+390677209020 | +39 0267380552 info@direnzo.biz | sedemilano@direnzo.biz


GMP validity extension, Distant Assessment and on site audits: AIFA inspection unit slowly back to normal

Audits at medicines and APIs manufacturing sites are certainly one of the pharmaceutical manufacturing activities that were more affected by the Covid 19 pandemic.

Travel restrictions, the need of social distancing and inspectors’ safety protection have made the performance of any type of inspection practically impossible, for routine inspections as well as under extraordinary circumstances (activations or changes of authorised manufacturing sites).

Such conditions, shared at international level, have forced AIFA to take action on two fronts: from one side, they supported the extension of the validity of GMP certificates at the GMP/GDP Inspector Working Group; on the other, they adopted a series of remote activities in order to avoid a block of the GMP compliance controlling activities.

The validity of the GMP certificates was first extended until the end of 2020, then to 2021. It has just been confirmed that the extension is valid throughout 2022.

With the pandemic still raging, having suspended the planning of any routine on site audits, the GMPAPI and GMPMed units have decided to focus their efforts and inspectors on activities targeting the activation of new sites and the extension for new substances or manufacturing lines, adopting a Distant Assessment system.

According to the EMA definition this is an “assessment of the compliance of a site with the Union GMP/GDP principles performed by officials of Union Competent Authorities on the basis of documents and interviews and supported by technology for communicating, accessing systems, sharing and reviewing documents and other information, without the inspectors being physically present at the sites where the activities subject to the assessment have taken place and where the inspection would ordinarily be hosted” (ref. GMP/GDP Distant Assessment Guidance, 15 October 2020).

As of March 2020, the sole GMPAPI Unit has carried out 22 Distant Assessments, that were concluded in approx. 3 or 4 months. As Di Renzo Regulatory Affairs, we took part to some of them and had the chance to witness their progress and understand their limits and opportunities.

The planning of Distant Assessments carried out by AIFA have given priority to the control of the manufacturing of medicines and APIs intended for the treatment and prevention of Covid-19. The decision to proceed to a Distant Assessment has been defined based on a specific risk assessment that considered the criticalities of the sites, its productions, its inspection history and, finally the specific applications already submitted.

Whereas the request and assessment of pre-inspection documentation has maintained the typical audit structure, although including more details, the planning of the Distant Assessment has required the implementation of an appropriate information system.

In details, it was essential to have more reliable and efficient platforms including video conferences with stable connections and easy detection of interlocutors, quick and safe exchange of (often big-sized) documents, possibilities of breaks-out rooms and presence of smartphones or mobile video cameras allowing the direct shooting of premises, equipment and ongoing manufacturing activities. The use of pre-prep videos was rarely accepted.

In order to ensure the sustainability of the above activities, the presence and support of the IT service was strongly advised throughout the whole Distant Assessment, as well as a test session with the inspectors; moreover, it was very useful to share the site layout in advance, along with pictures and flow charts, in order to support the inspectors’ better understanding.

Compared to on-site inspections, the need to share documentation as much clear and exhaustive as possible is, in this case, even more marked. This allows assessors to carry out their remote inspection with no waste of time and/or misunderstandings.

All these precautions have enabled AIFA to authorise essential changes and activate new lines, buildings etc., without transfers and ensuring social distancing. However, some limits were detected, such as the restricted visual field of video cameras and the impossibility to listen to the personnel’s conversations.

This has induced to consider the Distant Assessment as an emergency solution, that cannot replace on-site inspections. The Agency has already found a way to schedule and carry out on-site audits to confirm decisions previously adopted based on remote inspections.

The experience collected in these two years of emergency has pointed out that, in spite of the great effort by both inspectors and manufacturing sites, Distant Assessment has shown to be limiting. In the future, the Agency does not expect this will be completely excluded in the future, however it will be considered a useful tools in less critical situations or used beside more traditional tools.

Foto di Free-Photos da Pixabay