[Stability Testing related News – vol.53]

◆  Inspectors grounded – a year of innovation (26-Mar-21 MHRA Inspectorate Blog)

Posted by:Paula Walker

As with all areas of the Agency, the start of lockdown this time last year meant a complete change to the way of working for the inspectorate, with the potential to impact dramatically on our ability to maintain regulatory oversight of public health.

Inspectors spend a huge chunk of their working time away from the office, out on a variety of sites including pre-clinical sites, manufacturing facilities, clinical trial sites, pharmaceutical company offices and medicines distribution sites. With our whole fleet of inspectors grounded, swift action in innovating the way we inspect was required.

Since the start of lockdown we have now carried out over 750 inspections conducted remotely across the Good Practice Standards (GxPs), a huge achievement given both the pandemic restrictions and also juggling with caring and childcare responsibilities, both on the part of the inspectors and those we are required to inspect. The MHRA inspectorate has maintained an international perspective on our remote inspections, sharing our experiences through the International Coalition of Medicines Regulatory Authorities (ICMRA) and Pharmaceutical Inspection Co-operation Scheme (PIC/S), including training other regulators in our approaches.

So how have we achieved this?
While we were already conducting some activities remotely pre-pandemic – such as ‘Day 1’ of the inspection involving remote data review and accessing electronic systems – most of our inspections were on site. Working as a team across the inspectorate, experiences were shared resulting in the implementation of a variety of methods to enable regulatory oversight of patient and public health and security of the global supply chain. This has included changing ways of working that we will continue to conduct post-pandemic, including desk top assessments for low risk organisations, and amending the way we operate our Inspection Action Group for critical findings to ensure that inspectors are not in a cycle of re-inspecting sites that are not yet in compliance.

Digital developments
Due to the agile approach of inspectors, and willingness to adapt quickly to the different landscape we were working in, within the first month remote inspections were taking place in all areas. A variety of file-share platforms have been used, including those already established in the companies inspected, as well as FileShare and, more recently, Teams Channels. Teams channels can now be set up for every inspection and allows sharing of large data files, as well as providing a space for inspectors to discuss inspections with the companies, replicating the inspection team being ‘in the room’ together as far as possible. This has only been possible through the amazing support from our technology services teams.

The future of inspections – innovate, innovate, innovate
So where do we see this going? One of the unexpected outcomes of remote inspections, is that they actually take longer to perform than the on-site model due to the limitations (even with technology) of not having that real time presence of questions raised and answered or being able to ‘dig around’ to see what the compliance level of a facility is really like. As Chair of the ICMRA Covid-19 working group on the Digital Transformation of Inspections, I have found the consensus view across global regulators is that working remotely is a great ‘tool’ in our inspection toolkit, but will never replace what can be achieved in person – and there are many areas that are just not suitable for remote approaches, such as sterile facilities – this is particularly relevant at the moment as we work closely across the Divisions on vaccines.

The inspectorate also performs a significant number of inspections overseas to ensure the quality and safety of medicines supplied to the UK. Despite vaccines roll-out it will be some time before we are able to return to those sites.

Moving forward, our inspectors will therefore continue to innovate, with our focus currently on incorporating ‘visual technologies’ into our toolbox, which will enable us to have some level of ‘eyes on site’ for those areas where it is critical to see the facility or clinic where the work takes place.

This provides an opportunity to break new ground in ensuring that patients and the public receive only those medicines with the quality and safety we would expect, whatever emergency situation we find ourselves in.


◆ FDA updates Q&A Guidance on Inspections and Applications (26-May-21 ECA)

After the publication of the Guidance for “Remote Interactive Evaluations“, FDA has updated its “Manufacturing, Supply Chain, and  Drug and Biological Product  Inspections During COVID-19 Public  Health Emergency Questions and Answers Guidance for Industry“, clarifying some of the plans to take when the agency cannot conduct an onsite inspection of a facility. FDA acknowledges the fact that on-site inspection activities are “limited due to factors including travel restrictions” and “intends to continue using alternative tools, when appropriate, to evaluate facilities”.

The document explains what FDA deems as “mission-critical” and how it will ensure the quality of imported products while inspections are limited.

How will limited inspection activities affect applications?
FDA states that it is “using all available tools and sources of information to support regulatory decisions on applications that include sites impacted by FDA’s ability to inspect due to COVID-19.” Examples:

  • FDA will continue the quality assessment of all applications per normal assessment operations (using a risk-based approach).
  • Additional tools will be used wherever possible (review of the compliance history, using shared information from other foreign agencies, requesting records “in advance of or in lieu of” facility inspections).
  • FDA will continue to work directly with the applicants and encourages those “to be in communication with all their facilities and sites to ensure timely responses to any inquiries”.

What if an application includes sites that cannot be inspected because of travel restrictions?
FDA will not automatically send out a complete response (CR) letter to the applicant if FDA cannot conduct an inspection. “Decisions regarding applications will be based on the totality of the information available to FDA”, this includes information obtained from use of the tools described in the Guidance. Decisions will then be made on all the available information. This can lead to the following decisions:

  • FDA plans to approve the application
  • FDA plans to issue a CR letter with facility- or site-related deficiencies
  • FDA plans to issue a CR letter without facility or site deficiencies
  • FDA generally plans to defer action (i.e., miss the goal date) on an application
  • Further details can be found in the document.

How does FDA intend to prioritize inspections as travel restrictions are eased or lifted?
A risk-based approach will be used to prioritize the inspections. This can include:

  • Impact of product availability to public health
  • Safety of the investigator
  • Location of the site and associated travel restrictions

FDA also notes that applications can still be submitted if facilities in regions that are impacted by COVID-19-related travel restrictions are included.

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