Abstract: In one general aspect, a method for filling multiple containers with a pharmaceutical product is disclosed, which comprises decontaminating sealed nested materials in a transfer chamber, removing from the sealed nested materials one or both of a container nest holding the multiple containers and a closure nest holding multiple closures, transferring from the transfer chamber to a controlled environment enclosure the removed nest, aseptically filling the containers with the pharmaceutical product, and closing the containers with the multiple closures. The nests are configured to allow multiple closures and containers to be simultaneously aligned concentrically, and closed simultaneously. Spring-loaded retaining structures on the closure nest allow it to releasably retain multiple closures above the corresponding multiple containers. In some embodiments the spring-loaded features are monolithically integrated with the closure nest.

Abstract: Systems and methods permit gloveless filling containers with a product. A filling arm is disposed within the chamber. An optical sensor is configured to locate and target openings of the containers within the chamber. Locations of the openings are used to guide the filling arm to fill the containers with a product.

Abstract: An apparatus and method are presented for removing container covers within a controlled environment enclosure without using gloves. The apparatus comprises an articulated arm apparatus and a gripping apparatus and can further comprise a controller. The articulated arm apparatus can be configurable for holding and moving a container in three dimensions; and the gripping apparatus can be configured for gripping a container cover sealing the container. The method comprises moving the container using the articulated arm apparatus while holding a gripping area of the container cover substantially stationary using the gripping apparatus. The apparatus can further comprise a sensor configured for supplying information to the controller for determining the location of the container cover gripping area and an orientation of the container cover. The method can further comprise inspecting the container cover using the sensor. The container can be moved along a path and within a space determined by the controller.

Abstract: The present invention involves a rotary peristaltic pump and associated method employing the relaxation of pressure on flexible tubing between the rotor and stator of the pump to restore the rotor to a start angle while a valve on the output of the pump is closed to avoid progress of fluid through the system. Three different implementations of the pump and method are presented including reciprocating the stator, reciprocating the rotor, and retracting the idler rollers of the rotor into the rotor to relieve the pressure on the flexible tubing. A controller ensures the appropriate switching and timing of the valve and rotor of the pump. The pump and associated method are directed to the precision dispensing of pharmaceutical fluids into containers, including containers held in container nests.

Abstract: A controlled environment enclosure comprises a robotic arm manipulation system used to protect and unprotect a fluid path and a swab within the controlled environment enclosure. The apparatus allows the fluid path to be protected against dangerous decontamination vapors and chemicals before the controlled environment enclosure is decontaminated. The apparatus allows the fluid path to be unprotected without the use of gloves or other means that degrade the integrity of the controlled environment enclosure when decontamination is completed. The apparatus and method allow for the protecting, unprotecting and decontaminating sequences to be automated. In some embodiments the fluid path comprises a fill needle that can removably and aseptically be sealed with a disposable monolithic injection moulded polymeric fill needle sheath.

Abstract: The present invention involves both an apparatus and an associated method for confirming the presence or absence of closures in a closure nest inside an aseptic chamber. The apparatus comprises a topographical profiler disposed to monitor the closure nests. Vertical displacements in topographical maps obtained by the profiler are compared with information from a database about the nest and closure combinations. Vertical displacements falling outside predetermined upper and lower bounds are deemed absences of closures. The topographical profiler may be disposed outside the aseptic chamber. The system may be automated via a controller and suitable software. In some embodiments the nests and disposed in the monitored area by robotic articulated arms. In other embodiments the closure nests are moved by vacuum pickup systems. The system and method may also be employed to assess the suitability of a closure nest for closing in an aseptic chamber containers in a container nest.

Abstract: An apparatus and method are presented for removing container covers within a controlled environment enclosure without using gloves. The apparatus comprises an articulated arm apparatus and a gripping apparatus and can further comprise a controller. The articulated arm apparatus can be configurable for holding and moving a container in three dimensions; and the gripping apparatus can be configured for gripping a container cover sealing the container. The method comprises moving the container using the articulated arm apparatus while holding a gripping area of the container cover substantially stationary using the gripping apparatus. The apparatus can further comprise a sensor configured for supplying information to the controller for determining the location of the container cover gripping area and an orientation of the container cover. The method can further comprise inspecting the container cover using the sensor. The container can be moved along a path and within a space determined by the controller.

Abstract: The system of the invention involves a gloveless aseptic processing system. The automated system is for filling nested pharmaceutical containers with a pharmaceutical fluid substance. A closed sterilizable gloveless isolator chamber is capable of maintaining an aseptic condition, having a sterilization system. The container filling system has a dispensing head for filling the containers, and a container closing system disposed within the gloveless isolator chamber with rams for pushing closures into openings of the nested containers. The container manipulation mechanism is disposed within the gloveless isolator chamber and is capable of positioning the nested pharmaceutical containers within the gloveless isolator chamber including operably disposing the nested pharmaceutical containers with the container filling system and the container closing system. Container tubs sealed by removable covers and contain a container nest bearing a plurality of pre-sterilized pharmaceutical containers.

Abstract: The present invention involves a fill needle system for aseptically dispensing a pharmaceutical fluid in an aseptic chamber comprises a fill needle tubing in fluid communication with a pharmaceutical fluid source via flexible tubing and extending through a fill needle hub; a fill needle dispensing tip disposed at a dispensing end of the fill needle tubing; a fill needle sheath shaped and arranged to removably mate with and seal aseptically to the fill needle hub to form an aseptically sealed volume enclosing the dispensing tip; and a fluid pressure pulse induction system disposed and configured to compress the flexible tubing in order to dislodge droplets of pharmaceutical fluid retained on the dispensing tip after halting dispensing of the pharmaceutical fluid. An associated method of dispensing pharmaceutical fluid comprises operating the fluid pressure pulse induction system to dislodge the droplets. The system may comprise a controller for automatically controlling the dispensing and droplet dislodging.

Abstract: Disclosed are systems and methods for aseptically filling pharmaceutical containers with a pharmaceutical substance and then lyophilizing it. In one general aspect, the system and method can employ a lyophilizer loader subsystem having an interior chamber in communication with an interior chamber of a lyophilizer subsystem via a portal with a sealable door, with the collective interior being aseptically sealable. An articulated robotic arm can be employed to batch transfer to the lyophilizer subsystem container nests bearing the pharmaceutical containers. In one embodiment, the nests may be transferred serially to the loader subsystem, with the articulated robotic arm being configured to transfer the nests of containers in batches to the lyophilizer subsystem. The articulated robotic arm can also be configured to be used to move batches of nests within the lyophilizer subsystem. One implementation includes two articulated arms and a joint rotary wrist driven by two rotary shoulders.

Abstract: Systems and methods for aseptically filling pharmaceutical containers with pharmaceutical fluid are disclosed. In one general aspect, these are based on an aseptically sealable chamber that includes a transfer wall to which pre-sealed pharmaceutical source and receiving containers are mounted aseptically. A robotic arm and a syringe store are disposed within the chamber along with a sterilizing facility for establishing in the chamber an aseptic condition. The robotic arm can grip and operate syringes to inject and/or extract pharmaceutical products from the containers by piercing their closures with the needles of the syringes.

Abstract: A system is presented for monitoring and controlling in a sterilizable environment the peeling of a cover from a tub sealed by the cover. The system employs a platform having a fiducial source locating structure for holding the tub, a cover removal station disposed to engage with the cover and to peel the cover from the tub, a light source disposed to illuminate a portion of the platform proximate the cover removal station, a light sensor sensitive to light from the light source and disposed to preferentially collect and measure light diffusely reflected from the illuminated portion of the platform, and a controller with software to operate the system. An associated method for monitoring and controlling the peeling of the cover involves moving a peeled portion of the cover into a predetermined peeling monitor zone within the illuminated portion of the platform, and measuring an intensity of light from the light source diffusely reflected specifically from the peeling monitor zone.

Abstract: In one general aspect, a method for filling multiple containers with a pharmaceutical product is disclosed, which comprises decontaminating sealed nested materials in a transfer chamber, removing from the sealed nested materials one or both of a container nest holding the multiple containers and a closure nest holding multiple closures, transferring from the transfer chamber to a controlled environment enclosure the removed nest, aseptically filling the containers with the pharmaceutical product, and closing the containers with the multiple closures. The nests are configured to allow multiple closures and containers to be simultaneously aligned concentrically, and closed simultaneously. Spring-loaded retaining structures on the closure nest allow it to releasably retain multiple closures above the corresponding multiple containers. In some embodiments the spring-loaded features are monolithically integrated with the closure nest.

Abstract: The present invention involves a rotary peristaltic pump and associated method employing the relaxation of pressure on flexible tubing between the rotor and stator of the pump to restore the rotor to a start angle while a valve on the output of the pump is closed to avoid progress of fluid through the system. Three different implementations of the pump and method are presented including reciprocating the stator, reciprocating the rotor, and retracting the idler rollers of the rotor into the rotor to relieve the pressure on the flexible tubing. A controller ensures the appropriate switching and timing of the valve and rotor of the pump. The pump and associated method are directed to the precision dispensing of pharmaceutical fluids into containers, including containers held in container nests.

Abstract: A controlled environment enclosure comprises a robotic arm manipulation system used to protect and unprotect a fluid path and a swab within the controlled environment enclosure. The apparatus allows the fluid path to be protected against dangerous decontamination vapors and chemicals before the controlled environment enclosure is decontaminated. The apparatus allows the fluid path to be unprotected without the use of gloves or other means that degrade the integrity of the controlled environment enclosure when decontamination is completed. The apparatus and method allow for the protecting, unprotecting and decontaminating sequences to be automated. In some embodiments the fluid path comprises a fill needle that can removably and aseptically be sealed with a disposable monolithic injection moulded polymeric fill needle sheath.

Abstract: A hermetically sealed multi-axis articulated arm apparatus for use within a sealable isolator chamber is disclosed. In one general aspect, it comprises a rotational shaft that passes through an opening in the chamber, a sealing member disposed within the chamber for sealing the shaft to an inner surface of the chamber, interconnected hermetically sealed arm segments operably attached to the linear motion shaft; an end effector operably attached to a terminal arm segment among the arm segments, and at least one fully enclosed drive system for driving and controlling the shaft and the arm segments. The rotational shaft can further be a linear motion shaft for which the sealing member is a bellows. The materials for the parts of the apparatus exposed to the atmosphere of the chamber can be compatible with an aseptic and cleanable environment and the surfaces of the arm segments can be shaped to avoid pooling of contaminants.

Abstract: Disclosed are systems and methods for aseptically filling pharmaceutical containers with a pharmaceutical substance and then lyophilizing it. In one general aspect, the system and method can employ a lyophilizer loader subsystem having an interior chamber in communication with an interior chamber of a lyophilizer subsystem via a portal with a sealable door, with the collective interior being aseptically sealable. An articulated robotic arm can be employed to batch transfer to the lyophilizer subsystem container nests bearing the pharmaceutical containers. In one embodiment, the nests may be transferred serially to the loader subsystem, with the articulated robotic arm being configured to transfer the nests of containers in batches to the lyophilizer subsystem. The articulated robotic arm can also be configured to be used to move batches of nests within the lyophilizer subsystem. One implementation includes two articulated arms and a joint rotary wrist driven by two rotary shoulders.

Abstract: The present invention involves a rotary peristaltic pump and associated method employing the relaxation of pressure on flexible tubing between the rotor and stator of the pump to restore the rotor to a start angle while a valve on the output of the pump is closed to avoid progress of fluid through the system. Three different implementations of the pump and method are presented including reciprocating the stator, reciprocating the rotor, and retracting the idler rollers of the rotor into the rotor to relieve the pressure on the flexible tubing. A controller ensures the appropriate switching and timing of the valve and rotor of the pump. The pump and associated method are directed to the precision dispensing of pharmaceutical fluids into containers, including containers held in container nests.

Abstract: A purgeable fill needle for dispensing pharmaceutical fluid into a pharmaceutical container comprises a fill needle hub, a fill needle tubing extending through the fill needle hub; a fill needle dispensing tip; a fill needle sheath removably mated with and seal aseptically to the fill needle hub to form an aseptically sealed volume enclosing the dispensing tip; and a terminal fluid ejector for removing fluid retained by the tip after halting dispensing of pharmaceutical fluid. The terminal fluid ejector may be based on automatic injection of an aseptic gas into the fill needle tubing, automated action of a gas bladder at the dispensing tip, or the automated operation of a compression actuator at the dispensing tip. The removal of terminal fluid retained at the tip after halting dispensing of the fluid may also be effected by automatically blowing attached droplets off the tip and automatically shaking the fill needle tubing.

Abstract: Systems and methods for aseptically filling pharmaceutical containers with pharmaceutical fluid are disclosed. In one general aspect, these are based on an aseptically sealable chamber that includes a transfer wall to which pre-sealed pharmaceutical source and receiving containers are mounted aseptically. A robotic arm and a syringe store are disposed within the chamber along with a sterilizing facility for establishing in the chamber an aseptic condition. The robotic arm can grip and operate syringes to inject and/or extract pharmaceutical products from the containers by piercing their closures with the needles of the syringes.