Process monitoring and control using battery-free multipoint wireless product condition sensing

Abstract

An arrangement for monitoring an aseptic manufacturing process includes product condition sensors capable of making closely spaced measurements of a product condition such as temperature or humidity. The measurements are made using closely spaced sensors arranged in a linear array on a single probe, which may be used to take measurements at multiple levels within the product. Data from the sensors is transmitted to a data collection point via short range wireless digital communications. The sensors may be used to measure temperature and humidity at a single point. For example, when the sensors are used in pharmaceutical freeze drying, the location of a sublimation front may be calculated for each vial, and the freeze drying process may be controlled using the data.

1 . A product condition measurement unit for measuring a condition profile of a product contained in a product vial being processed in an aseptic pharmaceutical processing chamber, comprising:
 a support structure for positioning in an opening of the product vial;   a single elongate probe supported by the support structure and having a plurality of sensors spaced longitudinally in a linear array along the single elongate probe at incremental distances from the support structure, the plurality of sensors comprising surface mount sensors mounted on a printed circuit board;   a processor supported by the support structure and connected for receiving measurements from the plurality of sensors.   
     
     
         2 . The product condition measurement unit of  claim 1 , further comprising:
 a radio frequency energy harvesting board connected for powering the processor using a received wireless powering signal.   
     
     
         3 . The product condition measurement unit of  claim 1 , wherein the condition profile comprises a temperature profile. 
     
     
         4 . The product condition measurement unit of  claim 1 , wherein the condition profile comprises a humidity profile. 
     
     
         5 . The product condition measurement unit of  claim 1 , further comprising a measurement processing module configured to convert each one of the measurements to both a temperature measurement and a humidity measurement at a single location in space. 
     
     
         6 . The product condition measurement unit of  claim 1 , wherein the surface mount sensors comprise ceramic surface mount capacitive sensors. 
     
     
         7 . The product condition measurement unit of  claim 1 , wherein the processor is mounted on the printed circuit board. 
     
     
         8 . The product condition measurement unit of  claim 1 , further comprising:
 a radio transmitter for transmitting measurement data via a local wireless network.   
     
     
         9 . The product condition measurement unit of  claim 8 , wherein the processor is configured to transmit a unique ID code of the product condition measurement unit via the local wireless network. 
     
     
         10 . The product condition measurement unit of  claim 8 , further comprising:
 a communications antenna connected to the processor to transmit the measurement data via the local wireless network.   
     
     
         11 . The product condition measurement unit of  claim 1 , wherein the sensors are spaced less than 2 mm from adjacent sensors along the single elongate probe. 
     
     
         12 . The product condition measurement unit of  claim 1 , wherein the plurality of sensors comprises more than  6  sensors. 
     
     
         13 . A method for freeze drying a product containing a frozen solvent, the product being in a plurality of vials having vial openings and arranged in a freeze drying chamber, the method comprising:
 subjecting the product to process conditions causing sublimation of the frozen solvent;   in a vial of the plurality of vials, while the product is subjected to the process conditions, measuring a location of a sublimation front using a linear array of product condition sensors arranged along a single elongate measurement probe extending into the product, the array having a pitch of less than 2 mm, the linear array of product condition sensors comprising surface mount sensors mounted on a printed circuit board; and   controlling the process conditions based on the measured location of sublimation front.   
     
     
         14 . The method of the preceding claim, further comprising:
 returning the product to ambient conditions; and   in the vial, while the product is subjected to the ambient conditions, measuring a humidity profile of the product using the linear array of product condition sensors.   
     
     
         15 . The method of  claim 13 , wherein the plurality of product vials is arranged on a plurality of shelves, each individual shelf having an individual adjustable heat transfer system for transferring heat from the shelf to vials supported by the shelf, and wherein controlling the process conditions based on the measured locations of the sublimation fronts further comprises:
 regulating an adjustable heat transfer system of a particular shelf on which the vial is located based on the measured location of the sublimation front.   
     
     
         16 . The method of  claim 13 , further comprising:
 powering a product condition measurement unit on the vial using a wireless radio frequency powering signal.   
     
     
         17 . The method of  claim 13 , further comprising:
 transmitting measurement data by a wireless communications transmitter on the vial.   
     
     
         18 . The method of  claim 13 , wherein the product condition sensors are temperature sensors, the method further comprising:
 determining the location of the sublimation front by estimating a product temperature gradient based on temperature measurements of the product.   
     
     
         19 . The method of  claim 13 , further comprising:
 estimating a propagation velocity of the sublimation front based on repeated measurements.   
     
     
         20 . An aseptic pharmaceutical processing system, comprising:
 an aseptic enclosure for aseptically isolating an interior of the enclosure from ambient atmosphere;   environmental control apparatus connected for controlling conditions in the interior of the aseptic enclosure; and   at least one measurement unit positioned to measure temperature and humidity in the interior of the aseptic enclosure and connected for providing measurements to the environmental control apparatus, the at least one measurement unit comprising a sensor and processor for measuring both temperature and humidity at a single location in space.   
     
     
         21 . The aseptic pharmaceutical processing system of the preceding claim, wherein the sensor is a capacitive sensor. 
     
     
         22 . The aseptic pharmaceutical processing system of  claim 20 , wherein the at least one measurement unit comprises a plurality of sensors arranged on a printed circuit board. 
     
     
         23 . The aseptic pharmaceutical processing system of the preceding claim, wherein the plurality of sensors are arranged to measure profiles of temperature and humidity within a product being processed within the aseptic enclosure. 
     
     
         24 . The aseptic pharmaceutical processing system of  claim 22 , wherein the plurality of sensors are arranged to measure environmental conditions within the aseptic enclosure by averaging measurements from the plurality of sensors.