This pilot demonstrated the feasibility of conducting remote collaborative and interactive GMP audits using a mixed reality device in conjunction with interactive text messaging. During the mock inspection, observers from multiple NRAs could interact directly with the on-site inspectors, asking specific inspectional questions, evaluating the facility, and reviewing requested documents, which allowed a remote regulatory assessment (RRA) to be conducted.

The US FDA has shown increased interest in remote assessments to help achieve oversight of regulated industries. This interest is demonstrated by the US FDA Draft Guidance for Industry: Conducting Remote Regulatory Assessments released in July 2022. The draft guidance includes new language highlighting “remote interactive evaluations” even when oversight activities are conducted by parties other than US FDA (e.g., state and foreign regulatory partners). The guidance also places emphasis that US FDA may conduct RRAs (e.g., live streaming) during these oversight activities. One additional benefit noted during the pilot program was the ability to use mixed reality to train new inspectors rapidly and effectively through real-time observation of the inspection process.

Also, it was noted by the FDA alumni inspectors that additional training on the mixed reality headset was necessary for them to be able to perform a remote audit efficiently. Also, several technological challenges were identified (e.g. wi-fi connectivity, headset battery life, etc.). That said, the technology can be used to hedge interruptions caused by a global pandemic, natural disaster, and other unstable situations allowing for inspectional continuity and consolidation of limited resources.

A survey was used to gather information from the NRAs who participated in the mock inspection. We had an 83% response rate to the survey (5 out of 6 participants). The majority of the NRA participants that responded (3 of the 5) said that the use of mixed reality was a useful tool for inspections (supplemental information). In general, the respondents appreciated the ability to collaborate with other inspectors and stated that the technology had the potential to reduce the regulatory burden of NRAs conducting individual GMP inspections. When asked about dislikes related to the mixed reality tool participants mentioned challenges with wi-fi connectivity, the need for robust training to use the headset, and the lack of battery life. Lastly, participants said they could use the information gathered from the remote inspection to write their own inspection report or partially write their own inspection report. The inspectors mentioned a pre-onsite inspection review of documents/reports (e.g., one or two weeks prior to the onsite audit) would have facilitated the writing of their own GMP reports along with the virtual inspection; in this study we did not include the pre-review document inspection. Alternatively, the onsite inspectors could review documents during the inspection and provide feedback to inspectors observing remotely.

In one-on-one interviews with the participants, these same themes were observed. Briefly, the participants highlighted the value of technology to reduce regulatory burden, improve GMP inspection harmonization, and provide an opportunity for resource-limited countries to perform their own GMP audit. Participants mentioned the utility of the technology as a training tool for new inspectors, mentioning that the technology was not only appropriate for GMP inspections but also inspection of QC (quality control) labs. In addition, it was recommended that a pre-audit readiness check be performed several weeks prior to the onsite inspection. Finally, several of the NRAs had participated in virtual audits where a company representative leads the audit using remote technologies (e.g., cell phone camera), but the NRAs preferred our approach in which a regulatory inspector (or two) would be on site to facilitate the inspection and not the company itself.

At the conclusion of the mock inspection, the company (sponsor) participants were interviewed for feedback regarding the pilot study. The primary feedback was the use of mixed reality technology could be greatly beneficial to the firm’s ability to host future remote audits or assessments with other health authorities. Also, the technology could be used to support foreign supplier qualifications/verifications where logistical challenges have arisen in the past to ensure better compliance oversight. The firm was interested in the possibility of leveraging the technology to facilitate remote training courses and/or support FDA’s remote regulatory assessments.

The mixed reality technology allows for better-resourced countries to participate in an increased number of GMP inspections, allowing for better utilization of human and financial resources, decreased redundancy of inspections, and further alignment between countries on approaches to and processes for inspections. The mixed reality technology allows for less well-resourced countries to participate in GMP inspections where they might not otherwise be able to do so. It removes the need for travel to manufacturing sites to perform an audit, thus eliminating travel costs and time spent traveling and on-site. It provides an opportunity for regulatory resource sharing and collaboration in the inspection process while still allowing each country to write their own GMP reports based on their own observations and their own national regulations and make their own regulatory decision regarding the findings.

Thus, there is a significant opportunity for the use of mixed reality devices in remote inspections. However, in-depth training is needed to ensure the headset wearer is able to use the headset efficiently. In addition, Wi-Fi connectivity is not consistent throughout most manufacturing facilities, which must be considered. Thus, participating inspectors (including those joining remotely) must discuss the procedures to follow if a loss of Wi-Fi signal occurs during the inspection. When connection is restored, it is recommended that a concise summary of events that occurred during the loss of connection be provided by the inspection lead. The lead inspector will not know when the connection is lost; this function is performed by the inspector with the mobile device.

In addition, historically, remote inspections are scheduled and have not been used for unannounced inspections. In many of these instances the remote aspect of the inspection is facilitated by an employee of the company manufacturing the drug, thus they need to be scheduled in advance to facilitate this interaction. However, in the case where the inspector performing the remote audit is from a national regulatory authority, such as in this pilot, it is possible that unscheduled remote inspections are possible.

Review of printed or electronic documentation was also a challenge using the mixed reality headset, but it is a crucial part of the audit as it can identify data integrity issues, for example [12]. We recommend requesting and reviewing copies of documentation and audit trail reports for instrumentation before the inspection.

This can be done by requesting copies of documentation and audit trail reports for instrumentation prior to the inspection. In addition, documentation can be reviewed by the onsite auditor wearing the headset in real time or after the onsite inspection. Inspectors can share their findings using the principles of regulatory reliance [13], eliminating the need to set up multiple mutual recognition agreements (MRAs) between different NRAs.