NLI

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.

New Approaches to Assessing Biocompatibility for Medical Devices

Audrey Turley

The regulatory environment for biological safety evaluation of medical devices is changing rapidly. Biological safety evaluations following ISO 10993 have typically been addressed with biocompatibility  testing on animals; however, alternate options are now available using literature research and chemical characterization tests when appropriate to reduce animal testing. Considerable progress is being made in the development and standardization of new in vitro test methods; particularly for cytotoxicity, sensitization and irritation, the basic tests performed for any medical device regardless of the device’s application. These alternative in vitro methods provide multiple benefits, including: less sample amount, less time required to perform the test, and reduced animal use.

Click here to view Research Scientist Audrey Turley’s presentation from MD&M West 2016.

What will be learned:
• Learn how to use a risk assessment approach for process and material changes
• Understand how to use material and chemical characterization to reduce animal testing
• Update on development of alternative in vitro testing methods for irritation and sensitization

 

FDA Proposes Ban on Powdered Surgeon’s Gloves, Powdered Patient Examination Gloves, and Absorbable Powder for Lubricating a Surgeon’s Gloves

Sterilization-of-reusable-trayFDA is proposing to ban powdered surgeon’s gloves, powdered patient examination gloves, and absorbable powder for lubricating a surgeon’s gloves. The Agency determined that an unreasonable and substantial risk of illness or injury may occur from using these medical products and the risk cannot be corrected or eliminated by labeling or a change in labeling.

Electronic comments are encouraged for docket number FDA-2015-N-5017 RIN 0910-AH02 and can be submitted via this link.

The Federal Food, Drug, and Cosmetic Act (FD&C Act) of 1976 states that any device presenting an “unreasonable and substantial risk of illness or injury” that cannot be, or has not been, corrected or eliminated by labeling or a change in labeling must be banned. FDA has been considering banning the use of powder on gloves since 1997 when it issued the Medical Glove Powder Report. At that time, FDA decided that the benefits of using powder with surgical and patient gloves outweighed the risks. Since then, FDA has received many citizen petitions regarding the use of glove powder.

As a reaction to the 1998 petition to review its stance on the use of powdered gloves, FDA reconsidered a ban on powdered gloves in 1999. Three main factors kept the ban from taking effect: (1) A ban would not address exposure to natural latex allergens from medical gloves with high levels of natural latex proteins; (2) a ban of powdered gloves might compromise the availability of high quality medical gloves; and (3) a ban of powdered gloves might greatly increase annual costs by almost as much as $64 million over the alternative approach proposed by FDA in the “Draft Guidance for Industry and FDA Staff: Medical Glove Guidance Manual.”

FDA is yet to finalize the ban. The Agency possibly has not received all the information regarding the risks and benefits of powdered gloves, so Nelson Laboratories, Inc. is encouraging anyone who is interested in this topic to submit comments to FDA via the link above.

Nelson Labs Experts Invited to Present at Joint Conference

Thor Rollins, consulting manager, and Audrey Turley, research scientist, have been invited to speak at the joint conference of the Association of Analytical Communities Southern California Section (AOAC SCS) and Food and Drug Agency (FDA) 2016 Spring Conference. Rollins and Turley will be presenting the morning of Wednesday, April 27 at Chapman University, School of Pharmacy, Irvine. Click here for the full agenda.

DSC01871Rollins will be presenting on the application of chemical characteristics to medical devices. His presentation will cover how the industry is taking extractible and leachable applications and applying them to medical devices. The discussion will focus on what the challenges are, what benefits they have, where we are right now with the program and speculate about what these applications mean to the future of medical devices.

“I am excited for the opportunity to contribute to the discussion with colleagues and FDA experts about the future of the science behind biocompatibility and medical devices,” said Thor Rollins.

Turley will be presenting on in vitro alternatives to traditional animal testing. Specifically, she will be talking about in vitro irritation, sensitization and thrombogencity.

Visit the Nelson Labs website to view recent presentations by Rollins, How to Use Biocompatibility to Evaluate Changes in Medical Devices, and Turley, New Approaches to Assessing Biocompatibility for Medical Devices.

BIOMEDevice San Jose Focus On Biocompatibility

BIOMEDevice San Jose - Biocompatibility Training InvitationPlanning your BIOMEDevice conference schedule? Be sure to leave room for Nelson Laboratories, Inc. Nelson Labs will be offering a full schedule of biocompatibility focused lectures at BIOMEDevice San Jose, December 3 – 4, 2014, while also exhibiting in booth #321.

Bob Michaels’ recent Medical Product Manufacturing News (MPMN) Q&A interview with Nelson Laboratories’ biocompatibility expert, Thor Rollins, provides a sneak peek preview of the topics to be discussed in Rollins’ upcoming BIOMEDevice lectures. The following are excerpts from Mr. Michaels’ article, What Types of Biocompatibility Testing Do You Need To Perform? Visit qmed.com to read the complete interview.

MPMN: Please go into ISO 10993-1 and why cytotoxicity testing is used for screening medical device materials.

Rollins: Cytotoxicity testing is used for screening materials because it is sensitive. In the body, body systems help protect against cytotoxins, protect the cells to wash away any pH imbalances, or even deal with some of the concentration issues or pressures that the cells cannot handle by themselves. Thus, to determine the potential impact of cytotoxicity testing, we take the device and put it right on the cells and then bombard the cells with pH, particulates, and osmotic issues. Thus, during testing, cells are subjected to substances that may not exhibit toxicity in the patient or that could only have a toxic effect if they are present in the body in large quantities. …

MPMN: How should a medical device manufacturer decide which tests are most appropriate for a given device?

Rollins: This is the $1 million question for most of the tests that we perform. …
The amount of data required about a material and the depth of the investigation depends on the intended use of the device and the processes used to manufacture it, in addition to its function and how long it will have contact with the patient. Thus, if you have knowledge of the materials that were used to make the device and data about the potential leachable compounds, this information can be used together with a biological safety evaluation to help pool which types of testing are necessary. In other words, you take the history of the history, the processing methods used to create it, and some chemistry analysis and then evaluate all of these endpoints to help decide which testing should be performed to show that the device is safe. Thus, instead of using ISO 10993-1 as a series of checkboxes, you approach the safety assessment of the device scientifically based on several factors.

Each of Thor Rollins’ BIOMEDevice lectures is slated to focus on a different aspect of the swiftly evolving biocompatibility testing landscape, providing MedTech professionals the knowledge they need to navigate the challenges inherent in contemporary biocompatibility testing. Mark your calendar for Thor Rollins’ three Tech Theater presentations Wednesday December 3rd, and register for his Conference Presentation Thursday December 4th. To learn more visit www.nelsonlabs.com.

Half-Day BIOMEDevice Biocompatibility Lecture Series:
Wednesday December 3, 2014

  • 12:30 pm – 1:15 pm: Rethinking The Big Three: Cytotoxicity, Sensitization, & Irritation
  • 1:30 pm – 2:15 pm: The Power of Chemical Characterization to Assess Changes in Your Medical Device
  • 2:30 pm – 3:15 pm: How the New FDA Guidance on ISO 10993 Could Affect You

Biocompatibility Conference Training (BIOMEDevice registration required):
Thursday December 4, 2014

  • 2:45 pm -4:00 pm: Material Selection and Sampling Techniques for Biocompatibility ISO 10993

ISO 16775: The Medical Device Packaging Professional’s Latest “Must Have”

Medical Device Package Testing. Learn more at www.nelsonlabs.com.

Medical Device Package Testing. Learn more at www.nelsonlabs.com.

By: Jennifer Gygi, Nelson Laboratories, Inc. Packaging Department Scientist, SM (NRCM)

If you are involved in the packaging of medical devices, your primary standards reference has probably been the International Organization for Standardization (ISO) 11607 publication for packaging design and validation. However, this standard was lacking much of the detail and guidance many packaging engineers were seeking; therefore ISO recently published a new standard, ISO 16775 – Packaging For Terminally Sterilized Medical Devices – Guidance On The Application Of ISO 11607-1 And ISO 11607-2, a comprehensive guide to all things packaging.

The new standard references the fundamental concepts outlined in ISO 11607 but takes it to the next level, providing practitioners additional detail.  More specifically, ISO 16775 highlights what makes a sterile barrier system (SBS), what the SBS requirements are, design considerations, materials selection, labeling issues, and package assembly to name a few.

ISO 16775 also details common packaging configurations and applications, and walks users through the entire package testing process step by step. From creating the validation plan to installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ) on the sealing equipment, to testing final product/packaging for strength, integrity, and microbial barrier properties over time, ISO 16775 has you covered.

Where ISO 11607 speaks in generalities, ISO 16775 gives specifics. The meat of the document is found in the 19 appendices covering topics including but not limited to:

  • Guidance for health care facilities for creating SBS and performing validations
  • Selection of materials, design input, risk analysis tools, and sampling plans
  • Using contract packagers
  • Establishing processing parameters
  • Failure investigations, and design feasibility

ISO 16775’s appendix even includes example forms / checklists that can be used for IQ, OQ, and PQ  validations.

How ISO 16775 May Affect You

ISO 16775 is a “must have” for medical device packaging professionals.  It covers not only pre-formed SBS systems, but addresses many of the challenges unique to health care facilities, with extensive information on wraps and containers.

If you are experienced in medical device packaging, ISO 16775 will be a review of topics you are already familiar with, supplemented by new and valuable insights.  If you are a newcomer to packaging, this document is your new best friend.  ISO 16775 is a great reference to add to any library.