Theme 5: Tissue Engineering for Regenerative Medicine

Prospective manufacturing models

Existing regulatory structures, internationally, require the establishment and maintenance of comparability between manufacturing sites. Failure to achieve this means products may not be able to proceed along the development track, and patients’ access to clinician-led autologous cell-based therapies will be in jeopardy. Hourd et al7 in addressing this problem, developed three prospective manufacturing models for the scale-out/roll-out of MTMM clinically led autologous cell therapy products. Fig 9, which can be linked with the The Vision in fig 7 on the previous page, is an extremely distilled picture of the three models:

  • Model 1 Limited cell expansion Minimal number of population doublings/reduce manufacturing complexity/reduce biological-drift.
  • Model 2 Incremental validation Manufacture MTMM cellular products at multiple sites/release proportional to ‘degree of risk’ ex product release specifications in licence/incremental continuous validation after marketing/achieve comparability easily between manufacturing sites [under single-product licence] ex reduced need for characterisation and validation studies.
  • Model 3 Closed or functionally closed automated manufacture Manufacture MTMM cellular products within a closed and automated process [‘GMP-in-a-box’]/achieve comparability easily between manufacturing sites [under single-product licence] ex reduced need for characterisation and validation studies/only the machine would need validation for a chosen indication or protocol and not the sites in which it would be used.

Fig 9 Manufacturing models permitting roll-out/scale-out of clinically-led autologous cell therapies

The respective models’ prospects for meeting the comparability challenge were tested with a small panel of US and UK ‘thought leaders’. Deliberations continue.


7 Manufacturing models permitting roll-out/scale-out of clinically led autologous cell therapies: regulatory and scientific challenges for comparability: Paul Hourd, Patrick Ginty, Amit Chandra, David J.Williams: Cytotherapy, 2014; 16