GMP and Digitalization: Some Basic Thoughts

It is almost 8.00 am, we are standing on front of a building which houses an officially GMP-accredited contract laboratory service. Our task for today: carry out a full blown GMP-audit on the contract lab.

On the inside I am a bit excited, because I know that in each audit I do not only evaluate others, but I will also gain and learn! And each auditee - be it a laboratory, a GMP-manufacturer or a material supplier (API, excipients, packaging materials) is different, and each uses different ways and systems to implement GMP. So far so good.

Later that day the audit is over and my co-auditor and I we feel overall happy with the audit. Still - we also feel disillusioned: we had expected a more modern way of raw data, data and document management. What did we find? An almost 100% paper-based GMP- and data management system, with all its nicks and dents when it comes to the GMP such a system can provide - it is alright, but it no doubt has limits.

Fully paper-based - that something like this still exists? And that in a GMP-bound establishment? It sure does still exist.

In the GMP-Universe the Digitization Truck has departed, but by far not delivered to all yet!

In our line of work at Experts Institut we are time and again surprised as to how many companies in the drug manufacturing, medical device and cosmetic GMP area operate with a very low degree of digitalization of processes and data management. It grounds everyone I believe and alerts us to the reality that digitization is by far not as advanced in the regulated industry as we might want to make ourselved believe or think - as much as it is a socio-economical and political desire among regulators and industry. In fact though, it is not(!) a given, it is not a self-propagating realization all over the place. And this does not only concern small companies who seem to just not be able to finance the digital transformation. It also concerns for example medium-size GxP-entities. If You think that the size of a company is an indicator for its degree of digitalization then You need to think again. There is no such connection. You′d be surprised what we encounter in our daily work.

Even politics, cultural Western optimism and the strong drive to achieve and constantly change toward something new is not always the recipe for producing a digital revolution by and large.

Incentives for change must come from the market, it must be attractive, plausible to implement and at reasonable cost. And in a highly regulated area like the white industry (Pharmaceutical GMP, Medical Device Quality Assurance, Cosmetic-Industry) New means not only Opportunity, but also Risk. And in white industry products the Risk is considerable. An excellent example is the timidity of the GxP-industry to enter continuous manufacturing transformation - for a lack of experience with the regulators in this area. A similar reason may be at the root of the spotty coverage of digitalization.

Concerns and Opportunities of Digitalization for GxP Establishments

Some companies shy away from larger transformations due to finances thin-stretched, and due to a blurred understanding where then the actual benefit of digital data- and process-management really hit home positively.

Others simply do not see any need to change and keep up with modernization because for a period of time resisting change can go without noticing any consequences in the business numbers and balances. Even in terms of basic GMP-systems quite a few companies are chronically underfinanced.

Again others are apprehensive about the risk that may come to their data and company information due to migrating eveything into electronic formats, networks and clouds - and that is a very understandable risk. There are solutions to protect data from even the most sphisticated attacks, but they will cost.

Looking at the opportunities: once digitalization has reached a company′s operative processes - where product is actually made (not just where warehousing and document management are electronic) - a company has arrived on a temporary plateau of readiness for tomorrow.

And here is the thing: that readiness will likely make or break any business eventually - but most certainly a GMP-business!

You will need digitalized company processes (manufacturing, analytics, logistics, quality management, compliance, engineering and technical systems) and data management to be ready for:

• a globalized approach in making business wich data, knowledge and information sharing at the top (regulatory submission, block chain approaches for decentralized data management),
• adapting to constantly advancing regulatory standards for GMP-data management and managing modern technologies in development and even in routine production (see for examples EU GMP Guide Annex 1),
• the time when advanced and continuous manufacturing becomes more and more established (and this is already happening),
• advancing cost efficiency concerning staff Your system would otherwise require to cater to the massive burden of GMP-/GxP-requirements.

Where to start? And how to get on the Truck?

Digitalization in a GMP-/ GxP-liable company typically follows some sort of evolutionary model.

1. Basic for any company is to have at least material management systems, warehousing and logistics managed by electronic systems. At least for article data and inventory as well as location and status management such systems are standard. This is nothing new of course. But I tell You: there are in fact some companies that don′t have even that.
2. The second layer often is electronic Document Management (eDMS).
3. Then comes electronic batch record - at least partially, more often electronic deviation and change management or other QM subsystems - mostly non-integrated but separate applications.
4. and then - typically - a full electronic Quality Management System, some commpanies using the opportunitydigitizing their business and administrative processes if they haven′t so yet.
5. Global companies need to deal with additional issues with data sharing and data security across the corporation, leading to for example decentralized data storage solutions for example controlled via block chain technology.
6. And by the latest at that point comes the phase of trying to integrate all of this.

As You can see: if Your company is currently a low-digitized business - do not be dismayed - You may have just about missed out all those years where all the others have hustled and bustled to add one little digital island system after the other. And You now have the advantage to look back on this and make a decision to roll out digitalization compreheneively and for the first time!

Digitalization in a GMP-Environment

There are challenges of course. Digitalization cannot be rushed or it will result in a gigantic failure with data loss, loss of company spirit and - worst case - of good people who will quit over the frustration of the failed digitalization effort. Leadership will lose credibility and trust - which is worse than anything from a company perspective.

The more integrated You advance Your digitalization the more keeping in with the validated state is a true GMP-challenge. And a huge caveat I must place here is: Be very thorough when working with validation-packages from software suppliers! They come from a non-GMP quality system environment - often no QMS around the software development at all - and so You need to take charge of what is done concerning validation (initial, updates, integration and post-integration management) - even and especially when it is an ISPE GAMP?5 category 3 or category 4 system. And do not mistake brand names for assurance of GMP-compliance. Our audit practice shows that even systems which ar heavily advertized for can lack basic regulatory compliance requirements or are not fully compatible with local national GxP-requirements (an issue that even electronic deviation workflows or eBR systems can have).

For some newer technologies (Blockchain Technology, Decentralized Data Management, AI / Machine Learning / Neuronal Networks) You must understand: regulatory agencies are yet to say and to judge what they require from the GxP-viewpoint, depending on each situation of digital integrated process landscaping and data generation and management. Of course You can apply the current GxP-regulations′ point to now - but it may not in all cases be what You need.

And take a good look where You will market Your products: some regulatory agencies are on high alert concerning data and processes in digitalized environments and close to publishing guidance, others are - yet - fast asleep but won′t be forever.

What We (EI) do when We support a company in digitalization or digital transformation?

We Support Your planning - Organization and Required Efforts:

• Feasibility study, digitalization concept, regularoy GMP-/GxP- and cGMP compliance assessment, also of existing levels of digitalization.

We prepare Your body of documents:

• With You we estalish and review the required GxP-relevant document You will need for individual systems and for global structure concept papers and policies keeping in with Your data integrity and data security requirements.

We work with those from Your company who will live and operate the / in the system:

• Coordinating a digitalization project can be challenging and requires a sober and coordinative mind and management skills. Often companies new in the arena of digitalization do not have personnel to carry such a project and coordinate all the stakeholders - on top of their daily workload. But we (EI) have people who can take such a mandate and help Your own people advance in knowledge and with the project alike.
• We keep alliance with partners who can drive the actual digitalization of data, especially if You find no suitable business counterpart for example doing power BI for data pooling structures and more.

What will it take Your company (with or without external help)?

If You do digitalization - especially if You take a larger step (no matter in what area in Your GMP-, GDP, or GxP-company), You might as well do it wholeheartedly.

• It will take extra effort on the part of everyone involved, and this is a real extra - not just an imaginary thought. Prepare Your staff wisely! Communicate with credibility where this is going.
• It will take a darn good project manager and project management structure that can react to the unforeseen.
• It will take nerve - lots of nerve - to face how many things that used to be non-digitalized actually never really worked! This will cause delay.
• It will take plausible timelines that are only to a limited degree tied to immediate business goals - for then if it (digitalization) delays or fails - then all fails!
• And - most importnatly - it will take a change agent to generate acceptance of the things that are coming.

All things considered: be courageous and give it a go. In the long run there will likely be no way around a rather comprehensive digitalization for GxP-companies. Now is a good time.