Taken from an article published in the April edition of the European biopharmaceutical publication MedNous.
As far as we currently know, the first reported case of COVID-19 can be traced back to November 2019, with the pandemic originating from Hubei province in China. As of 8th April, the World Health Organisation had reported 1,279,722 confirmed cases of COVID-19 and 72,614 deaths. This compares with 118,326 cases and 4,292 deaths when the disease was declared a pandemic on 11 March. And transmission of the virus is still taking place at time of writing.
The infection has placed unprecedented strain on worldwide healthcare systems, expanding critical care into operating theaters and hastily constructed temporary hospitals. It would be dangerous to try and predict how the pandemic will change the way in which we live and how healthcare systems will cope.
In this article we discuss some of the logistical challenges facing the developers of cell and gene therapies amidst the pandemic. At the best of times, administering advanced therapies such as CAR-T cell treatments is challenging. These therapies have circular supply chains, with one of the two key raw materials for manufacture being obtained from the patient who has been prescribed the treatment. Typically, patients are treated some distance away from the site of manufacture. Therefore, these autologous therapies have two patient-specific logistical steps: moving the patient’s own cells to the site of manufacture and bringing the therapeutic agent back from the plant to the patient’s hospital. The therapy and its starting material can be temperature-sensitive, so transport must be undertaken in temperature-controlled shipping systems and potentially with transit times as short as 48 hours.
The pandemic has led to a reduction in commercial aviation. It has also decreased airfreight options for advanced therapies and their associated starting materials. This means that collection times for starting material may need to be adjusted to harmonize with alternative departure times, even when the starting material has a short shelf life. As a company involved in logistics, we believe that alternative methods of transport should be considered if possible. A feasibility study should be undertaken to examine if starting material or drug products can be moved by road transport alone.
For some advanced therapies, manufacturing must begin within 48 hours of obtaining starting material. It is necessary to ensure that manufacturing assets are available before the collection of starting material. Scheduling manufacture of advanced therapies during the pandemic is proving to be more challenging than usual. Therapy providers need to work closely with their suppliers to ensure that there are enough manufacturing technicians available to make the product. This can be a problem as the technicians may be absent due to the illness.
Access to starting material and delivery locations for the final therapy should be available at hospitals, even those treating COVID-19 sufferers. The highly contagious nature of the coronavirus has led to most hospitals imposing strict access control. While couriers may have access to areas for collections, this access may be limited, requiring changes to collection protocols. The couriers whom I have contacted understand the risks associated with access to hospitals with potentially infectious patients and have issued protective equipment to their drivers.
There is also a possibility that scheduling advanced therapy treatments may be postponed due to the susceptibility of immuno-suppressed or immuno-compromised patients to SARS-CoV-2. This is because some CAR-T cell and other advanced therapy treatments require patient preconditioning to deplete endogenous lymphocytes.
Interestingly, tocilizumab and interleukin-6 antagonist originally developed to treat rheumatoid arthritis and used to ameliorate chronic inflammation associated with cytokine release syndrome, is also being administered to patients with COVID-19 who exhibit sever inflammatory responses to their infection.
Some advanced therapies have significant side effects that need to be managed. As mentioned above, some patients receiving CAR-T cell treatments may suffer from cytokine release syndrome, for which severe cases require intensive care beds to support the patients. Regrettably, COVID-19 has taken its toll on hospital capacity and the availability of intensive care beds. As a result, difficult clinical decision will need to be made when considering treating a patient with a therapy whose side effects may require intensive care treatment.
Prior to COVID-19, the most severe disruption to supply chains that the pharma industry faced was the eruption of the Icelandic volcano Eyjafjallajokull, which affected air travel for weeks. This was a challenging period. At the time I was managing a clinical trial for an autologous therapy, manufactured in the US but with the treatment centers in Europe. We managed to minimize the disruption by routing samples of the therapy via Madrid as Spanish airspace was still open, enabling us to bring the drug and starting materials across the Atlantic. By understanding the supply chain and the product’s stability characteristics, it was possible to plan for an alternative route. But changes to supply cycles should be thoroughly assessed using multi functional risk assessments.
It will be essential for the industry to undertake a through review of how it can continue operations during a pandemic. This will be necessary in order to carry on saving the lives of patients under a variety of conditions. The risks of pandemics are constant, so this is an essential undertaking.