Flexible Manufacturing: The Future State of Drug Product Development and Commercialization in the Pharmaceutical Industry

Kapoor, Yash; Meyer, Robert; Meyer, Brian K.; DiNunzio, James; Bhambhani, Akhilesh; Stanbro, Justin; Ploeger, Kristin J. M.; Guidry, Erin N.; Troup, Gregory M.; Procopio, Adam; Templeton, Allen C.

doi:10.1007/s12247-019-09426-z

Cited by 19 publications

(15 citation statements)

References 13 publications

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“…Continuous processing is already used in the chemical and pharmaceutical industry to run flexible and cost-effective processes and will ultimately offer on demand production. Additionally, the process integration made possible by continuous manufacturing may also reduce operation time and facilitate automation and process analytical technologies (PAT), which can result in a higher productivity and higher product quality [111] , [112] . The relative simplicity of mRNA manufacturing makes the process well suited for continuous processing, and in particular at a microfluidic scale ( Fig.…”

Section: Mrna Manufacturing: From Upstream To Downstreammentioning

confidence: 99%

mRNA vaccines manufacturing: Challenges and bottlenecks

Rosa

Prazeres

Azevedo

et al. 2021

Vaccine

281

255

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Vaccines are one of the most important tools in public health and play an important role in infectious diseases control. Owing to its precision, safe profile and flexible manufacturing, mRNA vaccines are reaching the stoplight as a new alternative to conventional vaccines. In fact, mRNA vaccines were the technology of choice for many companies to combat the Covid-19 pandemic, and it was the first technology to be approved in both United States and in Europe Union as a prophylactic treatment. Additionally, mRNA vaccines are being studied in the clinic to treat a number of diseases including cancer, HIV, influenza and even genetic disorders. The increased demand for mRNA vaccines requires a technology platform and cost-effective manufacturing process with a well-defined product characterisation. Large scale production of mRNA vaccines consists in a 1 or 2-step in vitro reaction followed by a purification platform with multiple steps that can include Dnase digestion, precipitation, chromatography or tangential flow filtration. In this review we describe the current state-of-art of mRNA vaccines, focusing on the challenges and bottlenecks of manufacturing that need to be addressed to turn this new vaccination technology into an effective, fast and cost-effective response to emerging health crises.

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Section: Mrna Manufacturing: From Upstream To Downstreammentioning

confidence: 99%

mRNA vaccines manufacturing: Challenges and bottlenecks

Rosa

Prazeres

Azevedo

et al. 2021

Vaccine

281

255

View full text Add to dashboard Cite

show abstract

“…The combination of multi-day drying cycles, scale-up challenges (especially with multiple units), and turnaround time for cleaning and sterilization can result in lyophilization process being the critical supply bottleneck, especially for products with variable market demand, short order lead times, and/or high volume needs to respond to outbreaks. Now in the twenty-first century, various companies are actively pursuing alternatives to traditional freeze-drying in a vial so that processes can be modular, flexible, and "scaledout" instead of "scaled-up" to meet diverse patient populations and different modalities, including small molecule, peptide, therapeutic protein, or vaccine (6). Unit operations of the future that rely on different heat transfer mechanisms to reduce cycle time (microwave drying, infrared drying, vacuum drying, spray drying) (7)(8)(9)(10) or drying outside of the vial (spray drying, bulk drying, filter drying, etc.)…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Microwave Vacuum Drying as an Alternative to Freeze-Drying of Biologics and Vaccines: the Power of Simple Modeling to Identify a Mechanism for Faster Drying Times Achieved with Microwave

Bhambhani¹,

Stanbro²,

Roth³

et al. 2021

AAPS PharmSciTech

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Vial-based lyophilization for biopharmaceuticals has been an indispensable cornerstone process for over 50 years. However, the process is not without significant challenges. Capital costs to realize a lyophilized drug product facility, for example, are very high. Similarly, heat and mass transfer limitations inherent in lyophilization result in drying cycle on the order of several days while putting practical constraints on available formulation space, such as solute mass percentage or fill volume in a vial. Through collaboration with an external partner, we are exploring microwave vacuum drying (MVD) as a faster drying process to vial lyophilization wherein the heat transfer process occurs by microwave radiation instead of pure conduction from the vial. Drying using this radiative process demonstrates greater than 80% reduction in drying time over traditional freeze-drying times while maintaining product activity and stability. Such reduction in freeze-drying process times from days to several hours is a welcome change as it enables flexible manufacturing by being able to better react to changes either in terms of product volume for on-demand manufacturing scenarios or facilities for production (e.g., scale-out over scale-up). Additionally, by utilizing first-principle modeling coupled with experimental verification, a mechanism for faster drying times associated with MVD is proposed in this article. This research, to the best of our knowledge, forms the very first report of utilizing microwave vacuum drying for vaccines while utilizing the power of simplified models to understand drying principles associated with MVD.

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“…Although flexible manufacturing is not a new paradigm, there has been growing interest in recent years due to factors including the growing demand for customised products, shorter product life cycles and environmental impact [23,29,60]. Compared to traditional transfer lines that enable high volume but less flexibility in their design, FMS allow for reaction to volume fluctuations, mixed batch production and multiple product types within the same product family [9].…”

Section: Related Workmentioning

confidence: 99%

Process Monitoring in a Flexible Manufacturing Cell through Data Analytics and a Visualisation Tool

Arellano

Nguyen

Hinton

et al. 2021

Preprint

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With the need of more responsive and resilient manufacturing processes for high value, customised products, Flexible Manufacturing Systems (FMS) remain a very relevant manufacturing approach. Due to their complexity, quality monitoring in these types of systems can be very difficult, particularly in those scenarios where the monitoring cannot be fully automated due to functional, safety and legal characteristics. In these scenarios, quality practitioners concentrate on monitoring the most critical processes and leaving out the inspection of those that are still meeting quality requirements but showing signs of future failure. In this paper we introduce a methodology and visualisation tool based on data analytics that allows the practitioner to anticipate out of control processes and take action. By identifying a reference model or best performing machine, and the occurring patterns in the quality data, the presented approach identifies the adjustable processes that are still in control, allowing the practitioner to decide if any changes in the machine's settings are needed (tool replacement, repositioning the axis, etc). An initial deployment of the tool at BMW Plant Hams Hall to monitor a focussed set of part types and features has shown a reduction in scrap of 97% throughout 2020 in relation to the monitored features compared to the previous year. This in the long run will reduce reaction time in following quality control procedure, reduce significant scrap costs and ultimately reduce the need for measurements and enable more output in terms of volume capacity.

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Flexible Manufacturing: The Future State of Drug Product Development and Commercialization in the Pharmaceutical Industry

Cited by 19 publications

References 13 publications

mRNA vaccines manufacturing: Challenges and bottlenecks

mRNA vaccines manufacturing: Challenges and bottlenecks

Evaluation of Microwave Vacuum Drying as an Alternative to Freeze-Drying of Biologics and Vaccines: the Power of Simple Modeling to Identify a Mechanism for Faster Drying Times Achieved with Microwave

Process Monitoring in a Flexible Manufacturing Cell through Data Analytics and a Visualisation Tool

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