A wealth of knowledge was gained from a historic data review of radiation dose verification failures. Our experts highlight the importance and application of this data set as well as its benefit to device manufacturers.
In last week’s blog post, we highlighted the importance of bioburden monitoring, both quantitatively and qualitatively, as supportive evidence for a valid radiation dose. We arrived at this conclusion through a historic data review of verification dose experiments.
WuXi AppTec Laboratory Testing Division compiled and reviewed 60 randomly selected verification dose experiments performed over a 10-year period that yielded positive sterility results with confirmed genus and species identifications. Testing consisted of a wide range of medical devices, biologics and tissues processed with verification doses ranging from 2.6 to 18.8 kGy.
After exposure to the verification dose, the products were subsequently tested for sterility. Resulting sterility positives from both passing and failed verification dose experiments were identified using biochemical, MALDI TOF MS or DNA sequencing analysis. The data analysis identified the most prevalent survivors and compiled them into a list of top surviving genera.
The top genera were further separated by organism type, such as spore and non-spore formers, and other defining characteristics such as pigmentation to emphasize additional characteristics of survivors:
|Survivors from Verification Dose Experiments: Top 8 Genera
||Occurrences in 60 Verification Dose Experiments
||Pigmentation of Recovered Isolates
||Gram positive spore forming rods
||Gram positive spore forming rods
||Gram positive cocci
||Gram negative rods
||Gram positive spore forming rods (obligate anaerobes)
||Gram negative coccoid rods
||Gram positive spore forming rods
Having analyzed data collected over a 10-year period, we have a unique perspective on the types of organisms demonstrating resistance to radiation. This information can be valuable for manufacturers looking to identify adverse trends in viable environmental samples and product bioburden data to prevent costly radiation dose verification failures.
This type of data can be used to evaluate bioburden and the associated manufacturing process. Performing microbial identification and trending of all sterilization dose verification survivors, including passing results, may reveal potential shifts in bioburden types and resistances that might not be apparent with quantitative bioburden data alone.
Clients who work with our microbiology experts are able to leverage the experience we have from testing thousands of devices. Our scientists draw from their previous studies, international standards and current regulatory environment to report results and strategize with our clients when adverse trends occur.
For more information about how you can leverage the knowledge and experience of our microbiology experts for your product testing needs, contact us
WuXi AppTec’s robust approach to microbial identification (ID) testing surpasses the industry standard offered by other laboratories.
Our clients come to us when a microbial excursion has occurred. Understanding what the microbial contaminants are, and where they have been introduced into the manufacturing process, is critical in determining the root cause of the microbial excursion, as well as effective corrective actions to prevent re-occurrence. In the manufacturing process, microbial contaminants may be isolated from many different locations and sources, including employees, air, water, surfaces, raw materials and even the final product. The first step in our identification process is to obtain a pure culture of any microbial isolates found. Once isolation has been obtained, we begin our all-inclusive approach to microbial identification. The following are included in our microbial ID testing:
- Subculturing to the point where a single, pure, isolated colony is obtained, as well as using two ID systems: VITEK® MS and Applied Biosystems® DNA sequencer.
We do not charge for subculturing, Gram staining or additional ID methods.
- For one price per isolate, we subculture for isolation and Gram stain, and we attempt to identify the microbial isolate up to three times using the VITEK MS, DNA sequencer or macroscopic ID for mold isolates.
We know manufacturers spend significant time and resources subculturing in-house to ensure a culture of less than 72 hours is delivered (a requirement for other labs). WuXi AppTec clients, however, do not have to send a culture that is less than 72 hours old. We perform this task and save clients resources, time and costs. In our own laboratories, we control testing processes for contamination – including microorganisms – to be compliant with the manufacturing quality system, processes, procedures and standards set for the industry. Let us show you how our experienced experts can provide a one-stop-shop approach for microbial identification.
Medical device manufacturers around the world are working to ensure their package designs are in line with the recent updates to ISO 11607, Part 1 and Part 2, and the Medical Device Regulation (MDR). Britt Jones, WuXi AppTec’s manager of package testing services, answered five key questions about the ISO 11607 revisions to help explain how they will affect your products and preclinical device safety test plan under MDR.
1. What are the goals of the revisions to ISO 11607, Part 1 and Part 2?
The changes are designed to enhance patient safety and create globalized harmonization with other standards. By putting stricter packaging requirements in place, product handling by clinical professionals will be more intuitive and contamination risk will be lowered.
2. What’s the interplay between these changes and MDR?
Updates to ISO 11607 should help with MDR compliance because the goal of the revisions is to harmonize the standards with the General Safety and Performance Requirements of the MDR. From an MDR standpoint, packaging failure or the inability to demonstrate package integrity per the revised standards could have serious business implications. Noncompliance could result in a product being pulled from market, unforeseen costs associated with package redesign and/or retesting, or brand reputation damage if packaging fails and causes a patient safety issue. While the requirements align closely, testing procedures vary. Under ISO 11607, testing will be required for manufacturers to comply; but, under MDR, retesting is not necessary unless thorough justification isn’t possible with currently available data. Because many legacy products under MDR will require more evidence than what exists in company records to comply, in most cases, testing will be inevitable with both standards. Determining the required tests for validation under ISO 11607 will involve a risk analysis under ISO 16775.
3. How will new usability requirements impact package instructions and testing?
The goal of the usability requirements is to provide clinical staff with necessary instructions for use. Instructions must identify a clear location on the package to begin opening it, provide instructions on the opening technique, and describe how to present the product into the sterile field while preventing contamination and damage to the contents. Proper instructions for use are critical to infection prevention efforts and patient safety. Also, manufacturers will now be required to complete usability studies that prove the instructions are effective and intuitive.
4. In what ways have sterile barrier system requirements intensified?
Regulators now need to see that a sterile barrier system’s configuration will remain intact and prevent the possibility of microbial contamination. Packaging should guide clinicians on how to inspect package integrity before use to ensure contents are presented aseptically. And packaging should provide clear steps for safe and proper use, so that the product remains sterile from the time the barrier is broken to when it’s used.
5. How has terminology changed with the updates?
The terminology used by various regulatory bodies has been inconsistent in the past, but the changes to terminology in ISO 11607 will finally create alignment. The language also aims to harmonize definitions with ISO 11139 and establish a globalized understanding around proper packaging, labeling practices and integrity testing. It’s important to understand that device history files and regulatory submissions are not complete without package validations. Ensuring all your devices and packaging are compliant with updated standards by the May 26, 2020 MDR deadline probably seems daunting, but you don’t have to go through the process alone. For more information or to secure your spot in line with WuXi Medical Device Testing, visit https://medicaldevice.wuxiapptec.com/contact-us/. WuXi Medical Device Testing offers testing services in St. Paul, Minn., Atlanta, Ga., and Suzhou, China.