US FDA Reprocessing Expectations

By Sarah Fitzgerald

Medical device regulators around the world are encouraging coordination and regulatory consistency. From a high level, virtually all medical device regulators take a risk-based approach and require that the benefits of the medical device outweigh the risks before authorization. However, detailed expectations are not yet consistent. The United States (US) Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) has three main areas with expectations that are usually significantly different from most other regions of the world. These areas are biocompatibility, reprocessing (cleaning, disinfection, and/or sterilization), and cybersecurity.

Background on reprocessing

Reprocessing is the process of making a device ready for use between uses. If adequate reprocessing is not conducted, infections could be transmitted. Although not all hospital-acquired infections (HAIs) are transmitted through inadequate reprocessing, it is believed that this contributes or causes many cases. In the US, an estimated 687,000 HAIs occur annually and about 3% of hospitalized patients experience an HAI. Additionally, about 72,000 patients with HAIs died during their hospitalizations, although not necessarily because of the HAI itself. Therefore, it is clear that reprocessing is important to the overall safety of a device.

Depending primarily on the contact type in alignment with the Spaulding Classification, and potentially influenced by factors such as if the device is intended for single-patient use or the likelihood of contamination, cleaning, disinfecting, and/or sterilization may be required before the device can safely be next used. Per the Spaulding Classification:

• Critical contact devices are those that are introduced into the bloodstream or contact a normally sterile tissue or body space. Examples include surgical instruments, biopsy instruments, and certain endoscopes like arthroscopes. 
• Semi-critical contact devices are those that contact intact mucous membranes or non-intact skin. Examples include respiratory equipment like endotracheal tubes, diaphragm or vaginal rings and fitting rings, and certain endoscopes like bronchoscopes.
• Non-critical contact devices are those that only contact intact skin or that are not intended to contact the user or patient. Examples include blood pressure cuffs, stethoscopes, and hospital beds. 

Note that the Spaulding Classification is not about how critical the intended use of the device is but rather the contact type. The following table provides the general expectations related to reprocessing based primarily on the contact type. 

Table 1. General Reprocessing Expectations Based on Spaulding Classification Contact Type

Overview of reprocessing and regulators 

All regulators consider the risks related to a device being able to be reprocessed to be important from the aspect of safety and expect labeling to provide instructions for reprocessing in alignment with ISO 17664-1. Additionally, when sterilization is required, sterilization validation or a summary of such is expected to be provided for review in accordance with an appropriate standard, which standard is applicable is dependent on the sterilization method. 

Note on terminology: ISO 17664-1 refers to processing. This term is considered to include reprocessing of devices between patient uses and initial processing to make the device suitable for use on a first patient. 

Reprocessing and the US FDA versus other regulators

While all regulators consider reprocessing to be an important aspect of overall safety, the US FDA expects significantly more information than most regulators to validate reprocessing. The FDA published a guidance document related to reprocessing to help manufacturers understand their perspective on reprocessing evaluation and testing. This guidance document references AAMI TIR 12 regarding designing and testing for reprocessing and AAMI TIR 30, which has since been replaced by AAMI ST 98, regarding cleaning validation specifically. The following table provides an overview of what is usually expected related to reprocessing. In some cases, whether full reports or a summary only is expected depends on the device type. 

Table 2. Reprocessing Evidence Expectations

Additional information on some of the major differences are provided below. 

Reprocessing Labeling 

Generally, the expectations related to labeling are similar between most regulators, including the US FDA. 

Reprocessing Validation: Device Based

The FDA expects that validation testing is conducted using the actual device in its worst-case condition related to reprocessing (usually, but not always, end-of-life). 

It is important to note that the FDA does not accept that the labeled effectiveness for a marketed cleaning or disinfecting agent is sufficient, unlike most other regulators. It is important to note that there are increasing requirements from low-level to intermediate-level to high-level disinfection and from disinfection to sterilization. The FDA believes it is necessary to demonstrate that the agent works on the specified medical device in the worst-case condition. In general, most other regulators only require this for sterilization. 

Additionally, the FDA expects that compatibility of the device with the reprocessing agents and instructions demonstrates that the device can adequately withstand the process throughout its intended use life. This also is not usually required by most regulators.

The FDA guidance provides a list of devices for which they would expect a full report for the above testing to be included in the appropriate submission, where devices with a higher perceived risk require the full report be provided. Generally, these are semi-critical and critical contact devices. For devices not included on this list, generally non-critical contact devices, a summary of the testing only is expected.

For semi-critical and critical contact devices, the FDA expects that biocompatibility be conducted after multiple simulated reprocessing cycles to address if residual reprocessing agents, as well as the device itself, could cause issues related to biocompatibility. This also is not usually required by most regulators.

Reprocessing Validation: User-Based

In addition, user-based validation, which can be part of formal human factors or usability testing per IEC 62366-1 or separate, is expected to be conducted for reprocessing. Specifically, this must cover both that users understand the instructions and that users can feasibly comply with the instructions. For example, if a user knows that they should disassemble a device but is unable to physically disassemble the device, this would not be acceptable. As with device-based reprocessing validation, whether a summary or the full testing report is required is based on the perceived risk. Most other regulators require that a company consider what critical tasks are from a user-based perspective and include those in human factors or usability testing, and reprocessing may be included if it is considered a critical task, but is not generally expected or required. 

FDA versus Other Regulator Expectations Discussion

To summarize, the FDA is generally considered to have the most stringent expectations for evaluation and testing for reprocessing. While labeling expectations are generally aligned between regulators, the FDA expects device and user-based validation and that summaries or full test reports of this validation be provided for their review, depending on the overall FDA perceived risk of the device contributing to transmission of infections. Therefore, even if a device has already been authorized by other regulators, the FDA may require significant additional reprocessing testing to satisfy its requirements. This can be challenging for manufacturers to understand initially and can jeopardize submissions as the FDA only allows a limited time to respond.

Minimizing risk of FDA not accepting reprocessing

There are a few manners to minimize the risk that the FDA will not accept the reprocessing evaluation and testing provided. 

First, a manufacturer should carefully consider if the evaluation and testing that they have conducted in relationship to reprocessing is in alignment with FDA guidance documents. Full validation testing is expected for all medical devices, even though for many devices only summary information on this testing needs to be reviewed by the FDA. 

Second, if a manufacturer has questions related to the acceptability of their data, even data that has been accepted by other regulators as sufficient to address reprocessing, they may wish to consider formally reaching out to the FDA via a Q-submission to obtain FDA feedback. It is important to note that a Q-submission is not intended to be a pre-review of a submission, but it is acceptable to summarize evaluation and testing and ask for FDA feedback. 

Concluding remarks 

Reprocessing is one of the three main areas where the FDA frequently has expectations that do not align with the expectations of other regulators and where even if a device has already been accepted in other regions, additional testing may be necessary. Manufacturers should carefully consider reprocessing before making a premarket submission to reduce the chance of the submission being rejected by the FDA.