Virtual Qualification and Pharma 4.0® Thinking During Lockdown

qualification

Virtual Qualification and Pharma 4.0® Thinking During Lockdown

Virtual Qualification, how can Pharma 4.0® thinking help during Covid-19 lockdown and what lessons can we apply to virtual qualification?

The events of Covid-19 have opened up a new world of vulnerability to all industries, and especially those highly regulated like the medicinal products manufacturers and the possibility of Pharma 4.0® Virtual Qualification as a tool going forward. Sites that have managed to remain operational have done so with strict guidelines on hygiene and social distancing which means no one should be on-site unless necessary.

New capital investment projects the world over have either been delayed or scaled back while industry waits patiently for more favourable conditions and for everyone to come out of their isolation. The response from administrative and other “soft” functions has been simple, stay away from the office and if possible, work from home. Projects that require free movement of specialized personnel, resources which may not be locally available, may face substantial roadblocks with international travel restrictions.

So, the question is, assuming that only hardware and materials (and data) are able to move “freely”, how do you go about validating a major pharmaceutical project during Covid-19? Can Pharma 4.0® thinking help?

The question is mostly hypothetical at this stage as there are many other reasons why projects are delayed. But much like how the quarantine showed everyone the advantages of remote meetings through Teams, Zoom or GoToMeeting, there is something that quarantine can teach us about other aspects of industry moving into the future…in the form of Virtual Qualification.

Alternatives to Onsite Validation

Let’s look at the various stages of a project and see where advancements have already been made over traditional methods and propose alternatives to “Onsite Validation”.

The difficult questions to answer are those where the rubber meets the road so to speak. Project milestones where there appears to be no real alternative to sending a human being to site. Stages that require trained eyes on a tangible outcome are areas where we are going to have to get imaginative.

The area that has seen the greatest innovation is the concept of the Real Digital Twin (RDT) and its implications as a potential alternative to Factory Acceptance Testing (FAT) and Virtual Qualification.

FAT involves setting the equipment up at the supplier’s factory as near as possible to how it will be set up and operated at the client’s site. Critical Process Parameters (CPPs) and functions are verified, and any defects discovered will be far easier and cost-effective to fix at this stage of the project.

FATs are generally attended by critical members of production and validation staff and aim to iron out any major bugs in the design of machines before they leave the manufacturer. It is also a good opportunity to get hands-on experience with the equipment at an early stage in development for training purposes.

RDT’s mimics the process of performing FAT, but with a virtual replica. The machine is built within a computer physics engine which can entirely replicate the machine and materials with incredible accuracy and well as simulating the laws of motion and gravity, call it Virtual Operation, a nice extension of Pharma 4.0®.

It allows for setting up failure scenarios which would be far too dangerous and expensive to perform in real life and can be reset and rerun at the click of a button. The simulation can even be set up to be controlled by the same Programmable Logic Controller (PLC) equipment as will be used to run the actual machine.

While this is technology is currently being used for certain high-risk projects and in conjunction with a rigorous FAT, the execution of FAT tends to go far more smoothly than it would have without the RDT. In other words, there approaches a point where if the RDT is accurate and robust enough, then executing a FAT might be considered overkill.

It is not too much of a stretch to imagine RDT’s or virtual qualification providing enough assurance of a machines performance that it could replace the need for a FAT all together.

These kinds of simulations may even be exported and used as part of onsite training. The operator may be asked to set up and run a virtual batch and meet certain prerequisites prior to being allowed to operate the equipment.

The stretch comes in imagining a replacement for Site Acceptance Testing (SAT) and Installation Qualification (IQ). The client and the equipment supplier can arrange a subject matter expert to direct an operator on-site with a camera to aid in the required visual inspections of the site and installation. This is still missing out on aspects of IQ such as assessing the materials of construction where having an expert in the room may be invaluable. And indeed, this may be the point where the concept falls apart. This kind of IQ method may need extensive trials to ascertain with a high degree of confidence, whether it is an appropriate replacement to the traditional onsite IQ.

Once we are out of the woods of IQ, the prospect of Operational Qualification (OQ) and Performance Qualification (PQ) become a bit brighter.

Remote Control and the Internet of Things – Part of Pharma 4.0®

Most modern machines have the option of remote control, or IOT as part of the Pharma 4.0® initiative, but it is rarely utilized beyond the site monitoring software for legitimate fear of a security compromise. The OQ and PQ could absolutely be performed remotely, the testing data harvested, and a report formulated. This is provided that steps are taken to mitigate the IT security concerns of the site and there is a solid line of communication with a set of trained on-site staff to perform operations under instruction.

Systems which are isolated from the internet by design could have a temporary connection setup over a secure Virtual Private Network (VPN) for the which the technical staff can use for the duration of testing.

There are circumstances, during a large complicated project where the only way to fix an urgent programming bug is to plug a modem into the control cabinet so that the firmware can be updated by the machine manufacturer who may be on the other side of the world.

This is obviously not an ideal solution as it creates a major network security risk effectively providing a back door into the site’s secure network but the alternative would be to wait a fortnight or more for the technician to arrive on site. The system is not left connected for longer than is required and is removed from the cabinet as soon as the project goes live.

The same could be said of remote qualification in the current climate i.e. provided the benefits outweigh the risks and the practice is appropriately supported by modern technology, it may be worth considering the option and examine what Pharma 4.0® has to offer more carefully.