Europe – Comparability considerations for Advanced Therapy Medicinal Products : Q & A

CHMP scientific advice questions are often related to the suitability of comparability proposals following changes to ATMP manufacturing processes or due to introduction of additional manufacturing sites. Manufacturing process changes may encompass improvements/change in equipment, raw materials and critical starting materials such as the cells or the vector or their suppliers, manufacturing process scale or product stability. Such changes are frequent, especially in the early stages of development of ATMPs.
Every change in manufacture should be done in accordance with GMP. The criticality of the changes and the estimation of their impact on the characteristics of the product should determine the amount of comparability data needed. Where applicable, the Variation Regulation1 (for authorised ATMPs) orthe clinical trial framework (for investigational ATMPs) should be followed.
A suitable comparability program is required to support the introduction of changes during the development stages of an ATMP. The acceptable level of flexibility is progressively reduced from the non-clinical stage to the pivotal clinical use. Comparability is also an important tool to support changes after marketing authorisation where the process and the product are expected to be well defined and appropriately controlled by quality specifications and characterisation tools…