The specialized nature of cell and gene therapies (CGTs) requires that they be delivered to single patients or in low batch numbers. Manufacturing CGTs at scale is critical to industry success, but doing so at an economically viable cost is a key obstacle. Today’s therapies cost between US$400,000 and $3.5 million per patient, largely because of the need for highly skilled workers to deliver those innovative drugs. The CGT industry has innovated across all areas of production, from collection of patient material to autologous manufacturing.

Strengthen Data Management and Integrity
Data integrity continues to be a priority area for good practice (GxP) inspections. Deadlines for replacing noncompliant record and data-management systems have passed, and as a result, organizations in late-phase advanced therapy investigational medicinal products (ATIMPs) and commercial manufacturing are obliged to operate electronic systems. Among further points of consideration for the CGT sector, two unique identifying codes should be used to label and verify starting materials and intermediates at each processing step up to release, as per the new FDA recommendation. That may become a de facto standard that supports electronic systems and affects existing standards such as ISBT128 and FACT-JACIE.

To reduce risk, organizations need to implement time-interval control using robust systems for testing, cryopreservation, quality assurance (QA) review, release, and shipping. More data will influence decision-making by means of measurement recommendations for starting-material quality indicators, vector copy numbers, and potentially complex combinations of potency assays that may require multistage support of electronic-decision algorithms. The recommendation to split starting material to provide process validation comparators has implications for data retrieval, blinding, and allocation of viewing permissions, whereas using healthy donor material may require arrangements and systems to change for consent and data management.

Centralized and Decentralized Manufacturing
The UK Medicines and Healthcare products Regulatory Agency (MHRA) is expected soon to release guidance on point-of-care manufacturing consultation, which will have multiple implications for the ATIMP sector in the country (1). The MHRA’s proposed “hub and spoke” licensing arrangements will require overarching quality management. Digital systems will need to provide coverage/oversight across all collection, processing, and clinical-use sites. For example, companies should demonstrate timely critical quality attribute (CQA) comparability between manufacturing sites. Consistency in audit, review, and release procedures based on robust data analysis also is important because using paper batch records takes considerable time. Accreditation through an organization like the joint committee of ISCT Europe and EBMT (JACIE) is likely to influence a site or organization’s risk rating, so data management should include outcome metrics across clinical sites, ideally with findings for both upstream collection and processing facilities.

Delivery Solutions
My company is a software provider that can enable organizations to deliver CGTs to hospitals using digital solutions to support regulatory compliance and traceability of shipped drug products. The goal is to accelerate learning and reduce the risk for CGT manufacturers that want to hasten delivery and lower the cost of goods (CoG). A team of experts from both the CGT and technological industries has commercialized an enterprise-scalable digital platform using digital technologies from Amazon Web Services (AWS) and Google. Autolomous secured grants to collaborate with select partners, including the UK National Health Service (NHS) network of Advanced Therapy Treatment Centres, which are tasked with accelerating CGT clinical adoption. The company continues to build partnerships and share its platform to CGT developers from academia, biotechnology companies, and contract development and manufacturing organizations (CDMOs) working across multiple CGT targets.

Reference
1 Consultation on Point of Care Manufacturing.Government Digital Service: London, UK, 25 January 2023; https://www.gov.uk/government/consultations/point-of-care-consultation/consultation-on-point-of-care-manufacturing.

Kwok Pang is chief operating officer at Autolomous Ltd., 17 Hanover Square, Mayfair, London, UK; 44-203-900-9245; [email protected].