FDA

Introduction to the Validation of Sterile Medical Devices: Sterilization, Packaging, Biocompatibility, Toxicology, and Reprocessing

For over a decade, Nelson Laboratories has been hosting educational seminars called The Science of Sterilization Validation. The aim of these three-day seminars has been to provide MedTech professionals the opportunity to establish or refresh their fundamental testing knowledge and, thereby, achieve more efficient, accurate, and effective testing outcomes.

As the needs of our customers have evolved, we have continuously updated our seminars to meet those changing needs.  To better align with the new, more comprehensive agenda, Nelson Labs is re-naming the seminar to: Introduction to the Validation of Sterile Medical Devices: Sterilization, Packaging, Biocompatibility, Toxicology, and Reprocessing. The program will continue to be RAPS and ASQ approved for 12 RAC and 1.2 ASQ credit hours and may also qualify for AAMI credit hours. Courses are taught by Nelson Labs’  and SteriPro’s scientific experts. Highlights include, but are not limited to:

  • Introduction to Microbiology & Sterilization:
    The introduction offers attendees an opportunity to brush up on the basics of sterilization, microbiology, and important industry terms.
  • Ethylene Oxide Sterilization Validation:
    Learn how to develop, optimize, and validate a successful ethylene oxide sterilization process that delivers the necessary sterility assurance level and ensures repeatability.
  • Biocompatibility / ISO 10993:
    With 24 possible categories, the biocompatibility testing experience can be intimidating. We will help you understand the testing requirements of ISO 10993 and how to choose the correct test methods for your product.
  • Chemical Characterization / E&L Assessments:
    This topic will help you understand the analytical chemistry strategies that can be used to characterize device materials and evaluate extractable/leachable compounds.
  • Packaging Overview / ISO 11607:
    Focused on the requirements outlined in ISO 11607, this subject will help you understand packaging validations and how to successfully navigate the package testing arena.
  • Radiation Sterilization Validation:
    Attendees will learn how to perform radiation validations, review bioburden data, deal with sterility test failures, and understand the various radiation options (gamma, electron beam, and X-ray).
  • Cleaning, Disinfection, and Sterilization Validations of Reusable Medical Devices:
    Our experts will teach attendees the information and processes involved in the validation of healthcare device reprocessing instructions. Highlights include discussion of the guidance documents, standards, industry trends, and the acceptance criteria.
  • Cleaning Validations for Newly Manufactured Devices and Single Use Implants:
    The importance of manufacturing clean devices will be discussed, and how cleanliness should be evaluated in addition to the sterility and biocompatibility of a device.

The full seminar is appropriate for professionals who are new in their role as well as for MedTech veterans. Lectures are presented by industry-leading experts and include case studies, hands-on activities, Q&A, and one-on-one time with the speakers. 100% of post-seminar survey respondents have expressed that they would recommend the seminar to a colleague or friend.

Visit the Seminar page on the Nelson Labs’ website to learn more about the next seminar near you.

For more information regarding our seminars, contact the Nelson Labs’ marketing department: marketing@nelsonlabs.com.

Three-Day Webinar Series: Medical Device and Pharmaceutical Testing Regulatory Updates, Trends, and Anticipated Changes

Learn from the industry-leading experts at Nelson Laboratories in the three-day webinar series Medical Device and Pharmaceutical Testing Regulatory Updates, Trends, and Anticipated Changes including FDA, ISO, USP, and MDRs.

The experts at Nelson Labs are teaming with MD+DI to bring a live three-day webinar event that provides manufacturers of medical devices and pharmaceutical products with the most up-to-date regulatory updates, trends, and anticipated changes (including FDA, ISO, USP, and MDRs). Online registration is currently available on the MD+DI website. Many of those speaking contribute to committees that provide global guidance to safeguard patient health; each webinar will offer 15 minutes for audience questions with these experts. Details for each webinar are as follows:

OVERVIEW DAY 1

Title: Assessing Biocompatibility for Medical Devices: Updates, Trends, and Anticipated Changes

Date: Tuesday, 26 September 2017

Time: 11:00 AM Pacific Daylight Time (2:00 PM Atlantic Daylight Time)

Duration: 1 hour

Summary:

This presentation will discuss the recent and upcoming changes to regulatory documents and standards and how they will impact the overall biocompatibility assessment of medical devices. The presentation will include:

  • Discussion about how biocompatibility assessments are affected by the recent updates to the ISO 10993-1 document and the new European MDRs.
  • Anticipated changes to ISO 10993-18. Since the use of chemistry in the biocompatibility assessment of medical devices is gaining traction, the document that outlines how to use chemical characterization for these assessments is undergoing major revisions.
  • An overview of changes that are expected with the acceptance of in-vitro irritation testing.
  • A thorough review of the impact of the recently finalized ISO 18562 standard which specifically targets respiratory contact devices.

Presenters:

Thor Rollins, B.S., RM (NRCM)
Director, Toxicology and E&L Consulting

Matthew R. Jorgensen, PhD
Chemical and Materials Scientist

OVERVIEW DAY 2

Title: Sterilization Methodologies and Packaging Integrity Testing: Updates, Trends, and Anticipated Changes

Date: Wednesday, 27 September 2017

Time: 11:00 AM Pacific Daylight Time (2:00 PM Atlantic Daylight Time)

Duration: 1 hour

Summary:
Sterilization methodologies and packaging integrity testing are necessary to ensure patient safety. The sterilization portion of the webinar series discusses recent and upcoming changes to regulatory documents and standards such as:

  • Changes that impact steam, radiation, hydrogen peroxide, and ethylene oxide sterilization modalities.
  • What to expect in the new ISO document for hydrogen peroxide sterilization.

As part of the packaging presentation key points regarding the new European MDRs will be reviewed, including:

  • How medical device manufacturers can collect and document objective evidence of compliance for their packaging, look at designs that prevent microbial contamination at the point of use, and justify that the package is suitable for current use.
  • An introduction to a new leak-testing technology, Mass Extraction, that demonstrates container closure integrity in a non-destructive and rapid manner, will be presented. This new test meets the deterministic requirements as outlined in the newly published USP chapter 1207.

Presenters:

Martell K. Winters, B.S., SM (NRCM)
Director, Scientific Competency

Jason Pope, B.S., ASQ CQA
Senior Scientist

Wendy Mach, RM (NRCM), CQA (ASQ)
Packaging Section Leader

OVERVIEW DAY 3

Title: Cleanliness Testing for Medical Devices: Updates and Trends

Date: Thursday, 28 September 2017

Time: 11:00 AM Pacific Daylight Time (2:00 PM Atlantic Daylight Time)

Duration: 1 hour

Summary:

This presentation will cover the latest updates and current trends for medical device cleanliness testing. This webinar will include:

  • A review of the upcoming and highly anticipated orthopedic implant cleanliness ISO document.
  • A discussion about the testing considerations for certain additive manufacturing processes.
  • Guidance updates for reusable device validations.
  • An update regarding the reprocessing of single-use devices.

Presenters:

Alpa Patel, B.S., RM (NRCM)
Senior Scientist

Alexa Tatarian
Study Director III

Paul L. Littley, B.S.E
Consulting Manager

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

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

Dr. Victoria Hitchins Remembered at Nelson Laboratories

By Alyessa D’Ewart

Victoria Hitchins, PhD, of the FDA passed away on Friday, June 17, 2016.  Dr. Hitchins was a respected microbiologist who made many contributions to the public health industry.  Emily Mitzel, Technical Consulting Manager at Nelson Labs, worked with Dr. Hitchins for over 11 years.  “Vicki was incredibly smart, personable, down to earth, and caring,” Mitzel said.  “You could always tell when she walked into the room because she greeted and was greeted by everyone.”

After obtaining her master’s and doctoral degrees in microbiology from Michigan State University, and post-doctoral studies at Princeton University and the University of Kentucky, Dr. Hitchins joined the FDA as a research microbiologist with the Center for Devices and Radiological Health.  She was a Captain of the Commissioned Corps of the U.S. Public Health Service for over 30 years; she then retired from the Corps and became the Laboratory Leader of Infection Control and a sterility consultant for the FDA.  Dr. Hitchins’ passion for public health was evident in her work outside the FDA as well.  She served as a consultant for the 2001 anthrax clean up and decontamination in Washington D.C., and participated in the 2005 Hurricane Katrina response as a Commissioned Corps officer.

During her lifetime, Dr. Hitchins authored over 70 papers and articles.  “Vicki was passionate about the research she was working on at the time, and the wheels in her brain were always spinning on the next project,” Mitzel stated.  Her research centered on the safety of medical devices, and the impact cleaning and sterilization processes have on the materials of the devices.  She provided a large contribution in developing methods for detecting bacterial endotoxins on devices and cytotoxicity testing of nanoparticles.

Dr. Hitchins was also a thought leader in the standards development process, and she served on many standards development committees.  She was the co-chair for the AAMI Sterilization Standards Committee as well as the U.S. sub-TAG for WG 16 (pyrogenicity), and was serving as the convener of ISO/TC 194/WG16 (pyrogenicity).  “I’ve worked with her on many standards committees, research projects, and client submissions.  We spoke personally about our lives, and I always enjoyed working with her,” added Mitzel.

Nelson Labs extends their deepest condolences to Dr. Hitchins’ family.  Her contributions and dedication to public health and safety will be missed.