In the past decade, biotechnology, applied to pharmaceutic processes, have undergone multiple innovations, not always followed by changes, potentially resulting in signi cant improvements in e ciency. The constant evolution of disposables conquered a big parenthesis in this debate, claiming to lead to simpler operations, eliminating cleaning and sterilization steps, as well as their validation, thus reducing costs and time of operation per batch. This already resulted in concrete investments and realizations in the recent past. However, this process had not come without skepticism, mainly related to product quality. Assessed the goodness of the product from literature, the present thesis shall evaluate the bene ts of a full disposable plant (addressed as SU, single-use) for a monoclonal antibody production, following a generic model of exploitation of a mammalian cell (e.g. Chinese Hamster Ovary, CHO). The comparison with a common stainless-steel model (addressed as SS) will be conducted through a batch process simulation carried with SuperPro Designer ©. A canonical structure for the mAb plant has been followed. The main feature that need to be speci ed is the discontinuity nature of the process, except for some not-so-rare cases of semi continuous behavior, exploiting the perfusion technique. First eld of comparison is the schedule of the process. The focus is switched between plant level and section one, analyzing, for example, both maximum number of batches and equipment utilization factors. The software allows a graphical output to easily comprehend the issues and deal with con icts. Second eld of comparison is the economic one. Investment cost and operating cost are assessed, allowing a thorough evaluation. Both are discorporated and analyzed, subdivided into plant section components and di erent nature components, in order to be able to properly identify the reasons of the di erences. Third and last eld of comparison is the environmental one. A basic life cycle assessment has been carried out, comparing mainly the di erent impact generated by plastic waste (for the SU facility) and greater WFI utilization (for the SS one). The purpose of this elaborate, a part from the unique and not secondary results of this case study, is to highlight the importance of such simulation tools in every process early phase of development. Furthermore, revamping or general investment decision making through what-if analysis would become focused and legitimated.
Nello scorso decennio, la biotecnologia, applicata a processi farmaceutici, ha assistito a molte innovazioni, potenzialmente risultanti in incrementi di efficienza. La costante evoluzione dei disposable ha conquistato una importante parentesi nel dibattito, affermando di condurre ad operazioni più semplici, ad esempio eliminando procedure di lavaggio e sterilizzazione e relative validazioni, riducendo costi e tempi operativi per batch. Ciò ha portato a concreti investimenti nel recente passato. Ad ogni modo, questo mutamento è stato accolto con non poco scetticismo, nonostante la forte spinta da parte della letteratura, principalmente dovuto a preoccupazioni sull'intaccamento della qualità del prodotto. La tesi si propone di valutare la bontà di un impianto single-use per la produzione di anticorpi monoclonali, seguendo un modello generico di cellule mammifere. Il confronto con un comune impianto stainless steel verrà condotto attraverso un software di simulazione, SuperPro Designer ©, specializzato in processi discontinui. Primo ambito di confronto è la schedula di processo. L'analisi svarierà dal livello dell'impianto a quello delle singole sezioni, passando dal numero totale di batch annuo ai fattori di utilizzo delle unità. Il software garantisce un output grafico facile da comprendere, ottimo strumento per l'ottimizzazione. Secondo ambito di confronto è quello economico. Sono stati calcolati costi di investimento ed operativi, entrambi scissi e nuovamente analizzati, suddivisi per sezione o per natura, per garantire completezza e solidità, permettendo di identificare appropriatamente le ragioni delle differenze. Terzo ambito di confronto è l'impatto ambientale. Attraverso un basilare life cycle assessment, sono state comparate le principali differenze, generate dai rifiuti plastici da una parte, e dai maggior utilizzo di WFI dall'altra. Lo scopo dell'elaborato, a parte i risultati delle sezioni appena descritte, è quello di sottolineare l'importanza dei tool di simulazione ad ogni fase di sviluppo del progetto. Infatti, qualsiasi investimento, anche di revamping e ottimizzazione attraverso what-if analysis, migliorerebbe in ogni aspetto.
Modelling analysis and comparison between single-use system and stainless steel equipment in a biopharmaceutical manufacturing
AGAZZI, ALBERTO
2016/2017
Abstract
In the past decade, biotechnology, applied to pharmaceutic processes, have undergone multiple innovations, not always followed by changes, potentially resulting in signi cant improvements in e ciency. The constant evolution of disposables conquered a big parenthesis in this debate, claiming to lead to simpler operations, eliminating cleaning and sterilization steps, as well as their validation, thus reducing costs and time of operation per batch. This already resulted in concrete investments and realizations in the recent past. However, this process had not come without skepticism, mainly related to product quality. Assessed the goodness of the product from literature, the present thesis shall evaluate the bene ts of a full disposable plant (addressed as SU, single-use) for a monoclonal antibody production, following a generic model of exploitation of a mammalian cell (e.g. Chinese Hamster Ovary, CHO). The comparison with a common stainless-steel model (addressed as SS) will be conducted through a batch process simulation carried with SuperPro Designer ©. A canonical structure for the mAb plant has been followed. The main feature that need to be speci ed is the discontinuity nature of the process, except for some not-so-rare cases of semi continuous behavior, exploiting the perfusion technique. First eld of comparison is the schedule of the process. The focus is switched between plant level and section one, analyzing, for example, both maximum number of batches and equipment utilization factors. The software allows a graphical output to easily comprehend the issues and deal with con icts. Second eld of comparison is the economic one. Investment cost and operating cost are assessed, allowing a thorough evaluation. Both are discorporated and analyzed, subdivided into plant section components and di erent nature components, in order to be able to properly identify the reasons of the di erences. Third and last eld of comparison is the environmental one. A basic life cycle assessment has been carried out, comparing mainly the di erent impact generated by plastic waste (for the SU facility) and greater WFI utilization (for the SS one). The purpose of this elaborate, a part from the unique and not secondary results of this case study, is to highlight the importance of such simulation tools in every process early phase of development. Furthermore, revamping or general investment decision making through what-if analysis would become focused and legitimated.| File | Dimensione | Formato | |
|---|---|---|---|
|
2018_04_Agazzi.pdf
accessibile in internet per tutti
Descrizione: Thesis text
Dimensione
4.89 MB
Formato
Adobe PDF
|
4.89 MB | Adobe PDF | Visualizza/Apri |
I documenti in POLITesi sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
https://hdl.handle.net/10589/139613