Are You Label Ready?

In a recent interview with our life sciences team, I asked Simon Jones, Loftware VP of Lifesciences Product Management, and Bob Bowdish, Loftware Senior Account Executive of Life Sciences, about the transformation of the clinical trial supply chain.

Q. What's happened in the last couple of years in the clinical trial sector?

Simon Jones: It's been a challenging two years with quite a lot of change - mostly driven by the pandemic which put additional demands on the industry. As a result, the clinical trial industry pulled together in response to the need to produce vaccinations and support clinical trials that were already underway, where patient safety remained critical during periods of lockdown.    

However, it’s not just Covid-19 that has caused challenges over the last couple of years. Another catalyst for the change has been the significant uptake in biologics trials, in terms of volume and geographical reach. The accompanying cost to manufacture clinical trial medication and source comparators may require changes to traditional supply models.    

Another thing that our customers have found challenging is continuing regulatory changes. Of which the most significant has been the introduction of EU clinical trial regulations which has influenced how clinical trial supplies are being handled.   

Bob Bowdish: Covid showed us what is possible in terms of shorter clinical development timelines. Sponsors are choosing service providers that can help them reduce the number of parties involved in the trial process. CDMOs are responding by adding additional service lines.    

Q. How has the industry responded to these challenges?

Simon Jones: It's been tough, but the industry has performed very well thanks to a significant level of collaboration between pharma sponsors and their service provider partners, and I think the changes that we see here have also had an impact on how packaging and labeling have been performed.   

The drive to perform Covid vaccination trials quickly led to a step-change in terms of the need for trials to be faster and more adaptable. The last couple of years have seen a big change in the growth of adaptive clinical trials and industry initiatives like decentralized clinical trials have come into their own.    

Additionally, it was clear that sponsors both collaborated more and relied upon their service provider partners more than ever before. As a result, we're now seeing a level of transformation amongst those service providers where they are looking to standardize or operationalize some specific supply chain initiatives that they may have put in, in response to the pandemic and which they now want to keep.    

Bob Bowdish: Covid, lockdowns and patient safety concerns put existing clinical trials at risk. Sponsors began leveraging service providers to utilize direct-to-patient supply for the first time. One large biologic sponsor literally picked up the phone and called shipping companies that could come to pick up kits and take them to patients’ homes. Another rare disease sponsor had only one patient in a country and had to make arrangements to get kits to them. Also, supply chain issues such as shortages with glass vials or sourcing comparators required sponsors to reach out to service providers that they had not worked with in the past.   People were quite resourceful during these times.  

In the case of new trials, one CDMO reached out to us to see if we could deploy our clinical trial labeling platform in eight weeks. Both parties worked together, and we were able to meet their deadline. This was an incredible achievement that set new expectations for us with project timelines moving forward.  

Q. What impact has there been on clinical trial labeling?

Simon Jones: First, if we look at the pandemic effects, we've seen the need for pharma sponsors to use adaptive trials and then linked to that, to shorten the amount of time it takes to set up and start a trial. Now, of course, that demand and desire subsequently had an impact on labeling - it's putting pressure on a need to shorten the time for label and booklet design and production.   

Bob Bowdish: Turnaround times for labels are currently an issue in the industry. Multipage booklets are taking longer while study starts are happening sooner. One CRO had a December study start pushed into the next year due to delays with labels. This was problematic since this pushed planned revenue into the next year.    

Also, as mentioned before, there is an uptick in CDMOs adding labeling as a service. They see the current challenges with labeling as a strategic opportunity to win bids and add new customers. When they reach out to us, they are looking to differentiate themselves through speed and agility with their services. Smaller sponsors and CROs have shared that they experience delays due to vendors prioritizing larger clients. So, they are seeking other labeling service vendors or making plans to bring labeling in-house.  

Q. What does the rise in decentralized clinical trials mean for packaging and labeling?

Simon Jones: If it’s to support decentralized clinical trials, you’re likely to shift to an on-demand or just-in-time (JIT) packaging, labeling, and shipping supply chain model. I think we're distinguishing that ‘on-demand’ is where the request perhaps comes in via an IRT system as clinical packs are needed, whereas ‘just-in-time’ might be packaging and labeling packs to support a predefined production model forecast.    

Bob Bowdish: Speaking to customers, these concepts weren’t used before a couple of years ago, but since Covid, they have become a bit of a trend.    

Q. How has the growth in biologics impacted packaging and labeling?

Simon Jones: What we've seen is an increased need to shift production to much smaller batches owing to the need to minimize the drug product and comparator production, and associated waste, due to cost. The other aspect of this is of course, where stability data for biologics is not certain. It's much more likely that expiration changes will happen, and expiration extensions may be needed on biologics labels, which may mean there's a need for relabeling in the supply chain which is a challenge. Making it more complex is the EU clinical trial regulation No 536/2014 and Annex VI requirement that was introduced. This means that the latest expiration dates need to be labeled physically on the primary drug which can be a real challenge. This has pushed the pressure onto the need to use just-in-time packaging and labeling to make sure as you pack and as your ship, you're using the latest protocol data on your label to minimize the likelihood of needing to perform an expiry extension.   

Bob Bowdish: The cost of a biologic investigational medicinal product and branded comparators can be quite expensive. For example, in one Phase 3 study, the cost of a comparator alone was over $50,000,000. Addressing waste is much more of a priority now.  

The supply chain for biologics is experiencing growth and innovation. There is a worldwide expansion of infrastructure to manufacture, distribute, package, and label biologic study material underway.   

Q. How are service providers adapting?

Simon Jones: There has been an increase in investment in in-house labeling. There are several reasons for this. First off, they know that the request for improvements to the agility and the speed around label design, label production, and label changes is something that they can only facilitate and achieve if they have the labeling services, the labeling tools, and labeling expertise in-house. It gives them the ability to be responsive and provide a level of excellence around labeling capabilities.    

Another reason is that a lot of CDMOs see that pharma sponsors are always seeking to reduce the number of suppliers and service provider partners they have, so being able to offer a whole range of services themselves helps build better value add for their pharma sponsor clients. It also offers the CDMOs and the CSOs new revenue streams to reduce sub-contracting.   

Bob Bowdish: I think the current issue in the marketplace with label turnaround times, fear of waiting in line behind larger competitors for services, and this new mindset of “we can do it better” has its roots in the pandemic. Many clients look to leverage the current environment to differentiate themselves. We see this behavior with sponsors and service providers throughout the supply chain whether it be manufacturing, sourcing, distribution, or packaging and labeling.

Q. What does a clinical trial labeling application really do?

Simon Jones: I think many clinical trial suppliers aren’t necessarily clear on what the technology can do for them. In terms of PRISYM ID/Loftware’s applications, PRISYM 360 has been designed in collaboration with several clinical trial organizations and it's been designed to offer a level of automation to simplify and streamline some of the activities that can be manual, laborious, and quite risky. By being able to do it in the software, you can automate a significant amount of the label and booklet design and the approvals of these.   

A labeling application should offer the ability to perform phrase and translation management to reduce risk and reduce cost and if you're using phrases that have already been approved, then you’re reducing time.    

Similar to that, which is providing popular with our PRISYM 360 CDMO and CSO customers, is a regulatory rules engine within the application. This is a tool that our customers use to predefined rules for which content is required to be on each label depending on the drug product, the time period, and the destination country; this capability helps drive up compliance of clinical trial labels and booklets.    

The final one is offering flexibility in print production. Being able to support a range of print models such as batch production print or moving to on-demand product printing where you’re using an on-demand or just-in-time model.   

Bob Bowdish: Clinical trial labeling is challenging. Especially when it comes to labor-intensive components such as translations and the varying regulatory nuances seen with multiple country labels. Labeling platforms should address these challenging parts of the process through automation and support for industry best practices.    

Q. How easy is it to implement labeling applications?  

Simon Jones: We’ve seen over the last couple of years a shift from implementing applications ‘on premise’ to taking them as a Cloud service. It’s much simpler and a lot easier for CDMOs and CSOs as they don’t need to source, install, and operate hardware and operating systems. So, there’s been a big shift to Software as a Service and Cloud.    

The clinical trial sector also moved towards an ‘off-the-shelf’ software product approach. One thing we've seen is organizations that are much keener to collaborate with us on building new functionality to make sure it's fit for their need but also the need of the market, and part of that is building in some good default options which represent industry best practice and can also simplify assuring GXP compliance.  

This is proving useful to smaller organizations who want to adopt a labeling application as a base for their labeling services which will minimize the amount of effort and time it takes to operate.   

Bob Bowdish: This has played out in the marketplace. All the CDMO projects that I have been involved with have been SaaS deployments. Each component is blueprinted or templatized. This includes contracts, workflow, implementation, and training.  

Q. How do smaller CDMOs build the business justification for introducing labeling in-house?

Bob Bowdish: Often clients have decided to add labeling as a service by the time we meet with them. Outsourcing labeling for CDMOs is expensive, adds complexity, and the cost is typically passed on to the customer. The cost and time savings achieved by insourcing labeling provides the opportunity to add margin to projects and leverage a new source of revenue. The speed and agility achieved can be a competitive advantage and supports sponsor objectives to reduce third parties in the supply chain. The value of bringing labeling in-house is compelling and we have supported smaller CDMOs when asked this question.    

Q. Are CDMOs hiring translators to provide label translations?

Simon Jones: Yes, we do know some that do this, but a more common model is for CDMOs to provide external translators access to their PRISYM 360 application. This means all translations are performed within the application that the CDMO owns.    

Bob Bowdish: Most CDMOs are building translation libraries that will reduce translation costs and shorten the time it takes to produce booklet labels. One CDMO suggested that nearly 80% of the content on new labels is reused content which means they only need an author 20% to 30% from the start.