MedTech Update

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.


Alternatives To In Vivo Biocompatibility Testing

Reconstructed human epidermis (RHE) for in vitro skin irritation and sensitization testing.

Reconstructed human epidermis (RHE) provides an accurate and reliable test system for in vitro skin irritation and sensitization testing.

By: Daniel Olsen, Senior Laboratory Analyst II, Nelson Laboratories

The landscape of biocompatibility assessment of medical devices is an ever-changing and evolving one. Recently, there has been a lot of effort put into the development of alternatives to in vivo biocompatibility testing. Expanding technological capability and increased scientific understanding of the key events in complex biological responses is making this shift to in vitro alternatives possible by enabling the development of accurate, sensitive, and reliable test methods.

Because of the large amount of toxicological data available and increased sensitivity compared to animal tests, the advanced chemical characterization of medical device extractables is largely being seen as a potential replacement for many in vivo systemic toxicity endpoints. This is reflected in Figure 1 of ISO 10993-1, which lists chemical characterization as a first step in the biological evaluation of a new medical device.

Another area that is making great progress in the transition to in vitro alternatives is that of skin irritation and sensitization testing. A number of in vitro test methods for assessing skin irritation and sensitization have been validated and approved for use in chemical, cosmetic and pharmaceutical testing1-3. Many of these methods are being successfully adapted for use in medical device assessment. The final preparations are currently underway for a round-robin validation of in vitro skin irritation testing for medical devices. In addition, recently published research shows promising results for in vitro sensitization using medical device extracts4.

Nelson Laboratories is committed to scientific advancement and is actively engaged in research to assist in the development of safe and reliable in vitro alternative methods. We believe that this transition will be largely beneficial to medical device manufacturers, testing laboratories, and end users.

For more information on these important developments Daniel recommends you read Evaluation of an In Vitro Human Dermal Sensitization Test for Use with Medical Device Extracts, Better Animal Testing Alternatives Are Coming to U.S., and review Nelson Labs’ 2015 SOT poster presentation, Extractable Positive Control for In Vitro Skin Irritation Testing of Medical Devices.


  1. OECD. Test No. 439: In Vitro Skin Irritation.  (OECD Publishing).
  2. OECD. Test No. 442C: In Chemico Skin Sensitisation.  (OECD Publishing).
  3. OECD. Test No. 442D: In Vitro Skin Sensitisation.  (OECD Publishing).
  4. Coleman, K. P. et al. Evaluation of an In Vitro Human Dermal Sensitization Test for Use with Medical Device Extracts. Applied In Vitro Toxicology 1, 118-130, doi:10.1089/aivt.2015.0007 (2015).

In Vitro Skin Irritation Breakthrough To Revolutionize Medical Device Testing

Extractable Positive Control for In Vitro Skin Irritation Testing, SOT 2015

New research on extractable positive control for in vitro skin irritation testing of medical devices presented at 2015 Society of Toxicology (SOT) annual meeting. Click here to download in vitro skin irritation PDF poster.

Scientists at Nelson Laboratories recently returned from presenting new in vitro research at the 2015 Society of Toxicology (SOT) annual meeting with news that the future of in vitro testing of medical devices in the United States looks bright, and closer than previously anticipated.

Invited to present information about their discovery of, and subsequent research on, an extractable positive control material for in vitro skin irritation testing of medical devices, this breakthrough may offer the data FDA has been waiting for.

Nelson Laboratories, along with strategic partners throughout the world, have been developing and validating this alternative in vitro skin irritation test method for a number of years. Skin irritation is a condition caused by acute damage to keratinocytes following exposure to a chemical. Testing for the skin irritation potential of medical devices has typically involved the use of laboratory animals.

While in vitro skin irritation test methods have historically been shown to provide results consistent with in vivo data, they have involved the use of chemical solutions or spiked extracts as positive controls. To provide a method that more accurately mimics in vivo medical device testing methods, in which devices are extracted in polar and non-polar solvents, in vitro research has been focused on discovering an extractable material that will induce a positive skin irritation response in both polar and non-polar extraction vehicles.

Nelson Laboratories’ discovery that heat-pressed polyvinyl chloride (PVC) sheets infused with Genapol X-080 act as an irritant in both polar and non-polar fluid is a major step forward toward regulatory acceptance of this method. Nelson Labs is working closely with regulators to usher in this new era of medical device testing.

Download Nelson Labs’ SOT poster presentation to learn more about the scientific data behind Nelson Laboratories’ in vitro findings. You also read Nelson Labs’ press release, Scientists at Nelson Laboratories Discover Extractable Positive Control for In Vitro Skin Irritation Testing of Medical Devices.

Nelson Laboratories President/CEO Jeffery Nelson Talks MedTech With

Jeffery Nelson President/CEO Nelson Laboratories

Jeffery Nelson, President/CEO Nelson Laboratories

Nelson Laboratories President and CEO Jeffery Nelson recently met with MDTmag’s Sean Fenske to discuss the future of the MedTech industry. The following is an excerpt from that interview in which Nelson highlights the state of medical device testing in light of the novel and innovative products coming to market.

Visit for the complete interview.

What are some significant changes you’ve seen in the medical device development industry since your start in this market?

Nelson: I’ve watched as our industry has gradually matured. I remember in the early years of the company, we were often working directly with founders of smaller companies. Even larger manufacturers were represented by an engineer or quality assurance person. Over time, this has changed, and we are now interacting with more buyers, purchasing agents, and outsourcing coordinators, many of whom are managing multiple sites or divisions. This can result in some efficiency, like shared audits, and centralized communication, but definitely changes the interaction and communication with our customers. In some cases, we are beginning to see the use of electronic bidding processes. These auction type approaches can definitely drive down price, but don’t always consider the significant costs that can accrue beyond price if quality is compromised.

…. I see more opportunity than ever before in our space. Today, professionals in our industry can follow any number of development paths in building a successful, long-term career. It is a great time to be working in this industry.


It’s also exciting to see how innovative our industry is. There are so many new and novel products. We see more hybridization of products, incorporating pharmaceutical, technology, and even tissue elements. Our industry has amazing engineers and technologists who are pushing the frontier of medical science. Although exciting, this does create new challenges. How do you sterilize a medical device that now has a heat labile pharmaceutical component? How do you apply the tried and true consensus standard to a novel product like this? These challenges require more flexibility in the standards that govern testing and more creativity by the manufacturers and laboratories that produce and test these products. It’s more important than ever that manufacturers receive timely advice about how to proceed and carefully document their decisions and justifications. We are consistently seeing more demand for help in this area. Companies who contact us don’t just need tests performed, they need a partner who can help them make decisions, justify and document these decisions, and be there for them when they have to defend the decisions in the courts of regulatory scrutiny.

For the complete interview visit

2013 MedTech retrospective

For the MedTech industry there was a mixed bag of results, innovation and regulatory changes.  Venture capital has not returned to pre-2008 levels in most medical technology sectors, the medical device tax in the United States was widely debated by industry, US Congress and the news media.  I found the following reports helpful in understanding this mixed bag.

AdvaMed summary of cuts and taxes impacting medical industry (Aug 2013)

PWC – Q3 2013 report illustrates the funding landscape, top metropolitan areas for investing in biotech/medtech.

Author: John S. Bolinder |