4. Handling
As shown in the process flow earlier in this article, manual handling is a prominent recurring process in the lifecycle of cell and gene therapies. Care must be taken to protect the packaging and cell and gene therapy material during handling and excess handling must be avoided to minimise temperature excursions. Temperature deviations can lead to safety concerns and impact therapeutic efficacy. Even a temporary rise in temperature would be able to cause cells to partially thaw, which could lead to altered functionality or even cell death. Errors involved with handling can pose a serious risk to patient safety and have severe financial implications due to product loss.
All staff involved in the handling of cell and gene therapies must be thoroughly trained in cold chain protocols and emergency procedures to avoid critical errors, with this training to be documented under the site Quality Management System (QMS). Maintaining a clear chain of custody through documentation in adherence to Good Documentation Practice (GDP) standards is essential to confirm that the cell and gene therapy material has been handled correctly at every stage of the process. Ensuring an accurate and complete audit trail will also be vital during a regulatory review in the event of an investigation or recall.
Specialist equipment can be used to minimise excursion times during handling from temperature-controlled shipping containers to storage containers and vice versa. For example, the use of cryocarts and dry ice containers allow operators to take material straight from a shipper or storage container and place it into an identical temperature environment, to verify the labelled information. It is of course necessary to ensure that all equipment used during storage, handling and distribution is validated or qualified for use. Details of equipment validated or qualified by a storage/distribution facility will be covered in a site Validation Master Plan (VMP), the responsibility of whom should be listed in your site standard operating procedures (SOPs).
An audit of a potential storage/distribution site is required prior to completing a service agreement, quality agreement and contracts. It is recommended that any audits are completed in person and not online. A tour of the facility will be invaluable to get an understanding of how the site’s standard operating procedures function, as well as the overall cleanliness of the site and potential out–of–specification risks regarding material handling.