In this blog series, we’ll be exploring the concept of a Unified Knowledge Space, how it fits into Pharmaceutical Manufacturing, how you can implement it and its benefits.
In our first blog series entry, we explored the general concept behind the Universal Knowledge Space (UKS), uncovering its defining characteristics, when it might be needed and examples of how it's become critical for other industries such as construction.
Now, in this next installment, we’ll delve into the challenges confronting Pharma manufacturing, how the traits of the industry fit with the concept and specifics of what it could look like.
Challenges in Pharma Now
At Blynksolve, we spent a lot of 2022 dedicated to speaking with professionals working in Pharma Manufacturing. This involved interviewing a wide variety of functional groups including Operations, Quality, Engineering, Tech Transfer, Automation, Safety, etc. and at various levels in their organisations. After 100 interviews asking open ended and non-leading questions, some very clear trends emerged.
Timeline Compression. Interviewees reported that, Covid aside, the expected time to bring a drug from candidate to market is getting tighter. This is primarily driven by heightened competition in the industry which can be seen in the popularity of partnering with CDMOs which have the expertise and facilities to get products to market faster. Speed to market is a key business driver for pharma to get ahead of other potential products which may become far more difficult and expensive to displace once in market. The period in which products are under patent is when pharma companies bring in the most significant and defensible revenue in order to cover all the other myriad of costs associated with bringing a drug from inception to patient.
Higher Expectations. The steady updates to regulatory requirements and best practices have resulted in higher expectations for manufactures. Changes such as the relatively recent focus on data integrity has added to the required control, with big pharma being under the greatest scrutiny to have their compliance air-tight. Regulators are also looking for wider use of innovative technologies to improve control of manufacturing.
Higher Complexity. As more sophisticated products are developed, so too are the processes used to manufacture them. In order to improve quality, consistency and yield, processes have been intensified with a greater number of steps, especially for biologics. On top of this, new digital technologies such as MES and automation have also become more common to improve speed and control. That said, these new technologies add further layers of complexity that require greater levels of cross functional coordination. between more specialised functional groups. Ensuring effective communication and alignment can be a challenge, demanding more time and effort compared to the old manual or paper based approach.
More Movement. More recent work habits have seen employees jumping from roles and companies more frequently, especially for those in the early parts of their careers. Spending an entire working life in one company is seen as unusual, especially with so many opportunities currently in the industry. Though companies try to incentivise staying, the reality is that for many people, moving regularly offers various benefits, exposure to new work cultures, chance to work on something different, ability to move up faster in growing organisations and bolster earning power with all this varied experience. This new norm means that those experts who stay in a single company for decades have become quite rare. Consequently, levels of knowledge on specific manufacturing processes and facilities are struggling to be maintained over time with the steady flux of people.
Limited Tools. Another trend was an overall sense that ways of working aren’t keeping up with expectations. With all those other changes impacting the industry, there hasn’t been sufficient changes to methodologies or systems to absorb the higher workload. Some systems such as MES or paperless validation systems such as Kneat have boosted productivity in their respective areas, but there are still areas where too much time is being spent on low value-add activities using frustrating and outdated systems.
Common Burnout. With all the other factors outlined above, those working in Pharma manufacturing are under more pressure than ever. The expectation to deliver more with less people, less knowledge and less time, all with the same tools and methods has led to increasing employee burnout. We recently ran a Linkedin Poll which asked the question “How much of a problem is burnout in pharmaceutical manufacturing projects?”. Of the 60 responses, 47% believed burnout was a severe problem, 48% a moderate problem and only 5% believed it was a slight or non-problem. These findings coincided with our interviews, whereby 76% of interviewees raised the subject of burnout and increased work related stress.
Characteristics of Pharma
In the last blog, we outlined when a Unified Knowledge Space might be needed. Let’s examine the traits of Pharma manufacturing against these criteria.
The overall deliverable requires many distinct functional groups to collaborate and coordinate
This is undoubtedly true for Pharma manufacturing. The vast majority of aspects require alignment between all the various groups, such as Operations, Quality, Process, Engineering, Automation, Validation, etc. Each of these groups have unique overall deliverables and distinct perspectives on the whole picture. Check!
Decisions and details are heavily interdependent on each other
Tied to the previous point, more often than not, decisions require alignment between all those functional groups to ensure that decisions fit with all the various deliverables. As much as any group would like, one group can’t just run off in their own direction without risking misalignments and overlooked mistakes. Check!
Work results in creation of large amounts of data in many different formats
This includes designs, test executions, procedures, registers, forms, supporting documents, all presented across various formats such Word docs, PDFs, Excels, drawings, diagrams, slide decks, databases and paper folders. Massive quantities of each are created for every manufacturing facility across many repositories. Documentation in fine detail is a core part of GMP. The mantra of “if it isn’t documented, it didn’t happen” is one of the first things anyone is told when they join the industry for a reason, resulting in lots of documentation. Check!
Overall deliverable is cognitively complex to understand clearly
If we’re considering the manufacturing process and the controls around it as the deliverable, it’s safe to say that this is not an easy thing to see and understand clearly. This is mostly due to how many layers there are. You have the Equipment layer (P&IDs, GAs, Specs, calibration), Operations layer (Batch records, SOPs, Material management, training ), Process layer (Process Description, critical parameters, samples plans, process and cleaning validation strategies), Automation layer (systems, software functional designs, alarms, reporting), Quality layer (Quality Risk assessments, compliance), Safety layer (HAZOPs, Risk Assessments) to name a few.
As all above are interconnected, being able to see how all the layers interact with one another is an incredibly time intensive thing to do and unfortunately time is a resource which is hard to come by in Pharma manufacturing. Added to this, when getting manufacturing up and running, all these layers are constantly changing in parallel with one another so seeing a clear picture of how it all fits is almost impossible with current methods. Check!
Context and meaning of knowledge is required to endure into future
All these various layers of information, knowledge and decisions need to be traceable and understood throughout their lifecycle, from cradle to grave. It doesn’t matter when a regulatory inspector comes knocking, their questions can go as far back into the facility's history as they’d like. A solid knowledge basis which includes context is needed for every investigation. This includes change control, improvement and inspection, otherwise original meaning is lost, elevating risk of errors or regulatory findings. Check!
With the combination of each of the items above, there’s a clear need for a UKS in Pharma manufacturing.
What does a UKS look like for Pharma Manufacturing?
It’s not a case of taking what works as a UKS for another industry and directly porting over. An application of the concept for Pharma has to be done with the specific understanding of how knowledge flows, how it’s created, how it’s used and the nuanced requirements.
The key question in determining what a UKS should look like in a given application is what is the deliverable? Calling back to part 1 of the blog, let’s look at construction and ask what is the deliverable there? Why, it’s the final building of course! Ok, let’s deconstruct this, pun intended.
You have just been brought to a brand new shiny building and it’s all yours. They’re about to handover the keys but before they do, you ask a few questions. To what standards was it built? What materials were used? From what supplier? What maintenance is required? What are the key structural components? Where are the electrics? How deep are the foundations? The person about to give you the keys asks you to trust that it’s all up to code and that all the documentation is in there, somewhere. Hmm. Clearly the physical building is just one part of the overall deliverable for any major construction project.
Other considerations, as with everything else in life, are cost and time. So with all those in mind, what does the UKS look like? It would have a dynamic digital representation of the building, be able to store all required information and allow collaboration in a shared space. This is exactly what Building Information Modelling (BIM) is.
So what about Pharma manufacturing? The obvious deliverable is the physical manufactured product, similar to the building analogy. Beyond this, other deliverables are that the product is of the required quality and efficacy at the lowest cost.
This is the end result which needs to be proven through documentation, validation, processes, procedures and systems demonstrated to be in a state of control. Creation of these is the bulk of the work required to achieve this desired result and so is where a UKS would give the greatest benefit. A UKS for Pharma manufacturing would therefore be a digital representation of the process where documentation, procedures and systems can be layered on top of the process and where collaboration and decisions can be facilitated.
Blynksolve's UKS Approach in Drug Substance Production
There are many ways that a UKS could be formulated for a given purpose. At Blynksolve, we’ve focused on Drug Substance Production where our UKS is a hybrid of a P&ID, HMI, SU Diagram and various user defined data layers. These data layers can cover everything from Parameters, Samples, Docs, Materials, Automation, Training, etc to accelerate the output of those typical documents and plans produced. Once a manufacturing process has been created as a Digital Knowledge Twin, it’s like having a clear map to navigate all those layers. Anyone can go to any point in the process and quickly understand what’s happening and all important elements. The intent is to not displace any existing systems, but instead to complement those typically used in Pharma.
Regardless of the form that a UKS comes in, the philosophy behind it should remain approximately the same.
It’s for many distinct functional groups, not just a single group. There are enough tools in Pharma manufacturing for single functional groups which help them to carry out their work. A UKS on the other hand shouldn’t give preference to a group, but instead focus on the overall deliverable and work backwards to all the various groups which must contribute.
The depth of detail required should be balanced to be maximally useful to the most number of people using it. There is a possibility to dive down into fine detail if required. Do other groups need to know the fine details of how the automation is structured? Do the likes of Operations need to know the equipment material specification? Probably not. If all information is weighted and presented equally, this could lead to users being overwhelmed by the amount of information and critical information could be missed. The key questions when deciding whether or not to include information are; will this information benefit other functional groups to do their work, gain a better holistic understanding and make informed decisions? If you can’t definitely say that it would, then leave it as an additional resource for those who want to dig into the detail rather than being placed front and centre.
It is a living knowledge source and not a point-in-time activity which benefits both immediately and far into the future. The ideal UKS in Pharma should be there from day 1 to day 10,000 and beyond. It should act as the most efficient way of facilitating decisions on fundamental design, improvements and investigations and a way of avoiding duplication of work.
It’s an agreed and shared understanding. Its accuracy is trusted at any given time. This is critically important. If the accuracy of a UKS lapses and falls significantly out of alignment with the current state, trust will be lost and efficiency of use is diminished with people spending more time searching for and confirming information. In Pharma, a clear source of truth is critical for avoiding mistakes, confusion and inspection findings. Access control and change traceability also reinforces this to avoid unintended changes that can’t be undone.
It is a space where cross-functional collaboration on designs and decisions can happen in real time and where the outcomes can be captured immediately in the flow of work. This again feeds into the efficiency aspect. If you have a system which must be laboriously updated after design meetings, then this negates potential time savings. In addition, being able to collaborate, create and present a shared understanding in real time with all stakeholders will result in reduced risk of errors or miscommunications.
It is highly visual, has an intuitive interface, is easy to access and to understand. It can be handed to someone just in the door who should be able to navigate and understand without overbearing training. It is designed around how people best navigate, understand and create knowledge. This is fairly self evident, if you have a system which is difficult to understand or interact with, then likelihood of regular use goes down significantly. People shouldn’t be afraid to jump in, look around and create rough drafts in a personal sandbox to get used to the system.
Though the industry is facing challenges on many fronts, a Unified Knowledge Space offers a way for Pharma manufacturers to improve productivity, control and output while not fundamentally changing the way of working. As demonstrated by the analysis above, the specific traits of Pharma manufacturing are well suited to the concept. As shown from its application in Construction, a Unified Knowledge Space can be transformative for efficiency, quality and output of organisations. That said, they do require understanding in order to identify if they are appropriate and how best to use them.
In the next blog installments, we’ll examine how various use cases and applications can benefit from a UKS.