GxP Distant Assessment and Remote inspection. The point after one year of application

Mirka Broccato,
QP & GMP compliance Executive Consultant

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Mirka Broccato QP & GMP compliance Executive Consultant

Read the first part here Document and data digitisation: an essential practice for conducting GxP Distant Assessment and Remote Inspection in Pharma.

Two years after the start of the COVID pandemic that disrupted not only our lives, but also our way of working, we have learned to juggle, more or less effectively, a thousand new challenges and opportunities for change.

GMP requirements and common surveillance practices that had been established for decades and with which we had become accustomed to dealing have been strongly impacted, and have forced all players in the Life Science world to change their working methods. The same regulatory authorities have been forced to deal with the critical issues related to the impossibility of travelling and reaching the sites to be inspected, and with the even more pressing need to exercise the fundamental role of surveillance essential to ensure public health.

After two years of remote inspections, ICMRA (International Coalition of Medicines Regulatory Authorities) and its COVID-19 working group (1) analyzed the experience gained with the new remote inspection approach and summarized their considerations in an interesting reflection paper.

The members of the ICMRA group all agree that, although remote inspections have been an important tool to carry out the surveillance necessary to ensure public health in the pandemic period, they cannot be considered as a complete substitute for on-site inspections.

The limits identified by inspectors in the execution of remote inspections refer to aspects linked to the relationship between inspector and inspected (e.g. inability to read non-verbal language that often allows to create the climate of trust necessary for the conduction of an effective inspection), inability to intercept structural anomalies or to verify in a rigorous way parts of machines or rooms with difficult access (technical areas, climatic chambers…) due to the limited visual field of the video cameras. Another obstacle to the effective conduct of remote audits was the extensive presence of paper documentation and the consequent difficulty and slowness in making it available.

The level of availability of relevant documentation was also taken into account as a factor that, along with others (such as complexity of activities, type of production -sterile, non-sterile…-, compliance history), determined the authorities’ choice to proceed with a remote inspection rather than applying the traditional on-site approach.  Accessibility of electronic systems and access to original documents (e.g., SOPs, validation methods, process validation data, machine qualification data, participant medical records, signed informed consent forms, etc.) were seen as necessary factors for conducting an effective remote inspection.

The ICMRA working group found that the application and availability of the technologies needed to perform virtual facility tours (visual technologies & video streaming glasses) and to create platforms for sharing relevant GMP/GCP documents and information were key elements in the successful execution of remote inspections.

In the document prepared by the working group ((1) par 4.1.3), inspectors indicate how videoconferencing tools can also be used to review Data Integrity approaches through, for example, screen sharing of computer systems (a preferred option), data retrieval using a standalone computer, or review of exported audit trails. All of this can, of course, be applied as long as the entire process of making data available in GxP environments occurs under the supervision of Quality Assurance and that the computer systems remain in a validated state.

However, these types of inspections do not only involve the companies’ Quality departments. The inspectors’ experience has shown that the involvement of IT representatives from both sides in the early stages of logistics discussions and the execution of dry runs have been extremely beneficial, also in order to remove any obstacles related to the use of non-shared software, applications, transfer protocols that could have negatively affected the outcome of the inspection itself.

So, what can we expect in the future?

Some regulatory agencies are currently considering whether to use remote approaches in the future. There has been interest expressed by some inspectors in supplementing or replacing on-site inspection with remote inspection or hybrid approaches, e.g., to address a specific issue, contribute to an application assessment, or verify corrective/preventive actions that became necessary as a result of on-site inspections.

Therefore, after two years of remote inspections, what emerges from the inspectors’ feedback is that, although with some limitations and circumscribing the scope of the inspection, the remote approach can be considered a useful tool to enable regulatory agencies to effectively exercise their oversight role in the future.

 

(*)  The working group was chaired by MHRA and had representatives from US-FDA, EMA, Health Canada, Swissmedic, HPRA Ireland, AEMPS Spain, ANSM France, PEI Germany, MHLW/PMDA Japan, TGA Australia, ANVISA Brazil, HSA Singapore, WHO, and Saudi-FDA.

(1)International Coalition of Medicines Regulatory Authorities (ICMRA) Covid-19 Working Group: Remote GCP and GMP Regulatory oversight inspections. Reflections on the regulatory experience of remote approaches to GCP and GMP regulatory oversight during the COVID-19 Pandemic