Biologics may not be the ‘new kid on the block’ anymore, but they are becoming very popular, with biologics accounting for a quarter of drugs in the late-stage development pipeline. What does all of this mean for the future of medicine, the supply chain and clinical trials? Vanessa Dekou, Managing Director at CSI, provides a whistle-stop overview.
Small molecule drug development involves chemical synthesis following a reproducible, ‘recipe-book’ approach. Biologics, in contrast, are produced by a living host organism – often algae or bacteria – that has been genetically engineered to produce large, protein-based molecules, such as vaccines and monoclonal antibodies. Their larger structures and biological production make them harder to characterise, requiring more advanced spectroscopic and biophysical analytical techniques, while also making the manufacture of generics – called biosimilars (see Table 1) – more complex. An often-quoted description sums up the situation nicely: “In terms of size and rough complexity, if an aspirin were a bicycle, a small biologic would be a Toyota Prius, and a large biologic would be an F-16 fighter jet.”1
Magic bullets with a price tag to match
Biologics are the so-called ‘magic bullets’ in the drug industry – addressing many unmet clinical needs – and are likely to shape any vision of medicine in the future. However, bringing a biologic to market is expensive, with some estimates suggesting that the average daily cost of a biologic in the United States is $45, compared to $2 for a small molecule drug.6 How this all plays out in a world of increasing healthcare costs and patient demand for personalised treatment is a matter for governments, hospitals, pharmaceutical companies and, in some countries, insurance providers to debate.
The first biologic
Recombinant human insulin – used to treat type 1 and some cases of type 2 diabetes – was the first commercially-available biologic, entering the market in 1982, following its successful production within E. coli and Saccharomyces cerevisiae cells. Since then, other biologics have emerged and are being used to treat diseases such as Crohn’s, rheumatoid arthritis and psoriasis, among many others.
Increasingly personalised and precise
Like conventional small drug development, some biologics adopt a ‘one size fits all’ approach in which a whole population is targeted using a single therapy. Yet the true opportunity for biologics lies in the ability to target diseases at the individual level, considering a patient’s genome and embedding genomics across the drug discovery pipeline, offering a future of personalised and increasingly precise medicine. What effect this might have on disease classification is fascinating. A move towards personalised medicine may well lead to an increase in ‘rare’ diseases, as our ability to differentiate on an individual, patient level improves and subdivisions in diseases emerge.
What does this mean for clinical trials supplies?
The supply chain is growing colder
Clinical trial supplies need to be prepared for the supply chain to grow colder. Unlike many small molecule drugs, biologics require storage and transportation at cryogenic temperatures, often around 2-8 °C, and suppliers need to evaluate the whole supply chain from production to collection to distribution. A lorry is no longer just a lorry – it’s a mobile, cold-storage facility – and the demand for robust, accurate IT systems for GPS and temperature compliance tracking will only increase. The stakes are higher for biologics if the supply chain breaks down, with losses in the millions of dollars if a biologic drug is compromised in transportation.
The supply chain is growing more complex
There are a number of complexities that we face in comparator sourcing supplies, which require careful and early planning. For starters, sourcing biologics for clinical trials is more challenging due to their higher cost and limited availability; it’s quite different from dealing with aspirin! In addition, distributing the biologic to the clinical trial site is not the only requirement, as the biologic will likely need to be accompanied by markers. For example, there is little benefit in trialling Avastin® (bevacizumab) for breast cancer treatment unless the antibody markers indicate that the patient will respond to the treatment. Production of these markers is likely to be at an entirely different site to the biologic production, so multiple, unbroken cold supply chains need to be coordinated to arrive at the same site on time.
Looking to the future
Biologics is a growing industry, and we’re looking forward to the demands and challenges of coordinating a global cold supply chain. We’re excited to play our part in the development of precision medicine, supporting clinical trial sponsors to source hard-to-find comparators and protecting their trial from disruption, while bringing our scientific expertise to these complex studies We know what it takes to manage tight deadlines and align production, packaging and transportation to deliver the very best service.
If you’re looking for a comparator sourcing partner for your next clinical trial, let us know – we’re keen to help and committed to deliver more accessible healthcare for all.
5 THE IMPACT OF BIOSIMILAR COMPETITION IN EUROPE, IQVIA, October 2019.