Process Validation

FDA Safety Notice: Lubricious Coating Separation on Intravascular Devices

Recently the US FDA issued a safety notice on Lubricious Coating Separation from Intravascular Medical Devices.

The FDA wants to make health care providers aware of the possibility that hydrophilic and/or hydrophobic coatings may separate (e.g., peel, flake, shed, delaminate, slough off) from medical devices and potentially cause serious injuries to patients. Coating separation can be caused by a number of factors, ranging from the difficulty of the procedure and the patient’s anatomy to practitioner technique or using the wrong device for the procedure, to improper preconditioning of the device and improper storage conditions as well as issues with device design or manufacturing processes.

This highlights the need for intravascular medical device manufacturers to perform simulated use testing on these devices, specifically looking for particulate matter.  Nelson Laboratories can assist customers with these tests.

FDA Safety Communication Date:  23 November 2015

To learn more visit:

Tribute to Dr. Scott Sutton; Review of Bioburden Contamination Control

Scott Sutton, PhD, was a well-respected and influential thought leader in the microbiology industry. He was a consultant and trainer in CGMP, investigations, environmental monitoring, and contamination control for pharmaceutical companies for over 30 years. He gave many presentations on these topics, and received multiple awards for his publications in microbiology journals and industry trade publications. For the past 22 years, Dr. Sutton served on the United States Pharmacopeia committee on Microbiology, serving as Vice-Chair from 2000 through 2010.

Dr. Sutton passed away on October 19, 2015. Shortly before his passing, Dr. Sutton published an article regarding the process of controlling bioburden contamination in a manufacturing facility. In memory of this great contributor to the microbiological and pharmaceutical industries, we have highlighted a few key points from this recent article. To read the full article by Dr. Sutton, please click here.

Bioburden contamination is an aspect of product manufacturing that must be considered for all medical devices and pharmaceuticals. Processes to attempt to control the contamination through validations and monitoring in each phase of production should be in place to ensure the bioburden contamination remain at an appropriate level. Maintaining control of the bioburden is far too complex for a single individual or even department to accomplish by themselves, so training and adherence to these processes is vital in ensuring any bioburden contamination stays at a manageable level.

Building Design & Control: Bioburden control in a facility should optimally begin with the design and construction of the building. Areas in a facility that are able to be tightly controlled should be surrounded by areas that are not as easily controlled. An important part of this design is the placement of air filters to ensure the pressure differential between areas allows the aseptic air to be pushed out. An argument can be made that the placement of filters in a terminal location allows for better air cleanliness, however, the ease of monitoring and maintenance should also be considered when placing filters. Facilities should also be designed to prevent personnel and materials from using the same paths to minimize cross-contamination. This type of building design works best when airlocks and pass-through chambers are put in place, as they help maintain bioburden barriers.

Water Systems: The water system of a facility also contributes to the control of bioburden contamination in a building. The properties of water make it an easy avenue for microbial contamination. Because water is often used as a raw material and a utility, frequent maintenance and monitoring are necessary to contain the bioburden resulting from the use of water. The last design element Dr. Sutton discusses is the location of the product when it will be at its most vulnerable point in the manufacturing process. Protection of the environment around the product at this point by an isolator or other environmental controls aids in maintaining control of the bioburden.

Equipment: Once the design of the facility is in place, the next factor to analyze is the equipment being used. In addition to the tasks the equipment is required to perform, the ability to clean and sanitize the equipment should also be considered. Choosing equipment and placing it in locations that allow for easy cleaning and sanitation aids in the exclusion of microorganisms from coming in contact with the product. Fill lines and equipment should also be organized in a way that will not allow for mix-ups or cross contamination between filled products and raw materials. One way to minimize contamination is to eliminate the human factor, and utilize equipment to fill the product.

Cleaning Processes: The sporicides and sanitizers that are used in bioburden control processes need to be tested to show their efficacy against the microorganisms in a facility; generally, this is a four-step process. The first step is a suspension test. This test analyzes the effectiveness of a sanitizer against indicator organisms as well as other organisms found in a facility. This test aids in selecting the best sanitizer for your product and also determines the most resistant microorganism. The second step is a coupon study, performed on materials present in the facility. This study evaluates the effectiveness of the chosen sanitizer against the organisms found in the suspension test. The third step is a “mock” sanitation study to provide real-world analysis of the effectiveness of the sanitizer. The last step of testing the sanitizer is ongoing environmental monitoring. This is usually done by the annual trending of the environmental monitoring to show the bioburden is being adequately controlled.

Personnel: The main source of bioburden contamination during manufacturing process comes from the personnel involved. It is estimated that an individual at complete rest sheds about 10,000 particles per cubic meter. Any movement or activity increases this number exponentially. Because of this, it is important to be careful in selecting gown material and also gowning methods. Simulated trainings, proficiency testing, and monitoring of the operators and their involvement in the manufacturing process are vital to make sure human contamination of the product is limited. Use automation in manufacturing to avoid the chance of mix-ups causing cross-contamination and limit the need for human intervention. To assist in monitoring the bioburden in these processes, bioburden testing should be performed on all material coming into a facility, and checked against existing bioburden acceptance criteria prior to use.

Process Monitoring: Monitoring activities and processes to control bioburden are indirect, so it is important to partner with a reputable testing facility that is knowledgeable on current industry standards in creating and carrying out these procedures. USP has recently released a chapter to help break down laboratory operations into a series of systems, that when paired with other USP chapters are useful in determining the best practices for a facility.

Thank you, Dr. Scott Sutton, for your contribution to the microbiology community.


Need Additional Guidance? Nelson Labs employs many scientists who actively participate in the creation and modification of industry standards who can help interpret the standards and apply them to specific products and facilities.


Nelson Laboratories Scientist Provides Clarification on Tissue Bank Cleaning Validations

Alpa Patel, Nelson Laboratories Senior Scientist - Healthcare Reprocessing

Alpa Patel, Nelson Laboratories Senior Scientist – Healthcare Reprocessing

Nelson Laboratories, Inc. Alpa Patel, senior scientist in healthcare reprocessing, presented at the annual American Association of Tissue Banks (AATB) meeting last month on the topic of Equipment Cleaning and Disinfection Validations, something she calls, “the tissue industry’s compliance challenge.

Highlighting regulatory issues and solutions for process validations at tissue banking facilities, Patel noted, “Because tissue is an emerging industry they have had less experience with validations than other MedTech service providers and may not know what to expect.”  However, recent regulatory attention on the cleaning, disinfection, and sterilization validations for the equipment and supplies used to process tissue is changing that.

“While the FDA does not clearly state the requirements for these validations, recent trends have shown that companies that state they adhere to the American Association of Tissue Banks (AATB) standard may be required to have a validation plan in place.” said Patel. “And although the Good Tissue Practices (GTP’s) do not specify these validation practices, there is good reason for tissue banks to acquire them.”

Intimately involved in assisting some of the world’s premier tissue banks in establishing their validation plans, Patel recommends tissue banks review whether or not an equipment validation plan is in place and take appropriate measures to ensure compliance sooner rather than later since:

  • Regulators have begun auditing some tissue banks.
  • Facilities that did not have validation data to support the cleaning, disinfection and sterilization of their equipment have been issued observations.

Patel reminds us “The real value of a process validation for equipment used in tissue processing is that  validated cleaning, disinfection, and sterilization processes help ensure the absence of cross contamination between donors during tissue processing.”

To learn more read Equipment Cleaning, Disinfection, and Sterilization Validations – The Tissue Industry’s Compliance Challenge!, and Importance of Cleaning and Sterilization Validations, Even When They May Not Be Required.

You may also contact Nelson Laboratories at, 800-826-2088, or

Importance of Cleaning and Sterilization Validations, Even When they may Not be Required

By Alpa Patel, Department Scientist-Healthcare ReprocessingCleaning-Process

I recently attended the 10th Annual FDA and Changing Paradigm for HCT/P Regulation Conference, with my colleague Wendy Wangsgard, Department Scientist, Bioburden. We presented topics of interest that have surfaced the validation realm, in addition to learning updates from the FDA.

At this conference, the FDA presented new R&D data on new developing assays, news on current and retired tissue establishments, and important events that occurred during the last year within the tissue industry. These updates include reviews of tissue products, recalls and information on how to prepare a response to recalls.

My presentation focused on cleaning validations on equipment and supplies used for tissue processing. This included when validations are needed and why it is important to perform even if the FDA does not require these validations at this time.

The two key points when a validation is essential are:

  • When a new process is introduced: It is necessary to validate new processes to ensure the procedure is adequate for cleaning and sterilizing.
  • When there is a change to the process: Changes to the process can include steps of the process, a change of disinfectants/detergents, and new equipment.

Validations are necessary to ensure the process is effective and all equipment and supplies are free of contaminants after the cleaning process. Validating also ensures consistent process capability, meaning each time a device is cleaned, you know it is consistently cleaned to the required and safe level.

Cleaning validations are important, even when not required, to ensure safety through cleanliness. Validating the cleaning, disinfection and sterilization processes lowers the risk of cross-contamination between donors since the tissue-processing equipment and supplies that are used between donors are clean and sterile.

Validations for sterilization and cleaning, while not always required but are extremely important for manufacturers to consider. Validations are one more step that helps ensure the safety of the reusable equipment and supplies used to process donors every day.

Other highlights from the conference include:

  • Details from the FDA’s Draft Guidance Document
  • Classifications for recalls
  • Guidelines for adverse reaction reporting
  • How to prepare an FDA response

AAMI Sterilization Standards Meeting Update on Processing of Reusable Medical Devices

Medical-device-cleaingBy Emily Mitzel, Laboratory Manager

On April 14-16, 2014, I attended the Association for the Advancement of Medical Instrumentation (AAMI) semi-annual Sterilization Standards Meeting. These Association meetings, and the standards discussed during them, have a major impact on medical device manufacturers, testing facilities, HCF managers, and the FDA.

Processing of reusable medical devices is an extremely hot topic with manufacturers and regulators.  Many working groups, standards, and technical informational reports are currently being written and revised by the AAMI and ISO committees.  We are very involved in all of the meetings and document updates.

Highlights from the meetings include:

  • AAMI TIR34 – Water for the Reprocessing of Medical Devices – This document will be submitted for final 30-day review this summer.  The categories of water have changed, so medical device manufacturers may want to use these categories in their IFUs as this is the quality of water that the healthcare facilities will use for their reprocessing.
  • AAMI TIR55 – Human Factors for Device Reprocessing – This document is going to ballot for the first time.  It is a great document designed for medical device manufacturers to provide guidance from a human-factors perspective.
  • AAMI TIR63 – Management of medical devices that are not owned by the healthcare facility where they are used – This document is now going to ballot after successfully responding to all of the comments provided for the last meeting.  This document will help manage medical devices that move between healthcare facilities.

Process Validations for Newly Manufactured Devices – Is Your New Device Clean?

During the two-day BIOMEDevice Boston conference and showcase Alexa Tatarian, Material Characterization and Process Validation Scientist at Nelson Laboratories, presented at the Tech Theater on Wednesday March 26th at 1:40 pm. She presented Process Validations for Newly Manufactured Devices – Is Your New Device Clean? to help manufacturers understand how to properly monitor and assess the cleanliness of their finished product and key factors that affect cleanliness during the manufacturing process. Here is the video of that presentation.