The U.S. Environmental Protection Agency (EPA) issued a data call-in (DCI) for the ingredient para-tertiary amylphenol (PTAP) in December 2018. PTAP was the active ingredient in several popular registered facility disinfectants. It contained antimicrobial properties but became toxic when swallowed or inhaled and corrosive when in contact with skin or eyes, according to the National Institutes of Health’s Center for Biotechnology Information.
The EPA required active ingredient manufacturers to reformulate their products, remove the ingredient, or prove their PTAP-based products were safe. The environmental agency requested that PTAP manufacturers supply additional data that would demonstrate the product’s safety. When manufacturers decided against generating new studies, the EPA mandated a full phase-out by mid-2020. Medical device manufacturers using affected products would need to switch to alternative disinfectants, requiring efficacy revalidation.
Medical device manufacturers are responsible for meeting and maintaining hygiene requirements for all working surfaces at all facilities. The PTAP story is just one example of what happens when regulations change and previously unrestricted products are deemed dangerous. It’s the reality of medical device manufacturing when patient safety is (rightly) the top priority. Creating safe and effective medical devices is a precise and time-intensive process—not to mention a significant investment. Facilities, equipment, research, development, manufacturing and packaging all combine to provide products that support patient safety. But overlooking microbial control can derail all of it. Working with a laboratory partner to execute well-designed, compliant revalidation testing on products and facilities can ensure patient safety and support regulatory success.
What to expect when your product is discontinued
First, don’t panic. The EPA and other regulatory bodies generally provide a phase-out date for problematic products. In PTAP’s case, the EPA gave manufacturers almost two years to use up their supply of the discontinued disinfectant. It is uncommon to have a product that requires immediate removal.
But you will need to start revalidating any new sanitation process of surfaces. Properly sanitizing a facility is a complex and extensive process. Your timeline will depend heavily on the number of organisms for which you need to test, the surfaces you need to sanitize and access to your newly chosen disinfectants. You also must provide, in detail, whatever cleaning products are in place. Manufacturers are responsible for communicating these details to laboratory testing partners, but the communication shouldn’t stop there. Any time a company moves into a new facility, expands an existing one, adopts a new cleaning process or product, or sees a change in organisms during environmental monitoring, it all needs to be revalidated to ensure contamination control, which impacts product safety.
Validating any disinfectant comes down to a combination of variables, including:
- Organisms recovered from a product or facility
- Environmental factors
- Surface material
- Cleaning process
- Contact duration
- Hold time
These variables, and the sequence in which they are tested, measured and documented, form the protocols for disinfectant efficacy testing (DET). The process requires analyzing two-inch by two-inch material slides (i.e., coupons) taken from surfaces within facilities. The coupons are sterilized prior to testing and then inundated with organisms from American Type Culture Collection (ATCC) organizations—or equivalent bodies—environmental isolates or sterility and bioburden samples. The goal is to understand the organisms present and validate that the disinfectants and protocols in place promote a safe environment. Put simply, DET will tell you if your cleaning regimen is appropriate for the organisms in your environment.
If you change one of the variables in the combination, you’ll have a new sequence that will need testing and validation. For example, when the EPA discontinued PTAP-based disinfectants and required device manufacturers to choose an alternative product, it added a significant new variable to the sequence.
Can manufacturers speed up the revalidation process?
In a word, no. Depending on the number of variables in a specific combination, DET scientists cannot speed up testing and still maintain the integrity and thoroughness of the process. It can take months to validate a single sanitizer, depending on the number of surfaces, organisms, and applications tested. That said, if a manufacturer is in a time-sensitive situation, there are things laboratory partners can do to prioritize combinations or stagger test results to provide the most important information in the timeliest fashion.
Divide and conquer
It is possible to break large, comprehensive DET programs into smaller, more focused tests. It’s also possible to test one variable—e.g., sanitizer, surface, cleaning process, etc.—at a time. Both options are ideal if a manufacturer has data from a previous DET program and only needs supplemental information to achieve compliance.
STAT testing
Laboratory partners often have high-priority testing options for manufacturers who might have overlooked early problems and now need help in a hurry. While it may be a more significant investment, it can help you get back into regulators’ good graces and have your facility up to speed from a safety standpoint. Manufacturers that are tight on time can also receive step-by-step test results or simply focus on the worst-case organisms and validate the rest during later testing.
Advice for manufacturers seeking revalidation
It may be tempting for manufacturers to look for ways to save time and money on DET by combining testing for various locations. But this approach doesn’t work. Each site has unique variables that will impact DET, and applying results haphazardly can lead to regulatory non-compliance and potentially an audit finding. A better approach is to send coupons and organisms from each location and, if necessary, prioritize the most critical ones.
It’s also crucial for manufacturers to continuously evaluate their environmental monitoring procedures. Changes in the environment, new staff or surfaces in the facility, or rewritten standard operating procedures (SOPs) can all contribute to a need for revalidation. Manufacturers should also perform DET if they detect a shift in the organisms recovered during environmental monitoring, especially recurring ones. Ensuring that processes are being followed as procedures are updated is one way to keep facilities compliant and safe.
A final word on revalidation
In the world of DET—where it can take months to revalidate a single sanitizer—time flies. Waiting to revalidate your disinfectant processes until you experience a safety issue or have an audit finding can necessitate an uncomfortably fast process and a big headache.
Get in front of any DET requirements by proactively reviewing your procedures, organisms, surfaces and existing validation data. And keep in mind, the people ordering supplies in your facility aren’t always who uses them or vets their efficacy. Revalidation is a vital way to keep facilities compliant and patients safe.
Interested in disinfectant efficacy testing? Check out all of WuXi AppTec’s microbiology capabilities.
WuXi AppTec provides a broad portfolio of R&D and manufacturing services that enable companies in the pharmaceutical, biotech and medical device industries worldwide to advance discoveries and deliver groundbreaking treatments to patients. As an innovation-driven and customer-focused company, WuXi AppTec helps our partners improve the productivity of advancing healthcare products through cost-effective and efficient, socially responsible and sustainable solutions. With industry-leading capabilities such as R&D and manufacturing for small molecule drugs, cell and gene therapies, and testing for medical devices, WuXi AppTec’s open-access platform is enabling more than 5,200 collaborators from over 30 countries to improve the health of those in need – and to realize our vision that “every drug can be made and every disease can be treated.”
