FaBioCell Area

GMP Production / Cell manipulation / ATMP

Working in a “GMP facilities” or “Cell Factory” became mandatory following the issuance of the European directive 2001/20 which established that the production of experimental drugs must comply with the Good Manufacturing Practices, normally indicated with the English acronym GMP (Good Manufacturing Practice). GMPs are the European guidelines whose application is mandatory at all stages of production of medicines, since they determine the criteria to which the pharmaceutical workshops must comply to guarantee the safety and efficacy of each medicinal product.

In Italy, the Italian Medicines Agency (AIFA) is in charge of determining the conformity of the pharmaceutical workshops to the GMPs and of granting the production authorization, following appropriate inspections.

Innovative drugs, such as cellular drugs derived from cancer patient cells, now constitute a promising field for the clinical development of personalized therapeutic protocols, also in consideration of their low toxicity profile and specificity of action. The current legislation establishes that cellular drugs are classified as “advanced therapy medicinal products” (ATMP), and requires that their production be carried out by highly specialized personnel in specially designed pharmaceutical workshops, based on the GMP criteria. As a consequence, the production processes and the rigorous quality controls, to which cellular drugs must be submitted before their use, must be carried out under conditions that ensure constant compliance with the pre-established specifications authorized by the competent authorities. The ATMPs constitute a new frontier of medicine and their experimental use must take place in the context of clinical studies defined and approved by the competent authorities.

Layout and classification of the production area

The Cell Factory is located in a dedicated building of the Istituto Superiore di Sanità of about 280 m². The area includes the production area, quality control laboratories, warehouse and staff offices.

The controlled contamination area, of about 90 m², includes 3 laboratories, 2 of which are dedicated to the production of drugs for cell therapy, and one dedicated to the execution of sterility assays on the products. According to the GMP standards, the cells are handled in laminar flow hoods, with Class A contamination level, placed in Class B environments. In addition to the basic equipment, the production area also includes incubators, centrifuges and microscopes, instruments for the separation of cell populations (1 Miltenyi Clinimacs Plus, 1 Clinimacs Prodigy, 1 Elutra Cell Separation System - Terumo).

The Quality Control area includes a laboratory for cellular and molecular biology assays, necessary to ascertain the identity, safety and functionality of the cell drugs produced, and a laboratory for the microbiological evaluation of environmental controls. Furthermore, there is a room dedicated to the programmed freezing of cell drugs and their storage in nitrogen vapors.