ISO 10993

How the New FDA Biocompatibility Testing Guidance Could Affect You

Thor Rollins is a Biocompatibility Specialist and Vivo Section Leader at Nelson Laboratories, Inc.

Thor Rollins ǀ Biocompatibility Specialist and Vivo Section Leader, Nelson Laboratories, Inc.

By Thor Rollins, Biocompatibility Specialist and Vivo Section Leader, Nelson Laboratories, Inc.

The following are excerpts from Thor Rollins’ article, How the New FDA Biocompatibility Testing Guidance Could Affect You, originally published in the May 2014 edition of MDDI Magazine.

In April 2013, FDA released draft guidance for industry and FDA administration staff titled “Use of International Standard ISO 10993, ‘Biological Evaluation of Medical Devices Part 1: Evaluation and Testing.’” Meant to replace FDA’s 1995 G95 document, the new draft guidance document is the most expansive presentation of testing standards affecting the medical device industry in more than 18 years.

In the past, performing medical device testing was like checking off boxes. Neither the device type, type and duration of contact, nor materials mattered. While G95 was used as a kind of checklist, the new guidance teaches testing professionals how to change materials or how to view testing in a more scientific way. It puts more emphasis on scientific analysis, thus compelling professionals to have more knowledge and background about the tests they perform. In addition, it contains good ideas on how to justify biocompatibility testing—specifically animal testing—and presents ways for limiting the use of such tests for certain devices.

While many of the ideas contained in the new guidance document have appeared in FDA response letters over the past two years and more, it also incorporates changes that are new to the medical device industry.


  • Test for All Types of Exposures: The first such change is that devices subjected to multiple types of exposures should be tested for all of them.
  • Conduct Extract Tests on All Components Separately: Another change in the new draft guidance document stipulates that if a device includes components that contact the body for different lengths of time… extract tests should be conducted on the components separately.
  • Use the Mouse Lymphoma Test for Genotoxicity: The new guidance document has settled on the mouse lymphoma test because it detects the broadest set of genotoxic mechanisms associated with carcinogenic activity.
  • Devise a Meaningful Test Outline: The new draft document puts greater emphasis than G95 did on the importance of knowing the scientific rationale behind the tests that are performed and devising a meaningful test outline for the device.
  • A Reference for Manufacturers: By codifying these standards in a single document, FDA has enabled medical device manufacturers and testing facilities to reference them in order to perform such tasks as setting up a test design or evaluating the impact of a failure.

For a more detailed analysis of the new draft guidance and how it may affect you, read the extended version of Mr. Rollins’ MDDI Magazine article on

ISO Meeting and Biocompatibility Standards Update, Mishima, Japan

by Thor Rollins, Biocompatibility Expert, Nelson LaboratoriesGC

I recently attended ISO (International Organization of Standardization) meetings in Mishima, Japan to participate in updating various biocompatibility testing standards. These updates are intended to reflect the best care and safety possible, regarding biocompatibility, for any given device. The updates discussed at this series of ISO meetings included the following:

  • Compound Limits: Safety limits need to be determined for each compound that can come off of a medical device during use. Currently, Ethylene Oxide (EO) gas is the only compound listed in an ISO standard that has a residual limit. However, the plasticizer diethylhexyl phthalate (DEHP), a plastic compound used in medical devices such as tubing, will likely have a limit set in the future.
  • Cytotoxicity Test: A test wherein a device, or portion of a device, is applied to living cells to see how the cells react to the materials used in the manufacture of the device. This is considered the most sensitive biocompatibility test and is a great screening tool for medical devices. The current cytotoxicity tests are qualitative; however the standard is now emphasizing the use of a quantitative version of the cytotoxicity test.   The early results from these quantitative methods have shown an increased sensitivity over the qualitative methods. A series of round robin tests are being planned to verify that the quantitative test method is consistently more sensitive.  These tests will then be followed by a discussion of clinical relevance of making the test more sensitive.
  • Different Population Limits of Chemicals: A person’s healthy limits for chemical exposure from using a medical device can vary depending on body size. For this reason, new standards for these limits are being discussed to introduce new limits according to the physical characteristics of the target population of the intended recipient. Currently, the industry standard is set for an average person weighing 70 kilograms (154 pounds), much higher than the weight of a child or infant. The new standard will consider the weights of intended populations, such as small children and infants.
  • Gas Path Devices: When using delivery systems that are intended to supply gases needed for medical purposes, compounds from those devices can come off and enter the human body. For this reason, it is necessary to standardize the effects of these compounds, in addition to the amount of compounds that will be allowed to be released during use.

Standards are reached through global consensus and serve to make the industry more efficient and effective, in addition to providing additional safety. As these standards are implemented, Nelson Laboratories will ensure the standards are met with the same quality as before.

What You’ll Learn at the MD&M West Nelson Laboratories Classroom on Materials Selection and ISO 10993 Biocompatibility Update

Thor Rollins, Biocompatibility Expert and Consultation MangerCytotoxicity-testing


Thor Rollins will present the latest information on standards affecting materials selection for medical device manufacturers at the 2014 MD&M West Conference. Thor is a Biocompatibility Expert and Consulting Manager at Nelson Laboratories in Salt Lake City, Utah. His presentation will include:

  • An overview of changes to last year’s FDA draft document, including rationale for the changes and how the draft may affect medical device manufacturers
  • Strategies and considerations for selecting materials for devices before development or early in the development cycle
  • What medical device manufacturers can do to proactively ensure materials are safe before the design stage
  • A summary of qualification processes required to ensure the safety of materials

Take Away:

  • Attendees will learn how to make smarter choices while selecting materials for medical devices, allowing them to save time and money later in the validation process
  • Attendees will gain a clearer understanding of the FDA’s intentions regarding implementation of ISO 10993, helping them be prepared before the FDA draft becomes an official guidance document


Thor will present for approximately one hour at the Nelson Laboratories classroom in 208AB on February 12, 2014 at 10:00 AM.

Register at

Nelson Laboratories website:

Nelson Laboratories to Offer Free Biocompatibility Consultations During BIOMEDevice San Jose

SALT LAKE CITY – Nov. 15, 2013 – Nelson Laboratories ( will offer free biocompatibility BIOMEDevice-SanJoseconsultations in its booth (#321) during BIOMEDevice in San Jose, CA Dec. 4-5, 2013 with expert Thor Rollins, biocompatibility specialist. Those interested in a consultation should register at

Rollins will also present, “Selection, Testing and Validation of Medical Devices According to ISO 10993,” from 10:00 am to 12:00 pm Dec. 5. The presentation is free, but participants should register at

“During the presentation, we will discuss materials that can have an impact on test results, which specific tests to use, and how to confirm test results,” said Rollins. “For those who want to dig a little deeper, we will also be conducting free biocompatibility consultations.”

During the consultations, participants can go over any biocompatibility topic they wish with Rollins. Some suggested topics may include:

  • Setting up a biocompatibility test plan
  • What happens if you fail a biocompatibility test
  • Materials characterization testing
  • ISO updates/changes
  • Materials justifications

Rollins’ presentation will cover:

ISO 10933 Test Requirements and how Materials Could Impact Biocompatibility Testing:

  • An overview of the most common biocompatibility tests and what materials could impact the results
  • How FDA and other regulatory agencies will interpret your results or test selection
  • How the new FA Draft Guidance might impact your future testing
  • How to categorize you device according to ISO 10993

Materials Characterization for Medical Devices per ISO 10993-17,18:

  • The correct way to extract your device to look for extractables and leachables
  • What tests to run to identify and quantify the compounds
  • How to determine the potential toxicological impact of the compounds

What To Do If You Fail A Compatibility Test:

  • How to confirm the result
  • How to trouble shoot and ways to improve you device
  • How to justify a failure

About Nelson Laboratories: Nelson Laboratories is a leading provider of full, life-cycle microbiology testing services. We are known for exceptional quality, but we look beyond the testing process and partner with you to achieve your long-term business goals. It’s what we call The Science of Success™. Learn how we can help move your products to market quickly and safely. Visit

Author: Thor Rollins |

Europe Working to Update Facemask Standard to Align with United States

By Todd Hillam, Protective Barriers Section Leader MBA, SM(NRCM)Bacterial-Filtration-Efficiency-test

There is an initiative afloat within the CEN Committee, the European Standards committee, to align the Bacterial Filtration Efficiency (BFE) test for medical facemasks with its counterpart in the U.S. The move will make it easier for facemask manufacturers to comply with the BFE test method requirements for both the EN 14683 standard in Europe and the ASTM F2101 standard in the U.S.

Right now, the BFE method differs in Europe and US by the pre-conditioning requirements.  Manufacturers have to test a set of masks for each standard increasing time and cost. The goal is to update the standard and align the pre-conditioning parameters so manufacturers will only have to test their facemasks once to meet each of the standard method requirements.

The benefit to manufacturers of the standard change is that they can conduct one BFE test that will be the same in each standard. It will help cut down on the number of submissions, save time, save on test costs and ultimately save in what manufacturers will need to charge for their products.

The committee decided to add a bioburden or microbial cleanliness test to the European standard as well as emphasize the requirement for Biocompatibility (ISO10993). These additions will help in controlling the manufacturing process and ensure the products are safe for use.

There are two other tests referenced in the EN 14683, Differential Pressure and Splash Resistance.  Differential Pressure will still not be aligned as it requires pre-conditioning in the EN standard but the US test uses an old military standard that does not require pre-conditioning.  Efforts are still being made to align the two methods.  Splash Resistance is being updated in the EN standard to reference ISO 22609 rather than ASTM F1862 (method used in US).  The two methods are the same so there should not be any concerns with this change.

The change to EN 14683 is in the ballot stage among the CEN Committee until a rejection of the changes or a final acceptance is made. Nelson Laboratories is currently equipped to provide testing services for both standards.

Editors note: Nelson Laboratories’ own Todd Hillam, who sits as a member on the U.S. ASTM committee, was invited to attend and make a presentation to the CEN Committee to help as an independent resource with the revisions.

2013 to Be a Big Year for Biocompatibility; Nelson Labs Participates in Potential Updates

SALT LAKE CITY, Sep. 16, 2013 – 2013 is shaping up to be a big year for biocompatibility and Nelson TRollinsLaboratories ( is in the thick of it with its involvement in the ISO 10993 Working Group, participation in round-robin testing of a potential in vitro replacement for Rabbit Irritation Testing and leading in the discussion regarding biocompatibility guidance on the horizon from FDA.

New FDA Draft Guidance

FDA placed into a draft guidance document its summary of ideas regarding biocompatibility and possible changes that could eventually replace FDA G-95 Blue Book Memorandum #G95-1 on biocompatibility.

“The draft document has been out since April and widely available,” said Thor Rollins, Biocompatibility Expert at Nelson Laboratories. “It has not been formally released, but there is a lot of buzz about the document. Many people are having a difficult time interpreting what is different, what has changed and what kind of impact it will have moving forward. Though only a draft, it does give insight on what FDA is thinking.”

The document is in three categories:

  • Summary of Ideas – a summary of ideas FDA has expressed for a few years.
  • Justification Ideas – FDA spells out general ideas of how to justify biocompatibility choices. FDA has never done that before.
  • Possible Impacts – shows possible impacts never before seen regarding biocompatibility.

(Read More)

ISO 10993 Working Group

Nelson Laboratories recently participated in the ISO 10993 Working Group’s Italy Sessions where three new updates were released.

Sensitization and Irritation – The European Center for the Validation of Alternative Methods (ECVAM) performed a validation for an in vitro irritation test for cosmetics to replace the rabbit irritation test. Nelson Laboratories is participating in the study to see if the validation will apply to medical devices in a three-phase process. A similar process will take place after ECVAM completes a similar validation for sensitization.

Systemic Toxicity – A new test will look at chemicals that are systemic, which is more concerning to toxicologists than localized toxicity. The goal is to find ways to become more efficient when looking at polar and non-polar extracts with toxicity studies.

Threshold of Toxicological Concern (TTC) – The working group is working to write a document that uses the concepts of TTC with medical devices in which you look at the chemicals coming off of a device and analyze them using safety information. This will be a key focus of the ISO 10993 working group leading up to the next meeting in Japan.

(Read More)

Replacement of Rabbit Irritation Test

Nelson Laboratories is currently participating in round-robin test validations involving several different labs to demonstrate that medical device extracts can illicit the same predictive response with the irritation tests as those conducted by ECVAM. If the tests are successful, the in vitro tests can potentially become more efficient, user fewer or no animals, and save costs and time. FDA currently does not accept the test for medical devices saying there is no proof that extractions can elicit a response. FDA approval will depend on the round robin testing.

As an active participant in each of these biocompatibility initiatives, Nelson Laboratories is uniquely qualified to guide medical device manufacturers on how these potential changes will affect their business and manufacturing processes. The Company’s scientists are available to answer questions regarding all aspects of biocompatibility. Read the Nelson Labs blog for more in-depth information on these topics. (Read More)

For additional in-depth information regarding these topics, Nelson Laboratories recently conducted a webinar entitled, “How the New FDA Guidance on ISO 10993 Could Possibly Affect You.”

About Nelson Laboratories: Nelson Laboratories is a leading provider of full, life-cycle microbiology testing services. We are known for exceptional quality, but we look beyond the testing process and collaborate with you to achieve your long-term business goals. It’s what we call The Science of Success™. It’s transparency in the testing process. It’s approachable experts that guide you through ever-changing compliance requirements. It’s helping you mitigate risk, be first to market, and succeed with your customers. Learn more at

Author: Thor Rollins |