Limits...
How we make cell therapy in Italy.

Montemurro T, Viganò M, Budelli S, Montelatici E, Lavazza C, Marino L, Parazzi V, Lazzari L, Giordano R - Drug Des Devel Ther (2015)

Bottom Line: In the 21st century scenario, new therapeutic tools are needed to take up the social and medical challenge posed by the more and more frequent degenerative disorders and by the aging of population.The recent category of advanced therapy medicinal products has been created to comprise cellular, gene therapy, and tissue engineered products, as a new class of drugs.Our hospital took up the challenge of this new path in the early 2000s; and herein we describe the approach we followed to set up a pharmaceutical-grade facility in a public hospital context, with the aim to share the solutions we found to make cell therapy compliant with the requirements for the production and the quality control of a high-standard medicinal product.

View Article: PubMed Central - PubMed

Affiliation: Cell Factory, Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.

ABSTRACT
In the 21st century scenario, new therapeutic tools are needed to take up the social and medical challenge posed by the more and more frequent degenerative disorders and by the aging of population. The recent category of advanced therapy medicinal products has been created to comprise cellular, gene therapy, and tissue engineered products, as a new class of drugs. Their manufacture requires the same pharmaceutical framework as for conventional drugs and this means that industrial, large-scale manufacturing process has to be adapted to the peculiar characteristics of cell-containing products. Our hospital took up the challenge of this new path in the early 2000s; and herein we describe the approach we followed to set up a pharmaceutical-grade facility in a public hospital context, with the aim to share the solutions we found to make cell therapy compliant with the requirements for the production and the quality control of a high-standard medicinal product.

No MeSH data available.


Related in: MedlinePlus

Example of the training program for the Cell Factory personnel (first page of the training form).Abbreviations: QA, quality assurance; QP, qualified person; SAS, surface air system.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4548721&req=5

f2-dddt-9-4825: Example of the training program for the Cell Factory personnel (first page of the training form).Abbreviations: QA, quality assurance; QP, qualified person; SAS, surface air system.

Mentions: The GMP staff is the crucial point of any good facility. Staff must have the necessary skills, be properly trained and always updated both in theory and in practice on the concept of quality assurance and standards of GMP. We planned an initial training and an ongoing training, as requested by the GMP guidelines (EudraLex – Vol 4, chapter 2)1 with frequent staff performance and training courses. At our facility, the training plan follows an annual schedule and it is differentiated by various topics for both production and QC staff: an example of training program is reported in Figure 2. In addition, special training schedules are set up for the technical, maintenance, and cleaning personnel. All the GMP staff duties, including the management staff and the QP, responsible for implementation and enforcement of GMP are specified in our job descriptions. Among the various activities of the initial training, microbiological validation of the operators is also crucial: only after successfully overcoming the microbial validation including aseptic gowning and operations also with media fill (as thereafter illustrated) the production staff is authorized to work in aseptic procedures. Moreover, the single operator involved in the production process is constantly monitored at the end of each work session. The personnel microbiological monitoring consists in testing the forearms as well as the five fingers. All the plates are incubated at 20°C–25°C for 5 days and then at 30°C–35°C for 5 days. The results are expressed as TAMC (total aerobic microbial count) and as UFC/plate (unit-forming colony) as requested by EuGMP/Annex1. Autochthon strains are tested in the validation of final product sterility testing. Every 3 months environmental microbiological, particulate, and staff data are collected in specific forms (Figure 3) in order to prepare our periodic reports (Trend Analysis). These trend analyses are built according to the theory of control of Shewhart charts, to fit the warning and alarm limits to the real situation of the production site. Adequate alarm and action limits have been established and are continuously updated to determine the immediate investigation and appropriate corrective action in case of deviations.


How we make cell therapy in Italy.

Montemurro T, Viganò M, Budelli S, Montelatici E, Lavazza C, Marino L, Parazzi V, Lazzari L, Giordano R - Drug Des Devel Ther (2015)

Example of the training program for the Cell Factory personnel (first page of the training form).Abbreviations: QA, quality assurance; QP, qualified person; SAS, surface air system.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4548721&req=5

f2-dddt-9-4825: Example of the training program for the Cell Factory personnel (first page of the training form).Abbreviations: QA, quality assurance; QP, qualified person; SAS, surface air system.
Mentions: The GMP staff is the crucial point of any good facility. Staff must have the necessary skills, be properly trained and always updated both in theory and in practice on the concept of quality assurance and standards of GMP. We planned an initial training and an ongoing training, as requested by the GMP guidelines (EudraLex – Vol 4, chapter 2)1 with frequent staff performance and training courses. At our facility, the training plan follows an annual schedule and it is differentiated by various topics for both production and QC staff: an example of training program is reported in Figure 2. In addition, special training schedules are set up for the technical, maintenance, and cleaning personnel. All the GMP staff duties, including the management staff and the QP, responsible for implementation and enforcement of GMP are specified in our job descriptions. Among the various activities of the initial training, microbiological validation of the operators is also crucial: only after successfully overcoming the microbial validation including aseptic gowning and operations also with media fill (as thereafter illustrated) the production staff is authorized to work in aseptic procedures. Moreover, the single operator involved in the production process is constantly monitored at the end of each work session. The personnel microbiological monitoring consists in testing the forearms as well as the five fingers. All the plates are incubated at 20°C–25°C for 5 days and then at 30°C–35°C for 5 days. The results are expressed as TAMC (total aerobic microbial count) and as UFC/plate (unit-forming colony) as requested by EuGMP/Annex1. Autochthon strains are tested in the validation of final product sterility testing. Every 3 months environmental microbiological, particulate, and staff data are collected in specific forms (Figure 3) in order to prepare our periodic reports (Trend Analysis). These trend analyses are built according to the theory of control of Shewhart charts, to fit the warning and alarm limits to the real situation of the production site. Adequate alarm and action limits have been established and are continuously updated to determine the immediate investigation and appropriate corrective action in case of deviations.

Bottom Line: In the 21st century scenario, new therapeutic tools are needed to take up the social and medical challenge posed by the more and more frequent degenerative disorders and by the aging of population.The recent category of advanced therapy medicinal products has been created to comprise cellular, gene therapy, and tissue engineered products, as a new class of drugs.Our hospital took up the challenge of this new path in the early 2000s; and herein we describe the approach we followed to set up a pharmaceutical-grade facility in a public hospital context, with the aim to share the solutions we found to make cell therapy compliant with the requirements for the production and the quality control of a high-standard medicinal product.

View Article: PubMed Central - PubMed

Affiliation: Cell Factory, Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.

ABSTRACT
In the 21st century scenario, new therapeutic tools are needed to take up the social and medical challenge posed by the more and more frequent degenerative disorders and by the aging of population. The recent category of advanced therapy medicinal products has been created to comprise cellular, gene therapy, and tissue engineered products, as a new class of drugs. Their manufacture requires the same pharmaceutical framework as for conventional drugs and this means that industrial, large-scale manufacturing process has to be adapted to the peculiar characteristics of cell-containing products. Our hospital took up the challenge of this new path in the early 2000s; and herein we describe the approach we followed to set up a pharmaceutical-grade facility in a public hospital context, with the aim to share the solutions we found to make cell therapy compliant with the requirements for the production and the quality control of a high-standard medicinal product.

No MeSH data available.


Related in: MedlinePlus