New FDA Expectations for Reusable Device Reprocessing Validations

In March of 2015, the FDA published a new guidance document titled, Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling.  A draft guidance on the same subject had previously been issued and has been used by device manufacturers since 2011 as the leading document concerning FDA’s expectations for validating reprocessing procedures for reusable medical devices.   In terms of cleaning, disinfection and sterilization validations, the most notable modifications to the 2015 document are:

  1. A more inclusive recommendation to incorporate multiple full simulated soiling, cleaning, disinfection or sterilization cycles to assess the accumulation of soil over time. 

  2. Guidance for using the worst case “master device” to validate other devices in a product family.

  3. Emphasis on visual inspection.  Visual inspection of both external and internal surfaces should be performed. 

  4. A statement recommending that devices that become hot, such as powered hand pieces or electrosurgical instruments, be validated while hot to replicate clinical use.

  5. A recommendation that two quantitative test methods be used to test for the amount of residual soil.  The recommendation of two different methods was not present in the draft version of the document.

  6. A recommendation that the type of soil chosen be justified and if the soil deviates from FDA-recognized standards then the deviation should be justified.

  7. A more detailed recommendation of what is expected from the positive and negative controls.  The Negative Sample Control is the blank - the extraction fluid only.  The Negative Device Controls should be unsoiled and undergo the same cleaning and extraction as the test devices.  The Positive Sample Control is the extraction fluid with a known amount of soil at or slightly above the limit of quantitation.  The Positive Device Control is a device that is soiled with a known amount of soil.  The Positive Device Control is not cleaned and the soil is then extracted.  The amount of soil extracted should be equivalent to or slightly lower than the amount of soil placed on the device.  

  8. An emphasis on disassembly during the soil extraction steps in order to remove soil from difficult to access areas.

  9. A recommendation to demonstrate that cleaning solutions are not penetrating internal compartments that are not intended to come into contact with soil or fluids.

Many of the changes above had been prescribed by AAMI documents and had become standard practice within the industry, while other modifications are welcome clarifications that had not been addressed previously.  What is not included in the new guidance document is also noteworthy.  Previous communications with the FDA indicated that six reprocessing cycles would be recommended before testing for residual soil. Surprisingly, this recommendation was not included in the most recent guidance document.  The only advice given by the FDA guidance document is that the number of reprocessing cycles must be scientifically justified.

Six Full Soiling, Cleaning, and Disinfection Cycles May be Needed

Yet there is still some question as to what the FDA specifically requires. Recently, a Pacific BioLabs client contacted us for reprocessing services because the FDA had rejected the client’s disinfection validation. This validation had been performed at another contract lab, and did not incorporate repeated soiling, cleaning and disinfection cycles.  The FDA, upon review, asked this client to conduct six repetitive soiling, cleaning, and disinfection cycles.  Thus, even though the FDA did not stipulate in the most recent guidance document that six full soiling, cleaning, and disinfection repetitive cycles be conducted, it appears that the FDA is internally subscribing to the policy that reusable devices should undergo at least six full cycles.  

Pacific BioLabs performs validations of device cleaning and disinfection protocols and other medical device reuse studies.

Why Understanding Bioburden and Sterilziation is Key to Medical Device Development

Pacific BioLabs and Nutek (a contract sterilizer specializing in e-beam irradiation) work closely together to perform the microbiology and sterilization needed for medical device sterilization validation programs. In this presentation we share some of our knowledge and advice on how to ensure a successful validation, which is a key factor in a medical device development program.

Pacific BioLabs performs medical device testing including sterilization validation services

Evaluation of Immunogenicity and Allergic Reactions to Medical Device Materials and Combination Products

Collagen - an example of a biological material used as part of medical devices.

Collagen - an example of a biological material used as part of medical devices.

As devices become more complex, biocompatibility and material evaluations must necessarily become more complex and thorough as well. Allergic and immunogenic reactions are a serious safety concern not only for pharmaceuticals, but because of increasing device complexity, they are also an emerging concern for devices. In the past, evaluation of devices looked only at allergic potential (not at immunogenicity), and was done by looking for sensitization to the device itself. This testing - for a delayed-type of hypersensitivity in guinea pigs - is still required for all devices.

Complex and Novel Materials Require More In-Depth Testing

However, it has become more common to see devices comprised of engineered biomaterials (such as stents coated in collagen or using other biologically-derived scaffolds.)  Drug/device combination products pose novel immunogenicity safety concerns – for example, nano-particles often combine natural or synthetic polymers with drugs. Nano medicines such as liposomes, carbon nanotubes, dendrimers, and polymer conjugated proteins have physical, chemical, and biological properties that may attract the attention of the immune system.

These complex devices, and those containing novel materials (e.g., plastics, polymers, metals, ceramics, biological materials) or devices that are lacking adequate testing for immunotoxicity, should also be tested for additional immune responses.

It becomes important to evaluate immunogenicity because the results of an immunological response can be so serious. Immunological effects include inflammatory responses, immunosuppression, immunostimulation, or autoimmune responses.

Performing Immunogenicity Testing of Devices

Testing for immunogenicity may involve animal implantation studies followed by analysis of serum for changes in total circulating IgG, and/or antigen specific responses by ELISA.  Hemocompatibility testing should include measurement ofcomplement activation. This can be performed in vivo or in vitro.  Device material or extracts are incubated with specially handled human serum and then activated complement cascade proteins are measured by ELISA.   Alternatively, serum from animals implanted with the device can be tested for complement activation.  These bioanalytical tests provide information to manufacturers and regulators about the safety and biocompatibility of the product.

Pacific BioLabs performs immunogenicity testing, has an experienced staff, and is here to help in determining what may be needed for your device. It is important to identify early whether your device may need an immunogenicity evaluation, and to begin collecting this data along with your biocompatibility data to support your 510(k) or PMA submission.

Additional information can also be found at the FDA website, including a flow chart to determine whether immunotoxicity testing is necessary:


PBL Announces New QA Department Manager

PBL is pleased to announce that Haihong Bao has joined as the new Quality Assurance Manager.

Haihong brings more than 10 years of experience working in CRO environments, including 5 years QA management experience focusing on toxicology, analytical chemistry, and bioanalytical studies and reports.

Her previous CRO experience includes 5 years at JOINN Laboratory, a CRO in Beijing, China, 2 years at MicroConstants, and 4 years at ITR Laboratories as a Toxicologist.

Pacific BioLabs Appoints Michael Yakes, PhD as VP of Toxicology

April 9, 2015

HERCULES, California –Pacific BioLabs, a GLP/GMP pharmaceutical and medical device contract research organization, today announced the appointment of Michael Yakes, PhD as Vice President of Toxicology, responsible for all toxicology, PK/ADME, bioassay, and biocompatibility testing.

Dr. Yakes has spent 14 years in the pharmaceutical industry, directing pharmacology programs and managing multidisciplinary teams at Exelixis, and was recently the Senior Director of Translational Biology for Cleave Biosciences, overseeing toxicology, DMPK, and pharmacology studies.

“We are extremely pleased to welcome Mike to PBL,” said Tom Spalding, President of Pacific BioLabs. “Mike has an outstanding track record in the pharmaceutical industry, and brings fantastic energy and leadership skills to the position. I’m confident that our current clients will enjoy working with Mike, and that his entrepreneurial skills and business acumen will help PBL continue to grow.”

About Pacific BioLabs

Pacific BioLabs is a contract research organization providing a broad array of development and manufacturing support services to the pharmaceutical, biotech, and medical device industries. By supporting these industries through GLP and GMP testing services, Pacific BioLabs helps to bring life-saving and life-improving therapies and devices to patients who need them. Located in Hercules, CA, Pacific BioLabs operates out of a state-of-the-art, purpose-built 32,000 square foot facility overlooking the San Francisco Bay. For more information, please visit