Patent Description:
The invention relates to methods and systems for loading pharmaceutical containers into a lyophilization system.

Lyophilization, also referred to as freeze-drying, is employed in the field of medical technology to increase the shelf life of products such as vaccines and other injectables. By removing the water from the material and sealing the material in a vial or other container, the material can be easily stored, shipped, and later reconstituted to its original form for injection. Lyophilization is also employed to produce tablets or wafers, the advantage of which is less excipient as well as a rapidly absorbed and easily administered dosage form.

In prior art pharmaceutical container loading arrangements, the pharmaceutical containers are typically loaded sequentially into the lyophilizer. To this end, conveyor belt systems are often employed, and the containers are entrained one behind the other for transfer to the lyophilizer.

<CIT> relates to a frog-leg-arm robot for transferring an object to be conveyed, with the object placed on a hand unit, and also to a control method thereof.

In a first aspect, an integrated pharmaceutical processing system is presented comprising: a lyophilizing subsystem configured to lyophilize a pharmaceutical substance and having a lyophilizer interior chamber sealable from an ambient environment and a supply portal with a sealable door; and a lyophilizer loading subsystem having a loader interior chamber sealable from the ambient environment and in communication with the lyophilizer interior via the supply portal, the loading subsystem comprising within the loader interior chamber: a multi-nest support mechanism that includes a plurality of support structures that are each constructed to support one of a plurality of multi-container nests, and having a range of motion that extends between a nest loading station and a first location in the lyophilizer interior chamber, and a drive mechanism operatively connected to the multi-nest support mechanism and operative to drive the multi-nest support mechanism between the loading station and the first location in the lyophilizer interior chamber.

The multi-nest support mechanism may be configured to receive the plurality of container nests in series before transferring them in parallel. The multi-nest support mechanism may comprise an articulated robotic arm configured to engage simultaneously with the plurality of container nests and to place them via the supply portal at a first location in the lyophilizer interior chamber. The articulated robotic arm may be configured to move the plurality of container nests from the first location to a second location in the lyophilizer interior chamber. The articulated robotic arm may comprise a rotary end effector disposed at a distal end of the arm, wherein the rotary end effector includes the multi-nest support mechanism on a first side and a pushing surface on a second side.

The articulated robotic arm may further comprise a plurality of rotary joints all configured to rotate about parallel vertical rotary axes. The articulated robotic arm may further comprise two rotary shoulders disposed at a proximal end of the articulated robotic arm, two rotary elbows, and a joint rotary wrist disposed at a distal end of the articulated robotic arm, wherein articulation of the arm is driven by the two rotary shoulders. The articulated robotic arm may be configured to allow the joint rotary wrist to pass between the rotary elbows to a position proximate a nest access location within the loader interior chamber.

The system may further comprise a pharmaceutical filling subsystem having a filling system interior chamber sealable from the ambient environment and comprising a filling station within the filling system interior chamber configured to fill with the pharmaceutical compound pharmaceutical containers held in the container nests. The system may further comprise an accumulator subsystem having an accumulator interior chamber sealable from the ambient environment and in communication with the loader interior chamber and the filling system interior chamber, the accumulator subsystem being configured to accumulate within the accumulator interior chamber from the filling subsystem container nests bearing containers at least partially filled with the pharmaceutical compound and to make the container nests available to the lyophilizer loading subsystem.

In a further aspect, a method is presented for aseptically processing a pharmaceutical substance, the method comprising: at least partially filling with the pharmaceutical substance under an aseptic condition within a sealed processing chamber a plurality of containers held in each of a plurality of container nests; batch transferring to a lyophilizer a plurality of the container nests bearing containers containing the pharmaceutical substance, and operating the lyophilizer to lyophilize the pharmaceutical substance.

The method may further include sealing an interior chamber of the integrated pharmaceutical processing system against an external environment; establishing in the interior chamber of the pharmaceutical processing system an aseptic condition before the step of at least partially filling; and wherein the step of batch transferring includes batch relocating the plurality of container nests with their pharmaceutical containers to an interior chamber of the lyophilizer without unsealing the integrated pharmaceutical processing system; and sealing an interior chamber of the lyophilizer from a remainder of the integrated pharmaceutical processing system before the step of operating the lyophilizer. The relocating may comprise operating an articulated robotic arm to engage with the plurality of container nests; and operating the articulated robotic arm to place the plurality of container nests at a first location in the interior chamber of the lyophilizer.

The method may further comprise operating the articulated robotic arm to move the plurality of nests from the first location in the interior chamber of the lyophilizer to a second location in the interior chamber of the lyophilizer. The method may further comprise serially transferring within the processing system from the filling station to an interior chamber of an accumulator subsystem a plurality of container nests bearing containers containing the pharmaceutical substance; and serially transferring within the interior chamber of processing system the plurality of nests from the interior chamber of the accumulator subsystem to a nest access location in an interior chamber of a lyophilizer loading subsystem. The steps of filling and batch transferring may operate simultaneously on different container nests.

In a further aspect, an integrated pharmaceutical processing system is presented comprising an actuator assembly including: a housing having first and second shaft openings; at least one rotary actuator held in the housing; a first output shaft that passes through the first shaft opening in the housing, has a first end responsive to the at least one rotary actuator inside the housing, and has a second end outside the housing; a second output shaft located proximate that first output shaft, wherein the second output shaft passes through the second shaft opening in the housing, has a first end responsive to the at least one rotary actuator inside the housing, and has a second end outside the housing; a first upper arm having a first end connected to the second end of the first shaft and a having a second end so that it is at least generally perpendicular to an axis of rotation of the first shaft; a second upper arm having a first end connected to the second end of the second shaft and having a second end so that it is at least generally perpendicular to an axis of rotation of the second shaft; a first forearm having a first end and a second end; a second forearm having a first end and a second end; a first articulation between the second end of the first upper arm and the first end of the first forearm; a second articulation between the second end of the second upper arm and the first end of the second forearm; a wrist member including: an articulation mount having an axis of rotation; at least one nest support structure to support a multi-container nest on one side of the axis of rotation of the articulation mount; a pushing surface located opposite the axis of rotation of the articulation mount from the nest support structure and is at least generally parallel to the axis of rotation of the articulation mount; a third articulation between the second end of the first forearm and the second end of the second forearm, wherein the axes of rotation of the first and second output shafts, and the axes of the first, second, and third articulations are at least generally parallel to define a five-bar linkage, and a rotary wrist actuator between the third articulation and the wrist member articulation mount.

The housing, housing openings, wrist actuator, and the first, second, and third articulations may all be sealed. The nest support structure may be a multi-nest support mechanism of support structures that are each constructed to support one of a plurality of multi-container nests. The integrated pharmaceutical processing system may be a lyophilizer loading system. The first and second forearms may be offset with respect to each other in the direction of the axes of rotation to allow them to pass next to each other and above the first and second output shafts. The apparatus may further include a lifting actuator operatively connected to the first and second output shafts to lift the nests during transfers.

Systems according to the invention can have the advantage that they load contaner nests in parallel instead of in series. This can help prevent issues that can occur in prior art systems in which an entrainment error of a single container can halt the lyophilization process, or at least require intervention in some way or other. This can fundamentally improve the throughput of the system and thereby the costs associated with the process. At the root of this matter lies the fact that such prior art solutions can be fundamentally serial systems.

The above mentioned and other features and objects of this invention, and the manner of attaining them, will become more apparent and the invention itself will be better understood by reference to the following description of an embodiment of the invention taken in conjunction with the accompanying drawings, wherein:.

Corresponding reference characters indicate corresponding parts throughout the several views. Although the drawings represent embodiments of the present invention, the drawings are not necessarily to scale and certain features may be exaggerated in order to better illustrate and explain the present invention. The flow charts and screen shots are also representative in nature, and actual embodiments of the invention may include further features or steps not shown in the drawings. The exemplification set out herein illustrates an embodiment of the invention, in one form, and such exemplifications are not to be construed as limiting the scope of the invention in any manner, wherein the scope of the invention to which this European patent relates is defined by the appended claims.

The embodiments disclosed below are not intended to be exhaustive or limit the invention to the precise form disclosed in the following detailed description. Rather, the embodiments are chosen and described so that others skilled in the art may utilize their teachings.

The present invention relates to a system and method for filing pharmaceutical containers with a pharmaceutical substance or other material to be lyophilized, accumulating the filled containers, and loading the filled containers into a lyophilization system. Whereas prior art systems typically serially entrain the containers and then transfer them one at a time serially to the lyophilizer, the present specification will describe below a system and method for handling the containers within nests which allow the several containers within the nests to be transferred simultaneously. At least one arrangement for such simultaneous transfer will be described, based on an articulated robotic arm system. As will be shown, the system allows for a plurality of nests of containers to be transferred simultaneously to the lyophilizer.

In the present specification, the term "pharmaceutical substance" is used to describe materials of organic or inorganic nature employed in the medical field.

<FIG> shows a plan view schematic diagram of a pharmaceutical processing system <NUM> for filing pharmaceutical containers with a pharmaceutical material, accumulating the filled containers, and loading the filled containers into a lyophilization system. System <NUM> comprises a pharmaceutical container loading subsystem <NUM>, a lyophilizer subsystem <NUM>, an accumulator subsystem <NUM>, and a pharmaceutical container filling subsystem <NUM>. Tunnels <NUM>, <NUM>, and <NUM> join respectively the lyophilizer subsystem <NUM> to the loading subsystem <NUM>, the loading subsystem <NUM> to the accumulator subsystem <NUM>, and the accumulator subsystem <NUM> to the filling subsystem <NUM>. An environmental condition is established in loading subsystem <NUM> and is maintained by means of the tunnels <NUM>, <NUM>, and <NUM> throughout accumulator subsystem <NUM> and loading subsystem <NUM>. Since lyophilizer subsystem <NUM> has to maintain a unique environmental condition different from that in the rest of system <NUM>, lyophilizer subsystem <NUM> may be sealed off from the rest of system <NUM> by means of a suitable door, as shown later in <FIG>. Tunnel <NUM> nevertheless maintains the environmental condition of the rest of the system up to that door.

<FIG> shows a more detailed plan view of tunnel <NUM>, loader subsystem <NUM>, tunnel <NUM>, and lyophilizer subsystem <NUM>. Loader subsystem <NUM> comprises articulated robotic arm subsystem <NUM> for batch transferring container bearing nests into lyophilizer subsystem <NUM> through tunnel <NUM>, at least one container nest pedestal <NUM> (four are shown in <FIG>), and a transfer articulated robotic arm <NUM> for transferring container nests <NUM> serially from a source location in tunnel <NUM> to the at least one container nest pedestal <NUM>. In the present specification, we use the term "container nest access location" to describe a generalized location from which the robotic arm <NUM> may access a plurality of container nests <NUM>, including for example without limitation the set of pedestals <NUM>. The arrangement shown in <FIG> allows for the serial transfer of container nests <NUM> from accumulator subsystem <NUM> to lyophilizer loader subsystem <NUM>, articulated robotic arm <NUM> being configured for serially transferring container nests <NUM>. In other embodiments, a different means may be employed for the transfer of container nests <NUM> from accumulator subsystem <NUM> to lyophilizer loader subsystem <NUM>, and such arrangements may allow the batch transfer of container nests <NUM>. Other arrangements for container nest access locations may be employed. Articulated robotic arm subsystem <NUM> is disposed to engage with one or more container bearing nests on the at least one container nest pedestal <NUM> and to transfer the nests to the lyophilizer subsystem <NUM>.

The term "batch relocating" or "batch transferring" is used in this specification to refer to a number of items, typically identical or similar, for example container nests <NUM>, being relocated or transferred simultaneously or "in parallel". In this respect the process is distinguished from a process in which the same items are being "serially relocated" or "serially transferred". In the latter case the items are relocated or transferred one at a time. The present invention comprises subsystems having means arranged for batch transfer of container nests, while other means are arranged for serial transfer. A means arranged for batch transfer can serially transfer individual container nests. However, means arranged for serial transfer of container nests cannot batch transfer pluralities of container nests.

<FIG> shows articulated robotic arm subsystem <NUM> in more detail. Following the terminology suggested by the parallels with the human anatomy of shoulders, upper arms, forearms and joined or tied wrists, the articulating elements of the robotic arm subsystem <NUM> are left and right upper arms 113a and 113b, and left and right forearms 113c and 113d. Rotary elbows 112c and 112d join the left forearm 113c to the left upper arm 113a, and the right forearm 113d to the right upper arm 113b respectively. Actuator assembly <NUM>, disposed at a proximal end of robotic arm subsystem <NUM>, provides both the rotary action and the vertical motion of left rotary shoulder 112a and right rotary shoulder 112b. Forearms 113c and 113d are joined at rotary wrist <NUM> that allows forearms 113c and 113d to articulate with respect to each other. Rotary elbows 112c and 112d may be unpowered, all required power for the articulation being provided by actuator assembly <NUM>. The articulation of robotic arm subsystem <NUM> is therefore driven only at the proximal or shoulder end of robotic arm subsystem <NUM>.

The actuator assembly <NUM> can be implemented with left and right rotary actuators that respectively drive the output shafts that drive the shoulders, or with a single actuator and a suitable rotary mechanism to drive the output shafts in opposite directions (e.g., a gearbox). The actuator assembly <NUM> is preferably enclosed in a housing to isolate the actuators from the inside of the loading subsystem <NUM>. The actuator assembly may also include one or more linear actuators to lift the output shafts, allowing the nests to be lifted and set down by the robotic arm subsystem <NUM>.

Rotary shoulders 112a and 112b rotate about shoulder rotational axes 119a and 119b respectively. Rotary elbows 112c and 112d rotate about elbow rotational axes 119c and 119d respectively. Rotary wrist <NUM>, located at the distal end of robotic arm subsystem <NUM>, rotates about wrist rotational axis 119e. Rotary wrist <NUM> further allows fork-and-pusher baseplate <NUM> to rotate about rotary axis 119e. To this end rotary wrist <NUM> is equipped with a suitable drive (not shown) to rotate baseplate <NUM>. Suitable drives may be, for example without limitation, a worm drive.

Robotic arm subsystem <NUM> is capable of rotating the forearms 113c and 133d "inward" to extend further in the proximal direction than the shoulders 112a and 112b. This allows robotic arm subsystem <NUM> to move fork-and-pusher baseplate <NUM> to container nest pedestal <NUM> of <FIG> and <FIG>, allowing fork-and-pusher baseplate <NUM> to pass between rotary elbows 112c and 112d and over rotary shoulders 112a and 112b in that process. The vertical extent of the rotary elbows 112c and 112d makes this articulation possible.

When left and right rotary shoulders 112a and 112b are rotated respectively anticlockwise and clockwise (looking down on actuator assembly <NUM>), rotary elbows 112c and 112d separate further from each other and rotary wrist <NUM> bearing baseplate <NUM> is moved closer to the actuator assembly <NUM>. With reference to <FIG> it may be seen that such an articulated action moves the baseplate <NUM> closer to the pedestals <NUM>. In order to collect nests <NUM> bearing containers <NUM> from the pedestals <NUM>, baseplate <NUM> may be fitted with a fork <NUM> disposed for engaging with the nests bearing the containers, as shown in <FIG>. To the extent that different nests <NUM> of differing sizes and shapes may be employed, baseplate <NUM> may be fitted with different forks <NUM> to match the different nests <NUM>. Baseplate <NUM> may also be fitted with at least one pusher <NUM>, four pushers being shown in <FIG>. The purpose and function of pushers <NUM> will become clear at the hand of <FIG>.

Different detailed embodiments are possible for the upper arms and forearms of robotic articulated arm subsystem <NUM>. In <FIG> rotary elbow 112c is shown as greater in vertical extent than rotary elbow 112d, such that forearms 113c and 113d are not articulating in the same horizontal plane, as is evident from the arrangement of rotary wrist <NUM>. In other embodiments, the rotary elbows may be identical and the forearms 113c and 113d articulate differently at rotary wrist <NUM>. In one embodiment, with the baseplate <NUM> and fork <NUM> in the orientation shown in <FIG>, the empty fork <NUM> can pass under the forearms 113c and 113d and over the rotary shoulders 112a and 112b in order to reach the pedestals <NUM> shown in <FIG> and <FIG>.

In <FIG>, fork <NUM> is shown depositing through portal <NUM> nest <NUM> bearing containers <NUM> on shelf <NUM> of lyophilizer subsystem <NUM>. To facilitate this action, lyophilizer door <NUM> is in the open position. Door <NUM> is capable of being sealed. As may be seen in <FIG>, the vertical level of pedestal <NUM> is comparable to that of the shelf <NUM> of the lyophilizer <NUM> being supplied with nests <NUM>. This arrangement facilitates baseplate <NUM> and its attached pushers <NUM> and fork <NUM> in passing between the rotary elbows 112d and 112c (partly obscured behind 112d in <FIG>) in order to collect further nests of containers from the pedestal <NUM>. <FIG> shows further shelves within lyophilizer subsystem <NUM>. Robotic arm subsystem <NUM> is therefore employed in a first orientation in placing nests <NUM> at a first location in lyophilizer subsystem <NUM> and then subsequently employed in a second orientation to move nests <NUM> to a second location in lyophilizer subsystem <NUM>. In order to vertically stack shelves <NUM>, shelves <NUM> may be mounted on an elevator system that moves them upward once loaded with container nests.

Once a container bearing nest <NUM>, or row of container bearing nests <NUM>, has been placed on shelf <NUM>, and fork <NUM> withdrawn from the nest(s) <NUM>, baseplate <NUM> may be rotated through <NUM> degrees so that pusher(s) <NUM> face(s) the nest(s) <NUM>. Actuator assembly <NUM> may then be operated to push nest(s) <NUM> further onto the shelf to predetermined or desired positions by means of pushers(s) <NUM>, thereby creating room for another nest <NUM> or row of nests <NUM> on shelf <NUM>. When a shelf <NUM> has been filled to a desired degree with nests <NUM>, the shelf <NUM> may be raised using the elevator system of the lyophilizer <NUM>.

Returning now to <FIG>, pharmaceutical container filling subsystem <NUM> may be, for example, of the type described in detail in <CIT> and No. <CIT>, both titled "Robotic filling systems and methods", the specifications of which are incorporated herewith in full. This general kind of system is also described in <CIT>, titled "Articulated arm apparatus and system", the specification of which is also incorporated herewith in full. Pharmaceutical containers <NUM> may be filled with a pharmaceutical substance in filling subsystem <NUM> while borne in nests <NUM>. Nests <NUM> suitable for use with the present invention include, but are not limited to, those described in WIPO patent application <CIT>), titled "Method, device and system for filling pharmaceutical containers" and in WIPO patent application <CIT>) titled "Cover removal system for use in controlled environment enclosures,".

Accumulator subsystem <NUM> may comprise a robotic arm (not shown) for obtaining nests <NUM> with filled containers <NUM> from filling subsystem <NUM> and for storage of such nests <NUM> of containers <NUM> in accumulator subsystem <NUM>. The arm, or another similar articulated robotic arm may be employed to place a nest <NUM> bearing containers <NUM> at the source location in tunnel <NUM>.

The embodiment shown in <FIG> allows for containers nests <NUM> to be batch transferred to lyophilizer subsystem <NUM> while other container nests <NUM> are at the same time being serially transferred from the accumulator subsystem <NUM> to lyophilizer loader subsystem <NUM>, and yet further container nests <NUM> are at the same time having their containers <NUM> filled in filling subsystem <NUM>.

In a further aspect, described at the hand of the flow chart of <FIG>, a method is presented for lyophilizing a pharmaceutical substance in an integrated pharmaceutical processing system, the method comprising: providing [<NUM>] in the integrated pharmaceutical processing system <NUM> a plurality of pharmaceutical containers <NUM> held in a plurality of container nests <NUM>; sealing [<NUM>] an interior chamber of the integrated pharmaceutical processing system <NUM> against an external environment; establishing [<NUM>] in the interior chamber of the pharmaceutical processing system <NUM> an aseptic condition; at a filling station within the interior chamber of the processing system <NUM> depositing [<NUM>] the pharmaceutical substance into at least a portion of the plurality of containers <NUM> in the at least one container nest <NUM>; batch relocating [<NUM>] the plurality of container nests <NUM> with pharmaceutical containers <NUM> to an interior chamber of a lyophilizer <NUM> without unsealing the integrated pharmaceutical processing system <NUM>; sealing [<NUM>] an interior chamber of the lyophilizer <NUM> from a remainder of the integrated pharmaceutical processing system <NUM>; and lyophilizing [<NUM>] the pharmaceutical substance contained in the at least a portion of the plurality of containers <NUM> in the at least one container nest <NUM>.

The method may further comprise serially transferring [<NUM>] within the processing system <NUM> from the filling station to an interior chamber of an accumulator subsystem <NUM> a plurality of container nests <NUM> bearing containers <NUM> containing the pharmaceutical substance; and serially transferring [<NUM>] within the interior chamber of the processing system <NUM> the at least one container nest <NUM> from the interior chamber of the accumulator subsystem <NUM> to a nest access location <NUM> in an interior chamber of a lyophilizer loading subsystem <NUM>, wherein the at least one container nest <NUM> is at least one of the plurality of container nests.

The batch relocating may comprise operating a first articulated robotic arm <NUM> to engage with the plurality of container nests <NUM>; and operating the first articulated robotic arm <NUM> to place the plurality of container nests <NUM> at a first location in the interior chamber of the lyophilizer <NUM>. The batch relocating [<NUM>] may further comprise operating the first articulated robotic arm <NUM> to move the plurality of nests <NUM> from the first location in the interior chamber of the lyophilizer <NUM> to a second location in the interior chamber of the lyophilizer <NUM>.

The batch relocating [<NUM>] may comprise operating an articulated robotic arm <NUM> to engage with the container nests <NUM> at the nest access location <NUM>; and operating the first articulated robotic arm <NUM> to place the container nests <NUM> at a first location in the interior chamber of the lyophilizer <NUM>. The method may further comprise operating the first articulated robotic arm <NUM> to move the container nests <NUM> from the first location in the interior chamber of the lyophilizer <NUM> to a second location in the interior chamber of the lyophilizer <NUM>.

In a further aspect, described at the hand of the flow chart in <FIG>, a method for lyophilizing a pharmaceutical substance comprises at least partially filling [<NUM>] under an aseptic condition within a sealed processing chamber, for example the interior chamber of system <NUM>, a first plurality of containers <NUM> with the pharmaceutical substance while the first plurality of containers <NUM> is held in a container nest <NUM>; batch transferring [<NUM>] to a lyophilizer <NUM> a plurality of container nests <NUM> bearing containers <NUM> containing the pharmaceutical substance; and operating [<NUM>] the lyophilizer <NUM> to lyophilize the pharmaceutical substance, wherein the plurality of container nests <NUM> comprises the at least one container nest containing the at least partially filled first plurality of containers <NUM>. The batch transferring to a lyophilizer <NUM> a plurality of container nests <NUM> may be undertaken under the aseptic condition.

The method may further comprise at least partially filling [<NUM>] a second plurality of containers with the pharmaceutical substance while batch transferring [<NUM>] to the lyophilizer the plurality of container nests. The method may further comprise sealing [<NUM>] an interior chamber of the lyophilizer <NUM> from the interior of the processing chamber of the system <NUM> while maintaining the aseptic condition in the processing chamber of the system <NUM>. The batch transferring [<NUM>] may comprise operating an articulated robotic arm <NUM> to engage with the plurality of container nests <NUM>; and operating the articulated robotic arm <NUM> to transfer the container nests <NUM> to a first location in the lyophilizer <NUM>. The method may further comprise operating the articulated robotic arm <NUM> to move the container nests <NUM> from the first location in the lyophilizer <NUM> to a second location in the lyophilizer <NUM>.

The arm actuators, doors, and other controllable parts of the system are preferably controlled by a control system. This control system can be implemented in connection with special-purpose software programs running on general-purpose computer platforms or application-specific controller platforms, but it could also be implemented in a variety of other ways including through the use of special-purpose hardware for some or all of the control system. And while the system can be broken into the series of modules and steps shown for illustration purposes, one of ordinary skill in the art would recognize that it is also possible to combine them and/or split them differently to achieve a different breakdown, and that the functions of such modules and steps can be arbitrarily distributed and intermingled within different entities, such as routines, files, and/or machines. Moreover, different providers can develop and even operate different parts of the system.

Claim 1:
An integrated pharmaceutical processing system (<NUM>), comprising:
an actuator assembly (<NUM>) including:
a housing having first and second shaft openings;
at least one rotary actuator held in the housing;
a first output shaft that passes through the first shaft opening in the housing, has a first end responsive to the at least one rotary actuator inside the housing, and has a second end outside the housing;
a second output shaft located proximate that first output shaft, wherein the second output shaft passes through the second shaft opening in the housing, has a first end responsive to the at least one rotary actuator inside the housing, and has a second end outside the housing;
a first upper arm (113a) having a first end connected to the second end of the first shaft and a having a second end so that it is at least generally perpendicular to an axis of rotation of the first shaft;
a second upper arm (113b) having a first end connected to the second end of the second shaft and having a second end so that it is at least generally perpendicular to an axis of rotation of the second shaft;
a first forearm (113c) having a first end and a second end;
a second forearm (113d) having a first end and a second end;
a first articulation between the second end of the first upper arm and the first end of the first forearm;
a second articulation between the second end of the second upper arm and the first end of the second forearm;
a wrist member (<NUM>) including:
an articulation mount having an axis of rotation (119e);
at least one nest support structure to support a multi-container nest on one side of the axis of rotation of the articulation mount;
a pushing surface (<NUM>), located opposite the axis of rotation of the articulation mount from the nest support structure, that is at least generally parallel to the axis of rotation of the articulation mount;
a third articulation between the second end of the first forearm and the second end of the second forearm, wherein the axes of rotation of the first and second output shafts, and the axes of the first, second, and third articulations are at least generally parallel to define a five-bar linkage, and
a rotary wrist actuator between the third articulation and the wrist member articulation mount.