Predictive models of lyophilization process for development, scale-up/tech transfer and manufacturing

Zhu, Tiejun; Moussa, Ehab M.; Witting, Madeleine; Zhou, Deliang; Sinha, Kushal; Hirth, Mario; Gastens, Martin H.; Shang, Sherwin; Nere, Nandkishor K.; Somashekar, Shubha Chetan; Alexeenko, Alina; Jameel, Feroz

doi:10.1016/j.ejpb.2018.05.005

Cited by 42 publications

(23 citation statements)

References 21 publications

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“…In an attempt to minimize the trial and error experiments, researchers have developed mathematical models for the determination of the optimum processing conditions based on the governing heat and mass transfer equations. 4,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] In these mathematical models, 2 input parameters, namely the overall vial heat transfer coefficient and the resistance to mass transfer of the dried product, are experimentally determined. The overall vial heat transfer coefficient is typically determined from a water sublimation test, whereas the resistance to mass transfer of the dried product is determined using the drug formulation.…”

Section: Introductionmentioning

confidence: 99%

An Experimental-Based Approach to Construct the Process Design Space of a Freeze-Drying Process: An Effective Tool to Design an Optimum and Robust Freeze-Drying Process for Pharmaceuticals

Assegehegn

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Franco

et al. 2020

Journal of Pharmaceutical Sciences

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The application of quality by design (QbD) is becoming an integral part of the formulation and process development for pharmaceutical products. An essential feature of the QbD philosophy is the design space. In this sense, a new approach to construct a process design space (PDS) for the primary drying section of a freeze-drying process is addressed in this paper. An effective customized design of experiments (DoE) is developed for freeze-drying experiments. The results obtained from the DoE are then used to construct the product-based PDS. The proposed product-based PDS construction approach has several advantages, including (1) eliminating assumptions on the heat transfer coefficient and dried product resistance, as it is constructed from experimental results specifically obtained from a given formulation, yielding more realistic and reliable results and (2) PDS construction based on a narrow range of product temperatures and considering the variations in product temperature and sublimation rate of vials across a shelf. This guarantees the effectiveness and robustness of the process and facilitates the process scale-up and transfer. The PDS developed herein was experimentally verified. The PDS predicted parameters were in excellent agreement with the experimentally obtained parameters.

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Section: Introductionmentioning

confidence: 99%

An Experimental-Based Approach to Construct the Process Design Space of a Freeze-Drying Process: An Effective Tool to Design an Optimum and Robust Freeze-Drying Process for Pharmaceuticals

Assegehegn

Fuente

Franco

et al. 2020

Journal of Pharmaceutical Sciences

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“…Some examples include a one‐dimensional model based lyophilization calculator 49 and a lyophilization process equipment capability map developed using an array of CFD simulations of various lyophilizers spanning multiple scales, as shown in Figure 18. Advances in lyophilization modeling at AbbVie were facilitated by collaboration with software vendors and academia 50,51 …”

Section: Lyophilization Process Equipment Modelingmentioning

confidence: 99%

Positioning for a sustainable future—Role of chemical engineers in transforming pharmaceutical process development

2021

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“…Even though this exercise was carried out retrospectively, it did highlight the importance of understanding the product, process, and equipment at all scales in order to have an efficient product development and technology transfer. A rational strategy (21,37,38) for technology transfer of the lyophilization process is to match the product temperature profile, where the lyophilization model can be extremely beneficial. This strategy requires the adjustment of the shelf temperature accordingly in response to the change in K v from laboratory to pilot and to commercial equipment.…”

Section: Case Studymentioning

confidence: 99%

Leveraging Lyophilization Modeling for Reliable Development, Scale-up and Technology Transfer

et al. 2019

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Modeling of the lyophilization process, based on the steady-state heat and mass transfer, is a useful tool in understanding and optimizing of the process, developing an operating design space following the quality-by-design principle, and justifying occasional process deviations during routine manufacturing. The steady-state model relies on two critical parameters, namely, the vial heat transfer coefficient, K v , and the cake resistance, R p . The classical gravimetric method used to measure K v is tedious, time-and resourceconsuming, and can be challenging and costly for commercial scale dryers. This study proposes a new approach to extract both K v and R p directly from an experimental run (e.g., temperature and Pirani profiles). The new methodology is demonstrated using 5% w/v mannitol model system. The values of K v obtained using this method are comparable to those measured using the classic gravimetric method. Application of the proposed approach to process scale-up and technology transfer is illustrated using a case study. The new approach makes the steady-state model a simple and reliable tool for model parameterization, thus maximizes its capability and is particularly beneficial for transfer products from lab/pilot to commercial manufacturing.

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Predictive models of lyophilization process for development, scale-up/tech transfer and manufacturing

Cited by 42 publications

References 21 publications

An Experimental-Based Approach to Construct the Process Design Space of a Freeze-Drying Process: An Effective Tool to Design an Optimum and Robust Freeze-Drying Process for Pharmaceuticals

An Experimental-Based Approach to Construct the Process Design Space of a Freeze-Drying Process: An Effective Tool to Design an Optimum and Robust Freeze-Drying Process for Pharmaceuticals

Positioning for a sustainable future—Role of chemical engineers in transforming pharmaceutical process development

Leveraging Lyophilization Modeling for Reliable Development, Scale-up and Technology Transfer

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