The Effect of Dryer Load on Freeze Drying Process Design

Patel, Sajal M.; Jameel, Feroz; Pikal, Michael J.

doi:10.1002/jps.22132

Cited by 45 publications

(26 citation statements)

References 14 publications

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“…One would expect a small condenser pressure increase with low sublimation loads, such as products being dried at low temperature, such as sucrose formulations, and particularly with partial loads. The rise in condenser pressure is more clearly defined with a full load (i.e., all shelves loaded fully) compared to partial load (one third of full load used in this study) (16). Also, it is important to note that there was ∼25% residual water at the offset of product thermocouple response.…”

Section: Residual Water Analysismentioning

confidence: 89%

“…However, TDLAS is an expensive technique which is not a common accessory with freeze-dryers, and the offset of dew point is sometimes difficult to determine as it reaches the plateau value asymptotically. From a sterility standpoint, it is best to avoid use of thermocouples in the product vials in manufacturing, and furthermore, vials monitored with thermocouples are not representative of the entire batch, with the bias becoming much more serious in manufacturing (16). Thus, thermocouples are not suitable for evaluating the end point of primary drying in manufacturing.…”

Section: Comparison Of the Techniquesmentioning

confidence: 99%

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Determination of End Point of Primary Drying in Freeze-Drying Process Control

2010

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Abstract. Freeze-drying is a relatively expensive process requiring long processing time, and hence one of the key objectives during freeze-drying process development is to minimize the primary drying time, which is the longest of the three steps in freeze-drying. However, increasing the shelf temperature into secondary drying before all of the ice is removed from the product will likely cause collapse or eutectic melt. Thus, from product quality as well as process economics standpoint, it is very critical to detect the end of primary drying. Experiments were conducted with 5% mannitol and 5% sucrose as model systems. The apparent end point of primary drying was determined by comparative pressure measurement (i.e., Pirani vs. MKS Baratron), dew point, Lyotrack (gas plasma spectroscopy), water concentration from tunable diode laser absorption spectroscopy, condenser pressure, pressure rise test (manometric temperature measurement or variations of this method), and product thermocouples. Vials were pulled out from the drying chamber using a sample thief during late primary and early secondary drying to determine percent residual moisture either gravimetrically or by Karl Fischer, and the cake structure was determined visually for melt-back, collapse, and retention of cake structure at the apparent end point of primary drying (i.e., onset, midpoint, and offset). By far, the Pirani is the best choice of the methods tested for evaluation of the end point of primary drying. Also, it is a batch technique, which is cheap, steam sterilizable, and easy to install without requiring any modification to the existing dryer.

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Section: Residual Water Analysismentioning

confidence: 89%

Section: Comparison Of the Techniquesmentioning

confidence: 99%

Determination of End Point of Primary Drying in Freeze-Drying Process Control

2010

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“…Compared with a full load, demand for heat would be significantly less for a partially loaded dryer and consequently shelf surface temperature will be higher [30]. This would lead to a shorter primary drying time for a partial loaded dryer.…”

Section: Dryer Loadmentioning

confidence: 96%

Lyophilization of Therapeutic Proteins in Vials: Process Scale-Up and Advances in Quality by Design

Wang

McCoy²,

Pikal

et al. 2015

Lyophilized Biologics and Vaccines

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“…The effect of load condition on critical process parameters, such as product temperature and drying time, on a lab scale, pilot scale, and a clinical scale dryer has been recently investigated (8). In going from full load to partial load condition, drying time decreased and product temperature increased.…”

Section: Effect Of Load On Freeze-drying Process Designmentioning

confidence: 99%

Emerging Freeze-Drying Process Development and Scale-up Issues

Patel¹,

Pikal

2011

AAPS PharmSciTech

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Abstract. Although several guidelines do exist for freeze-drying process development and scale-up, there are still a number of issues that require additional attention. The objective of this review article is to discuss some emerging process development and scale-up issue with emphasis on effect of load condition and freeze-drying in novel container systems such as syringes, Lyoguard trays, ampoules, and 96-well plates. Understanding the heat and mass transfer under different load conditions and for freeze-drying in these novel container systems will help in developing a robust freeze-drying process which is also easier to scale-up. Further research and development needs in these emerging areas have also been addressed.

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The Effect of Dryer Load on Freeze Drying Process Design

Cited by 45 publications

References 14 publications

Determination of End Point of Primary Drying in Freeze-Drying Process Control

Determination of End Point of Primary Drying in Freeze-Drying Process Control

Lyophilization of Therapeutic Proteins in Vials: Process Scale-Up and Advances in Quality by Design

Emerging Freeze-Drying Process Development and Scale-up Issues

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