MedTech Industry News

Everything from GDP per capita, venture capital, M&A, interesting statistics and more. This may not be all of the news available about MedTech but it will be some of the most interesting and interpretive.

AAMI STERILIZATION STANDARDS MEETING UPDATE

By Emily Mitzel, MS

On March 20-23, 2017, I attended the Association for the Advancement of Medical Instrumentation (AAMI) semi-annual Sterilization Standards Committee Meeting. These Association meetings, and the standards discussed during them, have a major impact on medical device manufacturers, testing facilities, HCF managers, and FDA.  It is important for industry experts to participate in these meetings to ensure the standards and technical informational reports reflect current industry changes and trends, and to make sure the standards are written scientifically.

In addition to the satisfaction of positively impacting global health, participating on these committees allows me to stay up to date with the standards and understand what is trending in the industry. The clients I work with benefit because I can make sure they are meeting current and future regulatory requirements.

Highlights from the meetings include:

  • Working Group 93. TIR 30: 2011. This document needs to be updated to reflect current standards and published documents. A task committee, which included me, was established to determine the updates.
  • Working Group 40. ST79. This group finished reviewing all comments. It was noted that the document has been placed on AAMI public review but still needs to be placed on ANSI public review, and this could drive public review comments that will need to be discussed.
  • Working Group 13. ISO 15883 series. I provided an update from the February 6-8, 2017 interim meeting of ISO/TC 198/WG 13. Comments are still being resolved on ISO/DIS 15883-4, Washer-disinfectors – Part 4: Requirements and tests for washer -disinfectors employing chemical disinfection for thermolabile endoscopes, and that work will continue in April. The majority of this group’s time was spent on ISO 15883-5, Washer-disinfectors – Part 5: Performance requirements and test method criteria for demonstrating cleaning efficacy. Substantial changes and additions were made to the document during the February meetings that required discussion. ISO/CD 15883-5 is out for ballot and comment until April 2017. It was also reported that there will be a major revision to ISO 15883-1, Washer-disinfectors – Part 1: General requirements, terms and definitions and tests to begin soon.

In April, I will be attending the ISO meetings as a U.S. delegate. The standards that will be discussed at this meeting are ISO 17664, ISO 15883-1, ISO 15883-4, and ISO 15883-5.

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.

ISO Committee Member Announced

erinbakesErin Bakes has been accepted as a U.S. expert to the ISO Technical Committee 150: Implants for Surgery (WG7).  This placement allows participation in the annual ISO meetings to discuss movements surrounding the approach to cleanliness and safety of medical devices and the development of ISO 19227.  These meetings have recently been closed, and only those that are nominated and accepted by the co-chair of the respective working groups are allowed to attend and participate in the international annual meeting.

Erin Bakes has been with Nelson Laboratories for over ten years.  She has spent eight years as a study director in the chemistry department with a focus on cleaning validations for newly manufactured and single use devices.  She is now the chemistry department manager and continues to consult with clients on their device cleanliness validations.

U.S. ISO Certified Experts Announced

 

Thor Rollins, Michelle Lee, and Audrey Turley have been accepted as U.S. experts to four working groups in the Biological Evaluation ISO Technical Committee 194: WG5 (Cytotoxicity – Thor), WG8 (Sensitization and Irritation – Michelle), WG9 (Effects on blood – Michelle), and WG6 (Genotoxicity, Carcinogenicity, and Reproductive Toxicity – Audrey). This placement allows participation in the annual ISO meetings to discuss changes to the ISO 10993 and movements surrounding the approach to biocompatibility of medical devices. These meetings have recently been closed, and only those that are nominated and accepted by the co-chair of the respective working groups are allowed to attend and participate in the international annual meeting. Meet the experts:

Thor Rollins started his career at Nelson Laboratories as the study director over cytotoxicity testing. He is familiar with the test procedure and can speak to its application to medical devices providing a deep knowledge of all the complexities that can occur in cytotoxicity testing. Thor frequently works with clients who run into issues with cytotoxicity and need help mitigating patient risk.

Michelle Lee has been highly involved in several ISO round robins over the last few years including a Hemolysis, Complement, and currently an in vitro irritation round robin. Nelson Laboratories have been the top testing laboratory involved providing input on sample type, sample preparation, and protocol development for these projects. Michelle is also working to develop an in vitro sensitization assay using 3D human tissues.

Audrey Turley was one of the key personnel in bringing the in vitro chromosomal aberration assay in-house at Nelson Laboratories. Once the test was validated, she stepped in as the study director for the next six years. Currently, Audrey is working as a technical consultant to help clients perform risk assessments to address carcinogenicity risks.

Human Factor Considerations for Medical Device Manufacturers

By: Alpa Patel, B.S., RM (NRCM) and Alyessa D’Ewart, MPC

AlpaPatelConsideration of human factors when designing a medical device should be a high priority. It is important that concerns regarding human factors are considered during the development phase of new medical devices. For many years, this phase of the process has been overlooked and ignored; however, great efforts have been made so that user errors are eliminated or reduced as much as possible. The FDA has released a human factors guidance document for medical device manufacturers. This document provides steps and guidance manufacturers should take to ensure new devices do not have potential for dangerous outcomes due to human error.

Risk Management

The risk management process for each medical device should include the elimination or reduction of hazards due to user error. User-related hazards generally occur when a user cannot interpret the correct use of the device or instruction for use (IFU) correctly. Human factors engineering and usability engineering should be incorporated into the risk management in the early development stages of the process to help manufacturers identify anticipated and unanticipated user-related hazards. Undertaking the human factor tasks during the early stages can help develop measures to reduce the possibility of user-related errors, and would demonstrate how the design supports safe and effective use.

When conducting the risk management analysis, it is important to consider not only the device users but also the user environment, and the user interface. Device users can range from professional caregivers, to installation and maintenance professionals, to patients and their family members. Regardless of the intended user, the device should be able to be used without potentially life-threatening errors. The characteristics of each intended user population is important to consider in the design of the device to accommodate the varying limitations of each intended user population. The user environment should also be analyzed as lighting, noise levels, equipment, and people in the room can distract users during performance.

The major factor to consider during a risk management analysis is the user interface of the device. This includes all points of interaction between the intended user and the device itself. Elements such as the size and shape, software systems, components or accessories, and how the intended user manipulates the device should be deliberately chosen to reduce the amount and severity of user-related errors. It is also important that the information and manipulation of the device is laid out in a logical sequence for the intended user. Users will expect medical devices to function similarly to other devices they have used, and disrupting this flow may cause user-related errors.

Evaluation Methods

User tasks for each medical device should be identified and categorized based on the amount of potential harm that could result from user errors in each task. The tasks should be analyzed to determine the errors a user might make, the circumstances that may cause a user error, the potential harm from the error, and how the occurrence of the error might be reduced or eliminated. Critical tasks are those where serious harm could come from the task being done incorrectly or not at all. These tasks may change as the device design is modified, so it is important to continually reassess the critical tasks. It is also helpful to identify user-related issues in similar medical devices that are already on the market. This information should be used to reduce the potential user errors that can occur with the medical device being manufactured.

Other forms or methods of evaluation of the device can utilize expert reviews and heuristic analysis to identify weaknesses in the device design and establish modifications to reduce user errors.

Empirical approaches to identifying use-related errors may also be helpful by gathering data from representatives of the intended users. Observing the representatives interacting with the device and asking questions about why decisions are made can help the manufacturer when designing a medical device for specific tasks. Interviews can also provide valuable insight to known problems with a device and to possible solutions. These evaluations are beneficial during the design phases because it can allow the manufacturer to make modifications before the device goes to market.

Eliminate or Reduction of Use-Related Hazards

User-related hazards identified in the preliminary evaluations should be reduced or eliminated as much as possible during the final development stages of the device. This can be done by modifying the design of the device to remove the hazards, incorporating protective measures in the device to avoid the hazards, and by providing safety instructions and clear training for intended users. It is important to continue to reassess the device after each evaluation and modification to ensure that the user-related hazards were addressed correctly, and new hazards were not created.

Validation

Human factors validation testing should be performed to show the device can be used by intended users, for the intended purpose, and under the intended conditions, without user errors. This testing should be sensitive enough to capture user-related errors, even if the user is not aware they have made them. The user should be able to use the device as independently and naturally as possible, without any interference or guidance they would not normally have during actual use. The validation should also show that all user-related hazards have been reduced or removed during the development stages of the device. Information gathered during the preliminary analysis of the device is used to guide the validation testing.

The validation test participants should represent the variety of characteristics of each of the intended user populations. These characteristics should include considerations such as age, functional limitations, and previous experience. Similarly, the tasks performed during the validation should include the full range of critical tasks defined in the preliminary evaluations.

Generally, human factors validation testing should be done under simulated conditions, but on occasion, the validation can be performed during actual use or as part of a clinical study. This should only be done when simulated-use test methods are not able to allow adequate evaluation of the users and the device.

Conclusion

Incorporating human-use factors into the design of a device is a process that should be considered from the beginning of the manufacturing phase. Reducing and eliminating user-related hazards can greatly improve the safety and efficiency of the device. Best practices include performing a preliminary risk management evaluation, modifying the design of the device to eliminate as many hazards as possible, and conducting human factors validation testing.

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