Horizon scanning

There were 30,984 trials registered on clinicaltrials.gov in 2018. The website is only for researchers in the US and is not infrequently criticised for its ongoing, userunfriendly drift into irrelevance and obsolescence. And still, last year, it recorded the launch of almost 31,000 studies, which will together affect countless patients through thousands of investigational sites worldwide.

That’s a lot to get your head around, so let’s take just one of those locations. “Normally a site that conducts clinical trials works with multiple companies and runs multiple studies,” writes Kristen May, director of clinical supply chain at Amgen, in a GS1 publication on the topic. It could be one of the world’s largest medical facilities, a state-of-the-art research university or a single committed practitioner; it could be any blend or combination of the above. Whatever it is, it’s in a relatively slow period. The site is running 100 simultaneous studies on drugs from 10 different sponsors. That means it has to contend with 10 different proprietary approaches to packaging, labelling and serialising 100 trials worth of investigational products.

The strain of just using the right equipment seems excessive. As May pointed out, “If they’re running studies from 10 companies, the research pharmacy may have 10 different scanners they need to use.”

It can be considerably more complex. “We have about 1,200 different line items of inventory in our research pharmacy,” adds Caroline Harvey, research pharmacy manager at the Dana-Farber Cancer Institute in Boston, in the same report. “In fact, we have as many inventory items as our commercial pharmacy.” There are about 750 active drug studies at Dana-Farber, and, as Harvey notes, “In the research pharmacy, a lack of standardisation among the different pharmaceutical sponsors translates to each sponsor doing things in a different way, and that’s a significant challenge as well as a potential medication safety issue.”

A labyrinthine process

Within each sponsor’s labelling paradigm, some products have no barcode identifiers, and some packages have multiple. It’s common for companies to barcode packaging elements for internal process control, for instance. Without any wider agreement on how these codes are allocated or displayed, however, once those packaging elements, and the products they contain, move into the supply chain, the array of proprietary identifiers just create confusing opportunities for costly errors. At present, it’s not difficult to envisage a couple of small mistakes resulting in investigational products getting sorted and distributed according to their packages rather than their intended action.

750
The approximate number of active drug trials at Dana-Farber Cancer Institute in Boston.
Dana-Farber Cancer Institute

Moreover, when ID numbers are designed to communicate internally, but are not globally unique, there is a chance of the same identifiers appearing as part of different companies’ investigational product kits. A string of digits might be generated for the purposes of order, but intention counts for nothing as soon as the context supporting it changes.

80%
Percentage of pharmaceutical product packages in the US that don’t meet the requirements of the Drug Supply Chain Security Act.
GS1

And that’s without mentioning the placebos, comparators, personalised medicines, and procedures for blind and double blind studies that have to be conveyed and managed along the investigational supply chain.

And as Tania Snioch, healthcare director at GS1, the not-for-profit responsible for developing and maintaining global standards for business communication, writes, despite all that effort, “It might happen that the wrong product is picked for distribution to a trial site or even administration to the patient, or it might be that trial participants have similar personal details and could be mistaken for each other. Not often, but sometimes, mistakes happen – to err is human.”

In March this year, the first global ‘Identification of investigational products in clinical trials application standard’ was published by a GS1 working group chaired by Centre Hospitalier Victor Dupouy, Pfizer and Sanofi. The fruit of nine months of weekly meetings between 60 representatives from pharmaceutical companies, hospitals, IT solution providers, contract research organisations and others, the standard is being touted as the first step towards consistently identifying investigational products along the entire supply chain.

“The industry brought knowledge about clinical trials, and GS1 brought knowledge about global standards for identification and barcoding,” recalls Snioch. “That meant that there were a lot of insights.”

Many of them focused on considerations specific to clinical trials, including the level of disclosure on packages for blinded and double-blinded trials, space constraints for small products requiring a lot of information on the label, resource pooling and more. Equally, numerous queries specific to the nature of GS1 standards had to be resolved. Looking back, Snioch highlights important discussions around the organisational responsibility for allocating a global trade item number (GTIN) to a product and how GTINs should be employed when pre-existing commercial products are used as part of a trial.

Although this is quite explicitly the beginning of a longer process for investigational products, it follows closely on the February 2019 deadline for the implementation of the EU’s Falsified Medicines Directive. All prescription medicines in the EU are now serialised on an individual product basis. In practice, this means each is marked with a GTIN, which includes a company prefix identifying the manufacturer, and an item reference, which uniquely identifies the product from the perspective of a consumer. Encoded into a barcode, GS1’s most famous symbol and standard, with a serial number that identifies the specific package dispensed to the patient, the GTIN makes it simple to identify a specific container of a product and access information about it with one universal scanner.

By 2020, such serialisation is expected to cover 80% of the world’s commercial drug supply, with healthcare systems in 65 countries worldwide implementing GS1 standards. While the Falsified Medicines Directive was passed in 2011, and the US Drug Supply Chain Security Act in 2013, the GS1 clinical trials working group only began to come together in April 2017. There had been some preparatory work done within the French and US markets prior to that date, but as a whole, the clinical trials supply chain has received far less attention than its commercial counterpart.

The difference is clear

Investigatory products are different from commercial medicines, and it’s churlish to read Van der Horst’s comments as if they apply equally to both spheres. As Snioch is quick to point out, “The benefits depend on the drivers.” She gives another example to demonstrate this. “If you think about patient safety in a hospital environment, then there are multiple examples where the use of barcodes can ensure the right product is in the hospital for the patient when they need it, that the correct medication is administered (with a barcode scanning step at the patient bedside), or that the correct medical device is recorded in a patient record and able to be identified in the case of recall or withdrawal.”

In terms of trials, “There’s a lot of manual data entry and a significant amount of data that’s crossing systems,” explained Jeff England, director of global clinical supply for MSD, upon the release of the application standard in March. “With GS1 standards, we wouldn’t have transcription errors that we typically look for on the back end, nor would we spend so much time verifying and validating data.”

Other sponsor and supplier benefits include the ability to compile all that fiddly data more quickly in the first place, enabling full supply chain traceability and easier sharing of information across the clinical research ecosystem (with a commitment to interoperability on the other side, standards might even make clinicaltrials.gov easier to use.) At trial sites, global standards save time, improve inventory management, limit the need for internal relabelling and transcription, and facilitate innovations development that leverage the standardised barcode format. For all of that, what Snioch sees as the most important benefit isn’t so tangible. In her words, “Adopting the GS1 standard adds an element of trust at all levels of the supply chain – a trust that ultimately extends to the patients themselves.”

80%
The world’s commercial drug supply is expected to be serialised by 2020.
Pharmaceutical Track&Trace

“Once we standardise data, a big benefit is the work progresses faster and is more reliable,” agreed England. “Data is compiled quicker, accelerating our submissions to the regulatory agencies. Yet, in the end, it’s the patients who will benefit the most – something that we all get behind.”

Others went further in looking forward to the effects of increased adoption of the GS1 application standards. “If we harmonise our operations on standards, we are not just benefitting the drug industry or the research community, but also all the doctors, hospitals and other healthcare facilities that scan barcodes,” said May. “It doesn’t make sense to use different codes. It shouldn’t matter if it’s a clinical product or a commercial product. They should be able to follow the same approach to identify a product.”

It’s on that basis that Snioch points out that any sponsors interested in implementing the standard are already using a similar version of it commercially. “That means they have internal expertise they can leverage,” she notes, alongside recommending downloading the standard from the GS1 website and contacting local GS1 member organisations. “Also, people should talk to those contacts they know who are members of the work group, as listed at the start of the application standard. These people are really well informed and, in my experience, willing to share their knowledge.”