The viral vector bottleneck has been a well-documented challenge to the cell and gene therapy sector in recent years. Development of cell and gene therapies has been highly successful, with increasing numbers of therapies reaching approval and late-stage clinical trials. Adeno-associated viruses (AAV) are a critical component of research and development of these therapies. However, AAV production has not kept up with demand, and the bottleneck becomes progressively more of a challenge.
Viral manufacturers are dedicating significant resources to adapt key steps of production for large-scale manufacturing. One solution to this is developing transfection reagents to achieve transient transfection, a critical step that is indispensible for a reliable AAV manufacturing process. Polyplus-transfection® is currently launching a new transfection reagent for large-scale AAV manufacturing. However, achieving supply of a brand new product critical to the success in solving the viral vector bottleneck during the COVID-19 pandemic and global lockdown is a considerable challenge.
The COVID-19 pandemic is an unparalleled situation of international proportions. Many industries have to worry about keeping supply and manufacturing chains going to keep companies in business. The cell and gene therapy sector has the added responsibility to maintain the development of life-affecting and life-changing therapies. Delays to therapeutic development cost lives of patients, many of which have no alternative treatment options. To maintain supply of critical transfection reagents, Polyplus-transfection® has had to take a number of steps.
The origin of COVID-19 in China allowed other global governments to see the potential challenges resulting from the outbreak, as well as take conceivable necessary steps to prevent the further spread of the disease. It also gave critical time for companies and supply chains to take steps to mitigate risk prior to the global lockdown. The shortage in reagents to develop COVID-19 tests, vaccines and therapies has been well documented. It remains as essential to continue supplying reagents for developers of cell and gene therapies for cancer, and other diseases.
For a company such as Polyplus-transfection®, as a vital supplier to so many parts of the cell and gene therapy sector, it is important we plan for many potential eventualities. There have been a number of times since we were founded in 2001 that the world has experienced challenges to global supply lines, from the shock of the attack on New York in September 2001, to the eruption of the Bardarbunga volcano in Iceland in 2014. Whilst these caused short-term disruptions to global supply lines, outside the risk of wider global conflict, there have been several cases of other serious potential challenges. SARS has given a demonstration of how a coronavirus can spread and the measures governments might be forced to take.
When infection spread in China, using the short time available as a warning before the COVID-19 infection reached Europe and became a pandemic proved critical. The biggest challenge for companies supplying the cell and gene therapy sectors has been maintaining supply chains, both for incoming materials, as well as outgoing products. It was inevitable that obtaining all stock from raw materials to laboratory equipment might produce a major obstacle as global supply chains narrowed. As a result, it was essential to considerably increase stock levels before the shut down really took effect.
At the other end of production, it was very important to move as much finished product as possible to different locations around the world to be ready to supply different customers globally. This especially related to our lead GMP product, PEIpro®-GMP, to maintain supply of transfection reagents for late stage clinical trials and commercialisation of cell and gene therapy products.
By increasing communication with our partners, including couriers and transporters worldwide from the offset has also proved vital. As a result, we have been able to maintain global shipments. Appointing and maintaining relationships with reserve transporters has also proved important. As a transporter in one location is unable to continue operations, another is immediately appointed.
Internally within the operation, it is vital operationally we are affected as little as possible by the lockdown within France. We have had to implement and adjust other parts of our crisis plans. There have been a number of increased safety rules implemented on site to minimize the risks of COVID-19. With laboratories and research and development facilities on site, and working with a number of viruses on a daily basis, we are far more used to the ongoing importance of good hygiene as a matter of course than companies in other industries. However, these safety rules had to be adjusted and tailored to prevent virus infection entering the building from without, as well as leaving the building from within.
As with many companies across Europe, we immediately set up home offices and working practices for all positions not directly involved with scientific operations in order to protect the employees of the operational teams. In addition, a regular turnover of employees was immediately implemented on site to minimize the number of people on the site at the same time. We’ve also had to divert significant additional resources to different sectors of the company. The supply chain department has been bolstered for managing shipments, with additional resources needed to manage reception and shipments of goods, as well as the significant increases in documentation. Backup plans and staff are needed should any employees in this area need to self-isolate. Daily management meetings have followed progresses and changes in stock and demand. The operations team has received daily reports to inform them about resultant changes and anticipating risks. We have also appointed an international crisis management team that interacts daily to assess immediate issues, threats and plans for any future contingencies.
The preparation and enhancing prior contingency planning we have been able to achieve has meant we have continued and maintained operations. Essentially, we have not had one member of staff diagnosed with COVID-19 so far. Indeed, in the middle of the crisis, we have managed to launch FectoVIR®-AAV, a reagent for improving AAV (adeno-associated virus) production for large-scale manufacturing. This will provide, in the teeth of a global pandemic, a major international solution to the viral vector bottleneck.