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Roundtable: Accelerating the path towards sustainable, future-proofed QC

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EPM editor, Rebekah Jordan spoke with Katrin Pauls (Lonza), Mark Hilhorst (Jekson Vision), and Christoph Jansen (Mettler Toledo), to discuss the factors and challenges associated with the pharma industry's move towards sustainable, future-proofed QC lab testing - including digitalisation and Pharma 5.0.

Roundtable panelists:

Q. What challenges do pharma QC laboratories face on the path to sustainability?

Katrin Pauls, Lonza: First and foremost, it’s worth highlighting that many pharmaceutical companies are now working towards a set of defined sustainable development goals, which demonstrates the pharmaceutical sector’s deep commitment to building a greener industry.

Sustainable initiatives for the pharma QC lab are now calling into question some of the traditional and established pharmaceutical safety testing methods — particularly those that consume experimental animals or natural resources. Two current examples of sustainability-driven changes to such methods are the replacement of the Rabbit Pyrogen Test (RPT) with the cell-based Monocyte Activation Test (MAT), and the replacement of traditional bacterial endotoxin testing (which relies on amoebocytes from horseshoe crabs) with recombinant protein-based methods. Such tests are a leap forward when it comes to reducing laboratories’ reliance on experimental animals and protecting natural resources.  

While these sustainable product safety tests are technically straightforward to conduct, implementing them can be challenging for QC labs. The main difficulties stem from the regulated environment in which QC labs operate. Any changes affecting the manufacture or safety of a drug product must be sufficiently validated and documented. Labs may also need to notify the relevant regulatory bodies. Since compendia across the globe are not yet harmonised, companies are often hesitant to spend time and budget on such methods.

Christoph Jansen, MT: Pharma QC cGMP labs must follow validated procedures. Changing procedures is always associated with cost and effort. Therefore, the pharma industries are typically conservative due to the resource commitments associated with changes.

For some years, regulators are encouraging the pharma industries to digitalise and move to electronic recordkeeping. Not necessarily for sustainability reasons in the sense of saving resources as the major driver, but as a good side effect.

Recently, large pharma companies have made large investments in the architecture and infrastructure of their laboratories. They are optimising heating and avoidance of waste, using rainwater, passive heating, PV solar panels, and heat exchangers. This is what Mettler Toledo, as an instrument supplier, has also done in our offices, production areas, and application labs.

Beyond these investments, achieving sustainability within analytical procedures is a challenge for the pharmaceutical industry, as they depend on offerings from their suppliers for instruments and consumables. Consequently, we see more and more that procurement departments have a focus on sustainability to try and influence suppliers to develop and offer more sustainable instruments and consumables.

Q. Could you tell us a bit more about the incentives of Pharma 5.0 – and why more pharma companies are turning to it?

Katrin Pauls, Lonza: Moving pharma into Industry 5.0 complements the Industry/pharma 4.0 paradigm (the vision of industry growth based on enhanced digitalisation, big data, and artificial intelligence), to a vision that also considers the environment, society, and the economy equally — alongside efficiency and productivity.

At its core, Industry 5.0 attempts to capture the value of new technologies, research, and innovation to drive a more sustainable industry and resilient supply chains, while respecting Earth’s resources and the wellbeing of workers.

Applying this concept to the pharma QC lab brings sustainable product safety testing methods to existing automation and digitalisation programs. In the past, QC test labs tended to work in silos, concentrating only on the production lines they control. To most improve efficiency, the duplication of activities at different sites of the same company can be avoided by focusing on Industry 4.0, enhancing digitalisation and the global exchange of data. By introducing Industry 5.0, new sustainable test methods may be validated in one centre of excellence and transferred to other QC testing laboratories at different locations. This will ultimately reduce personnel workload, project costs, and time.

Mark Hilhorst, JV: I am of the opinion that pharma is just into Industry 4.0. OEE tooling is the key to being more efficient and therefore more sustainable. Companies need high quality, reliable sorting solutions to avoid bottlenecks in the manufacturing process.

Christoph Jansen, MT: Not long ago, we started counting the various industrial revolutions. One to four were technical revolutions only: 1.0 mechanisation, 2.0 electrification, 3.0 first automation, and 4.0 sophisticated automation with internet-connected “smart” devices. Focus on digital transformation was part of this. While 4.0 isn’t completed, a cluster of big pharma companies has already started talking about “Pharma 5.0”. This takes the principle of “Factory 4.0” and adds on sustainability and the requirement to ensure the needs of the employee are incorporated.

Special benefits for pharma industries I mainly see with going electronic with the data. Next to the fact that regulators are encouraging it and that it mitigates compliance risks, there are some significant business benefits: Each “second person review” has a lot less to do and can be used for other tasks that add more value. The batch release process is much faster, and thus it has an amazing impact on the company’s cash flow. And this only touches the business benefits.

To satisfy employees’ needs, instrument manufacturers can improve their routine work through good automation and facilitated usability. In addition, good automation may minimise direct exposure to hazardous chemicals and waiting times with insufficient productivity.

One of the topics in Industry 4.0 is “lot size 1”. Automated processes produce customised items in small lots at the production cost of mass production. To transfer this to the pharma world, we speak of personalised medicine, and I have seen discussions where this was also associated with Pharma 5.0. Whatever index you use, I am convinced that this is only affordable with a high degree of automation and digitalisation.

Q. How do you think digitalisation and automation will transform quality control in pharma labs – and are there any barriers to them?

Katrin Pauls, Lonza: It’s important to note that, whatever the division or industry, digitalisation and automation do not alter the steps necessary to create products and ensure their safety. Even so, the benefits for pharma QC labs are substantial. Such advances save hands-on time, reduce human error, ease process control and documentation, and streamline results review. If errors do occur, labs can also better identify and rectify them. Moreover, digitalisation and automation greatly improve adherence to data integrity requirements, and streamlined documentation also makes reporting to relevant authorities easier.

Currently, the main barriers to the adoption of automation and digitalisation seem to be resource constraints — namely having sufficient personnel time to justify the necessary capital expenditure, as well as evaluate and establish new programs.  

Amanda Hsu

Mark Hilhorst, JV: Yes, innovation is transforming quality control. OEE and full tracking of product through the supply chain will make it more visible and production more efficient. Serialisation data with the Jekson tool can be set-up for any production line. Our single line sorter is an automated system for sorting and rejecting inferior pharmaceutical and nutraceutical products from a production line.

Christoph Jansen, MT: Digitalisation and electronic records are probably the topics with the highest relevance for the pharmaceutical industry. An indicator of this is the number of FDA warning letters, where data integrity issues and poor records management are cited. The number of citations has increased in recent years, and this should be a concern. Warning letters can be a great risk to the pharma companies’ reputation, noncompliance, costs are huge, and the risk of losing qualified lab staff at all management levels involved in the noncompliance issue.  FDA remediation guidance goes as far as recommending termination of employment for involved individuals. 

My recommendation to the pharma companies is to approach a digitalisation project by making a business case that contains the why (savings, process improvements) and how. Seek guidance (GAMP 5 Second Edition or USP〈1058 〉) and develop a digitalisation strategy with common workflows for Computerised System Validation (CSV). Start with mapping and redesigning your processes to eliminate paper and spreadsheets. Write a User Requirement Specification (URS), select a solution, and implement it. Train people early enough in the process so they understand what they are deciding for. Use the services of your suppliers, because they know their products and processes best and will save you time and effort. There are lean ways to do all this by using risk-based approaches as described in guidance documents.

Q. What assays and technologies do you think would facilitate future proofing QC testing in a sustainable way?

Katrin Pauls, Lonza: QC testing labs have already discovered the future-proofing and sustainability-enhancing benefits of automated assays, particularly with flexible, automated endotoxin detection platforms and software-based solutions for documenting results.

Looking to the future, the broader adoption of sustainable testing methods, such as the rabbit-free MAT for pyrogens and the recombinant Factor C (rFC) assays for endotoxin detection by compendia and authorities will be paramount for accelerating QC labs’ path to sustainability.

Combining sustainable solutions such as the rFC assay with robotic automation may be important for further QC transformation. Manufacturers of test methods could support this adoption by developing automation-compatible packaging — for example, appropriate vialing with barcode reading capabilities. Companies could also encourage more rapid adoption of new technologies and processes with robust training and support programs, which can also be enhanced by using artificial intelligence.

However, realising the next generation of transformations may hinge on overcoming several challenges, namely the ongoing shortage and turnover of qualified personnel; training on different analytical methods, instruments and software; and staying current on regulatory requirements while also keeping up with daily hands-on duties.

Mark Hilhorst, JV: QC testing not directly, more OEE. It is not unreasonable to expect an accurate and reliable inspection system to weed out flawed items. Major pharmaceutical companies across the globe are already using vision detection and traceability solutions which are ideal for production lines of blister packs or bottles, and are designed to comply with all international quality standards.

Christoph Jansen, MT: Instruments and consumables can only be improved by the suppliers. This might take time. Selection criteria, such as the carbon footprint of the supplier’s manufacturing or their environmental agenda could be easy to achieve. See if they have projects and an agenda to save resources, such as packaging material, etc.

Instruments with a small footprint definitely help for a denser usage of the lab. These not only save expensive bench space, but also heating costs due to ventilation (fume hoods) as the same lab space is used by more instruments and applications.

Preventive maintenance is also important to extend an instrument’s service life. Instruments inherently come with a “grey energy”, the seemingly invisible energy in their manufacture. The longer an instrument is used, the better we can absorb this grey energy. However, one must be careful and stay up to date-with technology. Aged instruments may no longer be state-of-the-art and may violate the “c” in cGMP, which stands for “current” and is part of the legal requirements.

Q. Do you see a Quality Management System (QMS) as a sustainable solution in pharma testing and quality control, and are there any issues of incorporating one?

Katrin Pauls, Lonza: First, the implementation of a Quality Management System (QMS) is a regulatory requirement. QMS facilitate the efficiency of quality control by ensuring sufficient and appropriate documentation from research through the manufacture of QC test methods and results. With enhanced digitalisation, paper-based reviews and risk analysis can be dramatically reduced. Moreover, increasing automation of standard QC tests may reduce the number of repeat tests. So, from this perspective, advancing automation and digitalisation as part of the QMS enhances sustainability through improved efficiencies.

When it comes to implementing or improving a QMS, the main challenges arise from the need to maintain training and operating procedures, and from resource constraints encountered when automating and digitalising existing paper-based systems. 

Mark Hilhorst, JV: Pharma works with GMP more than ISO.  Vision machines can absorb the tiniest details of a product’s make up – the perfect size, shape, colour, and any markings. The system also uses AI learning to further improve recognition of the correct, versus the reject product, speeding up the process as the throughput increases.

Christoph Jansen, MT: For pharma quality control (QC) records, patient safety has the highest priority – even higher than sustainability. The regulators believe that this requires true quality control according to the procedures used before testing the medicine in clinical trials.

Quality control needs scientifically sound procedures and “fit for purpose” instruments.

As a supplier of lab instruments, we have a QMS to maintain the quality of our instrument production and software development. When pharma companies validate their processes in a computerised system validation (CSV), we recommend utilising our QMS. This may save you lots of time, cost, and effort. You may want to challenge us, but we are prepared for that.

Q. What regulations are evolving to facilitate sustainable analytical testing procedures?

Katrin Pauls, Lonza: Changes in regulations often follow a regional political transformation. The transition towards a more sustainable society is certainly a global effort, but priorities and initiatives differ by region.

Currently, regulatory bodies globally are working on multi-year programs to facilitate the implementation of sustainable methods within pharma companies. For the pharma QC lab, the European Commission’s activities around pyrogen testing are a good example: the current program aims to put an end to the RPT (along with other animal-based tests), replacing it with a new general chapter on pyrogenicity and removing it from the European Pharmacopeia by 2026. The European Pharmacopeia will update and revise references in general chapters and substance monographs to accommodate sustainable safety testing methods, as well as give guidance for their use. As a result, pharmaceutical companies are now strongly encouraged to implement such compendial changes for newly developed drug products.

Despite the progress and promise of these developments, global compendia harmonisation is still needed to streamline the market authorisation requests of global pharma companies. Other regulatory bodies, such as the United States Pharmacopeia, have not yet instituted a similar program to remove the RPT. And a historical review shows it can take many years to go from analytical method innovation to harmonisation. Such a long timeline for change is a key barrier for the pharma industry as it looks to evolve and become more sustainable in QC testing.

Mark Hilhorst, JV: Again, GMP sets the standard. To meet the stringent regulations in the pharmaceuticals industry, it is essential to ensure your product is right first time, every time. To help improve patient safety, and avoid triggering fines and delays, the latest automated high-throughput screening solutions for sorting and rejecting inferior pharmaceutical and nutraceutical items are a hygienic and proven method as well as 100% accurate.

Christoph Jansen, MT: The only regulation that comes to my mind is 21 CFR Part 11 and the equivalents in other regional regulations. This regulates electronic records as part of the digital transformation. Guidance documents, such as GAMP 5 Second Edition or USP 〈1058 〉 help interpret it.

In my view, one of the sustainable aspects of electronic records is the absence of physical paper. I think paper records are an amazing waste of resources and time. The storage is expensive, and data retrieval is a nightmare already after six months, but the storage retention obligation can go up to 50 years, depending on the nature of the data.

Q. What do you think still needs to be done to future proof QC testing in pharma?

Katrin Pauls, Lonza: Moving towards sustainable, future-proofed QC testing requires several changes, both beyond and within the QC testing lab.

Considering factors outside of the lab, it’s clear we need a quicker process to harmonise the global regulatory framework. This would allow pharma companies to implement harmonised testing programs across sites, regions, and products more rapidly. Often, comparison studies are set up by regulatory bodies to evaluate innovative solutions — a process that is necessary for guidelines to change — but this is typically done only at a country level. Better sharing of data, including from product validations, across different regional regulatory authorities, may help here, and would ultimately ease the adoption of new methods by QC testing labs around the globe.

Better and more frequent communication between regulatory agencies and manufacturers of testing products, particularly regarding data, results, trends, and testing needs, might also speed the development and adoption of new technologies.

Several actions at the lab level could also facilitate future-proofed QC testing. These include harmonisation of methods, training, and procedures across sites; implementing company-wide cross-functional teams to evaluate, report on, and establish new methods; and securing secondary suppliers to safeguard against supply disruptions.

Ultimately, no one can accurately predict the future. Labs should remain vigilant and continually evaluate new technologies and ideas, all while maintaining efficient current business operations. With this approach, labs can more effectively shield themselves against unanticipated disruptions. 

Mark Hilhorst, JV: Keeping up with drug development for an ageing population and new diseases is challenging for the pharma industry. It is essential that the billions of tablets rolling off UK production lines are in perfect condition – one bad shipment could potentially spell disaster both financially and to reputation. Digitalisation, documentation, serialisation data and full supply chain tracking of the products will improve patient safety.

Christoph Jansen, MT: In short: Digitalisation. In surveys we have made, it seems that 80 percent of the pharma companies still do not give those projects enough priority, and it is improving only slowly.

I think lab design is another rather easy way to accomplish sustainability. But here, I can only speak as a customer myself.

Rough estimates from 2014 calculated the annual plastic waste in laboratories to be 5.5 million tons globally, which would be 1.8 percent of the total global plastic waste. These are mainly consumables. Reducing this amount should be a target. Well, this is more difficult than it might sound. Especially in life science applications that need single-use reactors and consumables, such as pipette tips. Do not replace them with technology that potentially is much more critical with a higher environmental burden (cleaning and cleaning validation). In my view, this needs a lot of rethinking of processes and will take time. Our company has started projects already which have this in focus, and some improvements are already on the market.

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