By Michael Blackton, VP QA CMC at Adaptimmune
Maintaining clinical trials during the COVID-19 pandemic has presented quite a challenge for those companies exploring novel therapies. Unlike traditional biotechnology products, supply of autologous therapies is complex in that each patient’s drug supply is unique to that patient. These therapies require that a patient’s drug supply is manufactured in real time, and unlike traditional biologics where a single batch could potentially supply hundreds, or even thousands of patients, for us one batch is one patient. Even the shortest disruption could have a devastating impact on the business. It is important to understand that the pandemic response required a high level of resilience and innovation so a pivot to the new reality would not delay patient dosing.
As the head of Quality at my firm, there were a few areas that were important in our response to the pandemic. Ensuring adequate personnel on site to perform those tasks that must be done in person, ensuring the appropriate technology was employed to empower remote work, and fast and efficient evaluation of quality issues as they arise were all major considerations. It was fortunate in our case that we had done a fair amount of business continuity planning before the pandemic, so we had a game plan that addressed roles, responsibilities, and communication paths which was critical in defining the tailored response to this disaster. While the plan did not specifically address the pandemic, it was used to facilitate effective management of the crisis.
Ensuring the right people were on site was a major concern considering the state and local requirements for social distancing and work from home. In our case, this analysis resulted in a small number of quality reviewers and minimum staff in the Quality Control Laboratory. While we successfully navigated physical controls for social distancing and plans for contact tracing, we also had to consider how we would approve documentation when those approvers were largely working remotely. We have electronic systems for document management which includes review and approval of documents like SOPs and master batch records, but not the myriad of forms that are physically signed by a QA or QC professional during the course of a workday. This includes shipping authorizations, manufacturing forms, and test results. In our case, we had recently implemented an electronic system that applies remote signatures on scanned clinical documentation. Fortunately for us, we had anticipated the system’s use in the manufacturing side, so porting the system to GMP was an easy thing to do.
In order to facilitate the requirements of the new reality we knew we had to adequately address quality issues as they arose. Of particular note were the possibility of symptoms or even a COVID-19 diagnosis among the critical personnel on site. To address this, we developed a comprehensive risk assessment that would be preformed to evaluate the impact on manufacturing. On the supply and procurement side, we knew that because of the shortage of PPE, cleaning agents, and sanitizers, alternatives to our regular supply would be required. Using similar risk assessments, we were able to quickly evaluate options for alternatives.
I would recommend that organizations develop contingency plans that ensure essential activities are maintained across a mix of potential disaster types. In the case of pandemic, that plan must include a determination of what parts of the business are considered essential and include those activities that must be performed on site vs remotely. For any contingency, the plan should define clear roles and responsibilities for responding to a crisis. Finally, these plans should be regularly reviewed, revised if needed, trained on, and practiced so that when needed, the plan is implemented quickly and efficiently.