Clinical and Medical Research its ability to reduce direct and indirect costs associated with cancer and genetic disorders and reduce the costs associated with healthcare plans, as the cost of using precision medicine treatment will be lower than the cost of prescribing treatments that are neither biomarker nor population specific and may be ineffective. The shift in demographic has also moved the focus from tackling infectious diseases to managing long-term conditions. The emphasis on health management and wellness has helped shape a new approach to engaging people before they become patients. Resultingly, the healthcare industry is focusing increasingly on prevention – a key benefit of precision medicine. The popularity of targeted therapies is another contributing factor, with biologics dramatically increasing from 5% of new drug approvals in the 1990s to making up a quarter of today’s pharmaceutical market. Regulation is rapidly evolving to accommodate this surge in growth. In the US, the development of a companion diagnostic is now an intrinsic part of the FDA’s approval of precision medicines, which are deemed safe and/or effective only if the patient has a certain biomarker. Other factors contributing to market growth include significant investment in biomarker and targeted therapy R&D, due to the profit potential and opportunity to uncover new revenue streams. New technology is another driving force, with next generation sequencing underpinning many emerging diagnostic tests. The emergence of value-based healthcare models, that reward value (patient outcomes) over volume is also having a notable impact. A final contributing factor that we cannot ignore is the impact of COVID-19 on the clinical trials’ landscape. The urgency surrounding vaccine development, the disruption to supply chains and R&D pipelines and the increase in public awareness, has had an unprecedented effect. Leading industry commentators have suggested that working under a spotlight, navigating protracted economic uncertainty and embracing technology have been core learnings from a landmark year.
be the opportunity to hit the reset button and leverage learnings to create competitive advantage. Through continued collaboration across the supply chain, greater focus on protocol development with the patient's outcome in mind, prioritisation across the value chain, investment in technologies to support the future way of working, and a shift to portfolios in newer modalities (i.e., cell & gene therapy) sponsors will increase their likelihood of thriving in a post-pandemic era of drug development. Exploring the complexity of advanced therapy supply chains The complexities associated with operating advanced therapy clinical trial supply chains are vast and must be approached with caution in order to avoid negative impact to patients and commercial performance. There are several fundamental issues that risk compromising a sponsor’s ability to compliantly and cost-effectively deliver the right drug, to the right patient at the right time and temperature. Limitations relating to recruitment, forecasting and drug stock can make it difficult for sponsors to effectively match supply with demand. Limited product stability, retest dates and forecasting can also raise the financial stakes for sponsors and demand a right-first-time approach to minimise waste and promote product integrity throughout the supply chain. Pressure to accelerate manufacturing and accommodate personalised packaging and dosing criteria also warrants careful planning and precise execution, as does implementing appropriate handling and optimised shipment protocols to effectively mitigate temperature excursions throughout global cold chains. While challenges such as aggressive timelines, inadequate supply chain visibility and the need for controlled temperature handling are not unique to precision medicine, they can be exacerbated where advanced therapies are concerned. Take for example, autologous therapies that require a rapid, patient-led cycle time
from collection to injection, temperature control, full track and trace of material and multi-site collection and distribution. This requires a carefully considered and robust end-to-end strategy, underpinned by effective technology. Digital supply chain and logistics systems will help sponsors of trials involving advanced therapies to effectively manage the heightened risk by providing real time data exchange between clinicians, manufacturing sites and carriers. Another high-risk area in autologous therapy supply relates to regulation so early regulatory planning is critical. This can be achieved by taking a holistic approach to compliance management and obtaining local regulatory requirements and importation guidelines. Sponsors should ask themselves a series of questions to establish whether ATMPs are defined in legislation, whether there are additional regulatory requirements for gene and cell therapy and tissue engineering and if there are specific safety or legal restrictions for GMOs and viral vectors. If sponsors are planning on conducting trials within the EU, it is also advisable to solicit feedback from a Qualified Person. Allogenic therapies, utilising donor tissues, bring similar supply chain challenges. As with all stem cell therapies, allogenic products must be manufactured under Good Manufacturing Practices. The scale up of manufacturing for allogeneic cells is similar to techniques used to make protein drugs and other large-scale, cell-derived materials. However, there are some nuances to be mindful of. For example, while both therapies use similar technologies common to the growth of cells, the scale is different. Allogeneic therapies are ‘off the shelf’ and used to treat many patients, so more time is available to quality control the product prior to administration. That said, sponsors will need to introduce flexible manufacturing platforms to support growth of living cells for a larger patient pool. Low stability profiles and restricted ‘time out of conditions’ will pose challenges from production through to patient administration, with narrow
For sponsors, the silver lining of a global pandemic that caused untold disruption will 40 INTERNATIONAL PHARMACEUTICAL INDUSTRY
Autumn 2021 Volume 13 Issue 3