal and metal oxide parts) use un-sintered precursor powder.

Each support material and removal method raises potential concerns from a biocompatibility perspective.

3D 3

Following removal of support materials, 3D printed devices may undergo subsequent finishing processes. Extruded thermoplastics may be smoothed through exposure to heated solvent vapors such as acetone or methylene chloride. The combination of heat and natural affinity of the solvent for the material creates ideal conditions for adsorption into the material surface. Metal parts may undergo passivation processes that introduce surface contaminants. Desorption of volatiles from 3D printed material will be discussed next week.