U.S. patent application number 16/559388 was filed with the patent office on 2020-02-27 for devices and methods for formulation processing.
The applicant listed for this patent is Dr. Py Institute LLC. Invention is credited to Julian V. Chan, Daniel Py, Debashis Sahoo.
Application Number | 20200062430 16/559388 |
Document ID | / |
Family ID | 59314366 |
Filed Date | 2020-02-27 |
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United States Patent
Application |
20200062430 |
Kind Code |
A1 |
Py; Daniel ; et al. |
February 27, 2020 |
DEVICES AND METHODS FOR FORMULATION PROCESSING
Abstract
Apparatuses and methods for controlling transfer of substances
to a formulation container to provide a predetermined formulation.
A controller may utilize one or more of a flow time, flow rate or a
volume of transfer of substance. Barcoded and RFID-containing
components may be used to determine what connection or
disconnection has been made, and/or time thereof. Process
compliance may compare measured or determined flow or connection
time, flow rate and/or the transfer volume to a predetermined time,
flow rate and/or volume, and adjust one or more of the time, flow
rate and/or the volume of the transfer. An optional holder or
cradle is configured to receive therein a fluid transfer connector
formed by the connection of first and second connector portions,
each in fluid communication with a flow conduit or channel that
delivers substance to or receives substance from its respective
connector portion, only if the connector portions are properly
connected together. One or more sensors may be used to determine
identification information of the connector and/or flow rates of
substance through the connector.
Inventors: |
Py; Daniel; (Larchmont,
NY) ; Sahoo; Debashis; (Danbury, CT) ; Chan;
Julian V.; (New Milford, CT) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Dr. Py Institute LLC |
New Milford |
CT |
US |
|
|
Family ID: |
59314366 |
Appl. No.: |
16/559388 |
Filed: |
September 3, 2019 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15410758 |
Jan 19, 2017 |
10399713 |
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16559388 |
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62280696 |
Jan 19, 2016 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61M 39/10 20130101;
A61M 2039/1044 20130101; B65B 3/30 20130101; B65B 3/36 20130101;
A61M 39/165 20130101; B65B 57/18 20130101; A61J 2205/60 20130101;
A61J 2205/10 20130101; A61J 1/2048 20150501; B65B 55/08 20130101;
B65B 3/28 20130101; A61J 3/002 20130101; B65B 3/12 20130101; B65B
3/003 20130101 |
International
Class: |
B65B 3/00 20060101
B65B003/00; A61J 1/20 20060101 A61J001/20; B65B 3/12 20060101
B65B003/12; B65B 3/28 20060101 B65B003/28; B65B 3/30 20060101
B65B003/30; B65B 3/36 20060101 B65B003/36; A61M 39/16 20060101
A61M039/16; A61M 39/10 20060101 A61M039/10 |
Claims
1. An apparatus for controlling transfer of a substance to maintain
a predetermined formulation, the apparatus comprising: a cradle
having a body defining a first interior cavity portion therein
configured to receive therein a substance transfer connector formed
by the connection of a first connector portion and a second
connector portion, wherein the cradle is configured and dimensioned
to receive the connector therein only when the first connector and
the second connector are properly connected together.
2. An apparatus as defined in claim 1, wherein the first interior
cavity portion includes at least a portion of a reader or sensor
configured to read or determine identification information of the
connector, and the apparatus is further configured to transmit said
identification information to a controller configured to control
substance transfer flow though the connector.
3. An apparatus as defined in claim 2, wherein the identification
information is contained on or in an RFID tag included on the
connector, and the reader or sensor includes an RFID reader.
4. An apparatus as defined in claim 2, wherein the identification
information is contained in a barcode contained on the connector,
and the reader or sensor includes a bar code reader.
5. An apparatus as defined in claim 1, further including a detector
configured to detect whether the connector is properly located
within the first interior cavity portion, and to transmit to a
controller, which is configured to control substance transfer flow
though the connector, information representing that the connector
is properly located within the first interior cavity portion.
6. An apparatus as defined in claim 5, wherein the detector is
mechanical, electromechanical, or electronic.
7. An apparatus as defined in claim 5, wherein the detector
includes a switch having and movable between a first position when
the connector is not properly located in the first interior cavity
portion and a second position when the connector is properly
located in the first interior cavity portion, and configured to, in
the second position, transmit information to the controller
representing that the connector is properly located within the
first interior cavity portion.
8. An apparatus as defined in claim 7, wherein the switch is biased
in a direction from the second position toward the first
position.
9. An apparatus as defined in claim 1, wherein the cradle further
defines a second interior cavity portion configured to receive
therein a portion of a flow conduit in or placeable in fluid
communication with the connector, and includes a flow meter
configured to measure flow of substance through the flow conduit,
wherein the apparatus is further configured to transmit a flow
measurement to a controller configured to control substance
transfer flow though the connector.
10. An apparatus as defined in claim 1, further comprising a cover
movable relative to the body between an open position and a closed
position, wherein in the closed position the cover sufficiently
blocks access to the first interior cavity portion to prevent (1)
insertion of said connector into the first interior cavity portion
when the connector is not located in the cradle and (2) removal of
said connector from the first interior cavity portion when the
connector is located therein, and an open position where the cover
does not block access to the first interior cavity portion to allow
(1) insertion of said connector into the first interior cavity
portion when the connector is not located therein and (2) removal
of said connector from the first interior cavity when the connector
is located within the cradle.
11. The apparatus of claim 10, further including a detector
configured to detect whether the cover is in an open position or a
closed position, and to transmit to a controller, which is
configured to control substance transfer flow though the connector,
information representing that the cover is in the closed
position.
12. An apparatus as defined in claim 11, wherein the detector is
mechanical, electromechanical, or electronic.
13. An apparatus as defined in claim 11, wherein the detector
includes a switch having and movable between a first position when
the cover is in the open position and a second position when the
cover is in the closed position, and configured to, in the second
position, transmit information to the controller representing that
the cover is in the closed position.
14. An apparatus as defined in claim 13, wherein the switch is
biased in a direction from the second position toward the first
position.
15. The apparatus of claim 10, wherein one or more of the body or
the cover defines at least one opening therein configured to permit
viewing of the connector in the cradle when the cover is in the
closed position.
16. A method for controlling transfer of a substance to maintain a
predetermined formulation comprising: placing a substance transfer
connector having a first connector portion and a second connector
portion into a properly connected position by connecting the first
and second connector portions; and inserting the properly connected
connector into a cradle having a body defining a first interior
cavity portion therein configured to receive therein said connector
only when the first connector portion and the second connector
portion are properly connected together, such that the connector is
received in the first interior cavity portion.
17. A method as defined in claim 16, further including sensing
identification information of the connector, and transmitting said
identification information to a controller configured to control
substance transfer flow though the connector.
18. A method as defined in claim 17, wherein the identification
information is contained on or in an RFID tag, and the sensing step
includes sensing said identification information with an RFID
reader.
19. A method as defined in claim 17, wherein the identification
information is contained in a barcode contained on the connector,
and the sensing step includes sensing said identification
information with a barcode reader.
20. A method as defined in claim 16, further including detecting
whether the connector is properly located within the first interior
cavity portion, and transmitting to a controller, which is
configured to control substance transfer flow though the connector,
information representing that the connector is properly located
within the first interior cavity portion.
21. A method as defined in claim 20, further including transferring
substance through said connector only when said connector is
properly located within the first cavity portion.
22. A method as defined in claim 20, wherein the detecting step
includes moving a switch from a first position where the connector
is not properly located in the first interior cavity portion to a
second position where the connector is properly located in the
first interior cavity portion, and then transmitting said
information to the controller representing that the connector is
properly located within the first interior cavity portion.
23. A method as defined in claim 22, further including biasing the
switch in a direction from the second position toward the first
position.
24. A method as defined in claim 16, wherein the cradle further
defines a second interior cavity portion configured to receive
therein a portion of a flow conduit in or placeable in fluid
communication with the connector, and includes a flow meter
configured to measure flow of substance through the flow conduit,
and the method further includes inserting said flow conduit portion
into the second interior cavity portion and transmitting a
measurement of substance flow through said flow conduit portion to
a controller configured to control substance transfer flow though
the connector.
25. A method as defined in claim 16, wherein the cradle includes a
cover movable relative to the body between an open position and a
closed position, and the method further includes moving the cover
from the open to the closed position and transmitting to a
controller, which is configured to control substance transfer flow
though the connector, information representing that the cover is in
the closed position.
26. A method as defined in claim 25, further including detecting
whether the cover is in the open position or the closing position
prior to the transmitting step.
27. A method as defined in claim 26, wherein the detecting step
includes moving a switch from a first position where the cover is
in the open position to a second position where the cover is in a
closed position.
28. A method as defined in claim 27, further including biasing the
switch in a direction from the second position toward the first
position.
29. A method as defined in claim 16, further including engaging a
flow conduit in or placeable in fluid communication with the
connector with a pump configured to pump substance in the flow
conduit through the connector in the properly connected position.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This patent application is a divisional claiming the benefit
under 35 U.S.C. .sctn. 120 of similarly-titled U.S. patent
application Ser. No. 15/410,758 filed on Jan. 19, 2017, which
claims priority under 35 U.S.C. .sctn. 119 to U.S. Provisional
Patent Application No. 62/280,696, entitled "Formulation
Processing," filed Jan. 19, 2016, which are hereby incorporated by
reference as part of the present disclosure.
FIELD OF THE INVENTION
[0002] The present invention relates to apparatuses and methods for
controlling and documenting transfer of substances for the
manufacture of a formulation, and more particularly, to devices for
use in controlling and documenting same, and to related methods of
making and using same.
BACKGROUND INFORMATION
[0003] Generally, process control for the manufacturing or
formulation of a product is important if not critical to providing
a product of desired quality and/or that meets specifications.
Deviation from the specified process can negatively affect quality,
and in some situations can be dangerous. For some industries or
products, deviation from specification may violate laws or
regulations.
[0004] One industry in which specified product quality is often
necessary is pharmaceutical manufacturing. Three main objectives
typically govern the pharmaceutical manufacturing process. The
first objective may be to maintain sterility of critical surfaces
within the receiving chambers that contain the ingredient
substances used in the manufacture and the manufactured
formulations themselves. The second objective may be to maintain
consistency and quality of the formulation being manufactured. Most
formulations are a combination of different ingredients. These
ingredients need to be blended in the most sustainable manner in
order to ensure consistent quality of the resultant formulation for
use by a patient. The third objective may be to avoid or limit
particulate issues contaminating the ingredients as well as the
formulation being manufactured. Traditional aseptic manufacturing
involve a process by which sterile substances are transferred into
sterile receiving chambers and the receiving chambers are closed
after completion of filling--all within a classified
environment.
SUMMARY OF THE INVENTION
[0005] Accordingly, it is an object of the present invention to
overcome one or more of the above described drawbacks and/or
disadvantages of the prior art.
[0006] In one aspect, apparatuses can be used to control transfer
of a substance to maintain a predetermined formulation. The
apparatus includes a cradle or holder having a body defining a
first interior cavity portion therein configured to receive therein
a fluid transfer connector formed by the connection of a first
connector portion and a second connector portion. The cradle is
configured and dimensioned to receive the connector therein only
when the first connector and the second connector are properly
connected together. In some embodiments, the first interior cavity
portion includes a sensor configured to determine identification
information of the connector, the apparatus may transmit such
identification information to a controller configured to control
fluid transfer flow though the connector. In some such embodiments,
the connector includes an RFID tag, and the cradle includes an RFID
reader. In other such embodiments, the connector contains a
barcode, and the cradle includes a bar code reader.
[0007] In further embodiments, the cradle includes a detector
configured to detect whether the connector is properly located
within the first interior cavity portion, and transmits to the
controller that the connector is and/or is not properly located
within the first interior cavity portion. The detector may be
mechanical, electromechanical, or electronic. In one embodiment,
the detector includes a switch movable between a first position
when the connector is not properly located in the first interior
cavity portion and a second position when the connector is properly
located in the first interior cavity portion. In the second
position, information representing that the connector is properly
located within the first interior cavity portion is transmitted to
the controller. In a further embodiment, the switch is biased in a
direction from the second position to the first position so as to
provide a default a condition that the connector is not properly in
the cavity.
[0008] In other embodiments, the cradle has a second interior
cavity portion that receives a portion of a flow conduit in fluid
communication with the connector. A flow meter measures flow of
fluid through the flow conduit and transmits the measured flow to
the controller.
[0009] The cradle may include a cover movable between open and
closed positions. When opened, the connector and/or the flow
conduit portion may be inserted into the cradle. When closed,
access to the interior cavities of the cradle is blocked. In some
such embodiments, the cradle includes a cover position detector
configured that detects whether the cover is open or closed. When
closed, the detector transmits information representing such to the
controller. The detector can be mechanical, electromechanical, or
electronic. In one embodiment, the detector includes a switch
movable between a first position when the cover is open and a
second position when the cover is closed. In the second position,
information that the cover is closed is transmitted to the
controller. In a further embodiment, the switch is biased in a
direction from the second position to the first position so as to
provide a default a condition that the cover is open.
[0010] In another aspect, methods are provided for controlling
transfer of a substance to maintain a predetermined formulation. A
first connector portion and a second connector portion of a fluid
transfer connector are connected. The connector is into a cradle
having a body with a first interior cavity portion configured and
dimensioned to allow the connector therein only if when the first
connector and the second connector are properly connected together,
such that the connector is received in the first interior cavity
portion. In some embodiments, the method includes sensing
identification information of the connector, and transmitting said
identification information to a controller configured to control
fluid transfer flow though the connector. In some such embodiments,
the connector includes an RFID tag, and an RFID reader senses the
identification information. In other embodiments, the connector
contains a barcode, and a bar code reader reads the identification
information in the barcode.
[0011] In further embodiments, the method further includes
detecting whether the connector is properly located within the
first interior cavity portion, and if so, transmitting to the
controller information representing such. In some such embodiments,
the detecting includes moving a switch from a first position where
the connector is not properly located in the first interior cavity
portion to a second position where the connector is properly
located in the first interior cavity portion, and performing the
transmitting when the switch is in the second position. In further
embodiments, the switch is biased in a direction from the second
position to the first position to create a default condition that
the connector is not properly located in the cavity.
[0012] In embodiments where the cradle includes a second interior
cavity portion, a flow conduit in fluid communication with the
connector is inserted into the second interior cavity portion and a
flow meter measures flow in the conduit and transmits measurement
information the controller.
[0013] In embodiments where the cradle includes a cover, the method
may include detecting whether the cover is in an open position or a
closed position, and if closed, transmitting such information to
the controller. In some embodiments, such detection includes moving
a switch from a first position where the cover is in the open
position to a second position where the cover is in a closed
position. In some such embodiments, the switch is biased in a
direction from the second position to the first position to provide
a default condition that cover is detected as being open.
[0014] A method as defined in claim 16, further including engaging
a flow conduit in fluid communication with the connector with a
pump configured to pump fluid in the flow conduit through the
connector in the connected position.
[0015] One advantage of embodiments of the invention is that they
determine and thus ensure that the connector is properly connected
before substance is passed through the connector. Another advantage
of embodiments of the invention is that they prevent uncontrolled
human intervention and error in the production of a formulation.
Another advantage of embodiments of the invention is that they
enable high replication of product quality and composition among
formulation lots, and also among different producers utilizing
congruent formulation systems and process parameters.
[0016] Yet another advantage of embodiments of the invention is
that they enable management of inventory and ingredients. A further
advantage of embodiments of the invention is that they enable
adjustment of the formulation process based on inventory to prevent
deviation in formulation composition.
[0017] An additional advantage of embodiments of the invention is
that they permit remote monitoring, inspection and auditing of the
formulation process. Such remote activities may be performed using
recorded information or live, real-time information.
[0018] Yet an additional advantage of embodiments of the invention
is that they enable detection, mitigation and prevention of errors.
For example, when two or more components or ingredients are to be
mixed, mixing of incorrect ingredients can be avoided. The
controller may be programed to prevent the flow of ingredients,
e.g., to a mixing device, unless the controller confirms, through
information received by it that the correct connectors are
installed into respective cradles. If the bar code or RFID read
indicates that the connector installed in a cradle in the fluid
path to the mixing apparatus is associated with a component that is
not the component intended to be mixed, the controller may prevent
the operation of the system. For example, the controller may stop
operation of, or prevent or abstain from starting, a pump that
would pump components to the mixing device. Likewise, the
controller may close, or prevent or abstain from opening, valves
controlling fluid flow from the component source to the mixing
device. Further, in embodiment where the mixing apparatus is
mechanical in nature, the controller may stop operation, of or
prevent or abstain from operating, the mixing apparatus. These are
merely exemplary, however. The controller may take any action, or
not take any action, or combination of the same to prevent the flow
and/or mixing of substances from taking place. In addition, the
controller may activate an alarm or message informing a user of the
error and the action(s) taken or not taken by the controller.
[0019] Other embodiments can ensure components are mixed in the
correct sequence and/or prevent components from being mixed in the
incorrect sequence. Some formulations are required to be combined a
particular order. The controller may ensure that the components are
mixed in the correct order by allowing flow of components to the
mixing apparatus only in the correct order. The controller may also
prevent flow of components to the mixing apparatus if doing so
would cause the components to mix in the incorrect order. As an
example, if a three-component formulation must be mixed in a
certain order, the controller may be programmed with the proper
sequence of ingredients, e.g., ingredients I and II need to be
mixed before adding ingredient III. The controller can ensure that
ingredient III is not connected to (placed in fluid communication
with) the mixing chamber before ingredient II is connected and
added to the mixing chamber (and in the correct amount per the
formulation procedure). If a connector that is connected to an
ingredient and assigned to that ingredient in system is not
connected at the right time or sequence, e.g., as sensed by the
cradle via the RFID for that connector, the system may be
programmed to not allow that ingredient to flow to the mixing
chamber, such as, but not limited to, controlling the operation of
pertinent valves and/or pumps. Continuing with this example, if
after ingredient I is added to mixing chamber the connector
associated with ingredient III is connected to chamber, the system
will read that such connector is currently connected (via RFID and
the cradle), and, if so programmed, determine that it is the wrong
connection, and issue an alarm and/or not allow the process to
proceed--e.g., prevent pumps from operating or automatically
shutting a valve in line by (a) preventing ingredient III from
flowing out of its storage source (upstream of sterile connector)
and/or (b) preventing ingredient III from flowing into mixing
chamber (downstream of sterile connector but upstream of mixing
chamber). Prevention step (a) prevents ingredient III from ever
reaching the line that goes into the mixing chamber, where residual
substance in the line can "contaminate" the formulation or be
carried into the mixing chamber when the correct ingredient flows
through the line.
[0020] Other embodiment may, alternatively or in addition, control
or ensure proper residence time within a mixing or reaction
chamber. For example, some formulations require that ingredients
remain in the mixing and/or reaction chamber for a certain minimum
period of time in order for a desired, specified or required amount
of mixing to occur, e.g., sufficient mixing and/or homogenization,
and/or for a sufficient reaction, e.g., chemical, mechanical,
electrochemical, etc., to occur. Continuing with and modifying the
above-discussed example, if ingredients I and II not only need to
be mixed together prior to the addition of ingredient III, but
also, reside in the mixing chamber for a certain period of time
before adding ingredient III, e.g., to ensure full (or desired)
mixing or diffusion of ingredients, the controller may be programed
with the desired, specified or necessary residence time (or range
thereof). Via its connection with the system equipment (which may
be wired, wireless, or a combination thereof), the controller can
prevent or delay delivery of ingredient III to the mixing chamber
(e.g., via control of valves, pumps, etc.) until the proper
residence time is achieved. Conversely, if an ingredient, e.g.,
ingredient III is connected to the mixing chamber, as sensed by the
cradle (bar code and/or RFID), and their has been an insufficient
residence time, the control may prevent the process from proceeding
and/or prevent ingredient III from flowing into the mixing chamber,
e.g. prevent or shut down pumps from operating, automatically
shutting a valve in the fluid path, etc. The system may also issue
and alarm and/or notification of the status of the process. In
other embodiments, a residence time may apply to a single
ingredient rather than multiple ingredients, e.g., residence time
for sufficient dissolution of an ingredient in a solvent, residence
time for sufficient dilution of an ingredient to a desired,
specified or required concentration, etc.
[0021] In other embodiments, the amount of ingredient or product
delivered to a container, e.g., a mixing or storage container, by
measuring the weight of the container. The container may be
connected to or reside on a scale. The weight of the product
delivered to the container may be determined, for example, by
monitoring of a change in weight of the container during delivery
of the product thereto. A current weight (or change thereof) read
or measured by the scale may be transmitted to the controller. The
controller may be programmed with the specified weight of the
product or ingredient. The controller may then for example, help
ensure the specified amount of product is added by 1) flowing
substance to the container until the specified weight is added
and/or 2) preventing or ceasing flow of substance in excess of
specification, e.g., via control valves, pumps, etc. The system may
also issue notifications or alarms to indicate process status,
e.g., an overweight or underweight condition.
[0022] In further embodiments, process information and/or data as
read or determined by the system may be recorded for current or
future retrieval, monitoring, diagnosis, quality control or
certification. Such activities may be conducted off-site via
transmission or retrieval of such information and/or data.
[0023] Other objects and advantages of the present invention will
become more readily apparent in view of the following detailed
description of the currently preferred embodiments and the
accompanying drawings. It should be understood by those of ordinary
skill in the art that one or more features and/or embodiments of
the invention, alone and/or in combination, may be utilized with
respect to any parameter of a formulation or manufacturing
process.
[0024] However, while various objects, features and/or advantages
have been described in this Summary and/or will become more readily
apparent in view of the following detailed description and
accompanying drawings, it should be understood that such objects,
features and/or advantages are not required in all aspects and
embodiments.
[0025] This Summary is not exhaustive of the scope of the present
aspects and embodiments. Thus, while certain aspects and
embodiments have been presented and/or outlined in this Summary, it
should be understood that the present aspects and embodiments are
not limited to the aspects and embodiments in this Summary. Indeed,
other aspects and embodiments, which may be similar to and/or
different from, the aspects and embodiments presented in this
Summary, will be apparent from the description, illustrations
and/or claims, which follow.
[0026] It should also be understood that any aspects and
embodiments that are described in this Summary and do not appear in
the claims that follow are preserved for later presentation in this
application or in one or more continuation patent applications.
[0027] It should also be understood that any aspects and
embodiments that are not described in this Summary and do not
appear in the claims that follow are also preserved for later
presentation or in one or more continuation patent
applications.
BRIEF DESCRIPTION OF THE DRAWINGS
[0028] FIG. 1 is a schematic view of an apparatus configured to
control transfer of a substance comprising, among other components,
a flow meter and a connecting device, both in communication with a
controller such as a process logic controller (PLC);
[0029] FIG. 2 is a perspective view of a formulation receiving
chamber that receives transferred substances from one ore more of
the apparatus of FIG. 1;
[0030] FIG. 3 is a front view of a pouch containing a substance to
be transferred utilizing the apparatus of FIG. 1;
[0031] FIG. 4 is a side view of a connecting conduit with a single
use connector on a first end and a first connector at a second end,
the single use connector capable of forming a fluid-tight and/or
hermetic connection with a port of the pouch of FIG. 3, and the
first connector capable of forming a fluid-tight connection with a
second connector of the apparatus of FIG. 1;
[0032] FIG. 5 is a top view of a cradle with the cover of the
cradle in an open position.
[0033] FIG. 6 is a top view of the cradle of FIG. 5 with a
connector located therein;
[0034] FIG. 7 is a top view of the cradle of FIG. 6 with the cover
of the cradle in a closed position;
[0035] FIG. 8 is a front view of the cradle of FIG. 7;
[0036] FIG. 9 is a top perspective view of another embodiment of a
cradle with the cover of the cradle in an open position.
[0037] FIG. 10 is a top perspective view of the cradle of FIG. 9
with a connector located therein;
[0038] FIG. 11 is a top perspective view of the cradle of FIG. 9
with the cover of the cradle in a substantially closed
position.
[0039] FIG. 12 is a front perspective view of a system including a
pump, a connector in a connected position, and the cradle of FIGS.
9-11 with the cover in an open position.
[0040] FIG. 13 is a front perspective view of the system of FIG. 12
with the connector inlet tubing engaged with the pump and the
connector located in the cradle with the cover in an open
position.
[0041] FIG. 14 is a front perspective view of the system of FIG. 13
with the cover in a closed position.
DETAILED DESCRIPTION OF EMBODIMENTS
[0042] FIG. 1 shows an embodiment of an apparatus indicated
generally by the reference numeral 10. The device 10 in combination
with a controller 11a may be used to control transfer of substances
to maintain a predetermined formulation of the resulting
manufactured formulation. The apparatus described below can provide
control of both small-scale and large-scale sterile filling, for
example: for pharmaceutical and biotechnology research and
development, university teaching, research, and development,
clinical trials, analytical laboratories; at pharmacies, hospitals,
doctor's offices, extended care facilities, and/or emergency and
rescue operation areas for on-demand dispensing and production for
customers and patients; at food processing plants; at facilities
for manufacturing and formulation trials, research, and production;
and can be used in emerging markets and countries.
[0043] As shown in FIG. 1, the apparatus, in one embodiment,
includes a flow meter 11, a barcoded first connector 13 in fluid
connection with a substance contained in a substance source, such
as but not limited to the pouch illustrated in FIG. 3, through a
first conduit, tube or channel 18, a barcoded second connector 15
forming a fluid-tight hermetic connection with the first connector
13, a second conduit, tube or channel 17 in fluid communication
with a formulation chamber, such as but not limited to the chamber
illustrated in FIG. 2, a barcode reader 19, a connecting device 16,
and communication channels 12, 14, and 19a that connect the flow
meter 11, the connecting device 16, and the barcode reader 19
respectively to the controller 11a.
[0044] The barcoded first connector 13 and the barcoded second
connector 15 may comprise connectors capable of forming a
fluid-tight and/or hermetic seal. In some embodiments, the first
connector 13 may comprise a sterile male connector and the second
connector 15 may comprise a sterile female connector, or vice
versa. Exemplary such sterile connectors are disclosed in the
following patents and co-pending patent applications, each of which
is hereby expressly incorporated by reference as part of the
present disclosure: U.S. patent application Ser. No. 13/450,306,
filed Apr. 18, 2012, entitled "Needle with Closure and Method,"
which claims the benefit of U.S. Provisional Application No.
61/476,523, filed Apr. 18, 2011, entitled "Filling Needle and
Method"; U.S. patent application Ser. No. 13/861,502, filed Apr.
12, 2013, entitled "Modular Filling Apparatus and Method," now U.S.
Pat. No. 8,966,866, which claims the benefit of similarly titled
U.S. Provisional Application No. 61/686,867, filed Apr. 13, 2012;
U.S. patent application Ser. No. 13/080,537, filed Apr. 5, 2011,
entitled "Aseptic Connector with Deflectable Ring of Concern and
Method", now U.S. Pat. No. 8,671,964, which claims the benefit of
similarly titled U.S. Provisional Application No. 61/320,857, filed
Apr. 5, 2010; U.S. patent application Ser. No. 13/864,919, filed
Apr. 17, 2013, entitled "Self-Closing Connector", which claims the
benefit of similarly titled U.S. Provisional Patent Application No.
61/635,258, filed Apr. 18, 2012, and similarly titled U.S.
Provisional Patent Application No. 61/625,663, filed Apr. 17, 2012;
U.S. patent application Ser. No. 13/874,839, filed May 1, 2013,
entitled "Device for Connecting or Filling and Method", which
claims the benefit of similarly titled U.S. Provisional Patent
Application No. 61/641,248, filed May 1, 2012, and similarly titled
U.S. Provisional Patent Application No. 61/794,255, filed Mar. 15,
2013; and U.S. patent application Ser. No. 14/536,566, filed Nov.
7, 2014, entitled "Device for Connecting or Filling and Method",
which claims the benefit of similarly to similarly-titled U.S.
Provisional Patent Application Nos. 61/641,248, filed May 1, 2012,
and 61/794,255, filed Mar. 15, 2013, each of which is hereby
expressly incorporated by reference in its entirety as part of the
present disclosure as if fully set forth herein.
[0045] In one embodiment, one of the connectors is a female
connector that is penetrable by a corresponding male connector to
place the male and female connectors in sterile, fluid
communication with each other, and to dispense the substance
contained in pouch 30 (FIG. 3) into the formulation chamber 20
(FIG. 2) therefrom. In one embodiment, the first connector 13 is
moved from a condition where it is not connected to the second
connector 15 toward and into engagement with the second connector
15 by the connecting device 16 so that the first connector housing
of the second connector 15 is slidably received within the
connector housing of the first connector 13 to form a fluid-tight
hermetic seal and a fluid path between the first connector 13 and
the second connector 15.
[0046] As may be recognized by those of ordinary skill in the
pertinent art based on the teachings herein, the fitments of the
first and second connectors 13, 15 may take any of numerous
different configurations that are currently known, or that later
become known. For example, the fitment(s) may include only one
septum, may include more than two septa, may include one or more
septa and one or more sterile connectors, and/or may include one or
more sterile connectors without any septa, and a pouch or other
device may include more than one fitment. Further, the first and
second connectors may include a closed needle and septum
thereof.
[0047] The connecting device 16 may comprise any device now known
or later developed that is capable of connecting and disconnecting
the first and second connectors 13, 15. The connecting device 16,
in one embodiment, is in communication with the controller 11a, and
may be capable of connecting and disconnecting the first and second
connectors based on signals received from the controller. The
connecting device may also be coupled to the flow meter 11 with the
flow meter being located either immediately upstream or immediately
downstream (as in FIG. 1) of the connecting device 16.
[0048] In one embodiment, the flow meter 11 may comprise a device
that measures, determines or meters the flow of a substance through
the first channel 18. In one embodiment, the flow meter 11 may be
capable of measuring the flow rate of the substance without making
physical contact with the substance within the first conduit 18,
e.g., located entirely externally thereto. The flow meter may use
optical, laser, ultrasonic, magnetic or other technologies now
known and later developed to measure the flow rate of the
substance. The flow meter 11 may then communicate this information
to the controller. In one embodiment, the controller comprises a
process logic controller (PLC). The PLC controller may communicate
with various components of the apparatus 10, and other components
in the overall manufacturing environment either wirelessly or
through wired connections, as should be understood by those of
ordinary skill in the art.
[0049] The barcode reader 19 may comprise any suitable barcode
reading device now known or later developed that is capable of
reading barcodes present on an external surface of components such
as, for example, the first connector 13, the second connector 15,
the pouch 30 (FIG. 3), the formulation receiving chamber 20 (FIG.
2), and/or a connecting conduit (FIG. 4). By scanning and recording
the barcodes of each component in the system, proper connections
may be automatically controlled by the controller. The barcodes may
be in the form of a label attached to the components; alternately,
the barcodes may be molded onto the components during their
manufacture. The connecting device 16 is coupled with the barcode
reader 19 so that that the controller may coordinate automatic
reading of the barcode on each component entering and leaving the
system.
[0050] Referring now to FIG. 3, pouch 30 contains a substance that
is an ingredient of the intended formulation. Exemplary such
pouches are disclosed in the following co-pending patent
application, which is hereby expressly incorporated by reference as
part of the present disclosure: U.S. patent application Ser. No.
14/990,778, filed Jan. 7, 2016, entitled "Pouch with Sealed Fitment
and Method", which claims the benefit of similarly titled U.S.
Provisional Application No. 62/100,725, filed Jan. 7 2015, each of
which is hereby expressly incorporated by reference in its entirety
as part of the present disclosure as if fully set forth herein.
[0051] In the exemplary embodiment shown in FIG. 3, the pouch 30
includes a dispensing port 33, and a filling port 35. An exemplary
connector for connecting to the dispensing port 33 includes
connector 41 shown in FIG. 4, and the connectors are disclosed in
the U.S. Provisional Application entitled "Single Use Connectors"
filed on even date herewith, which is hereby expressly incorporated
by reference as part of the present disclosure. In the exemplary
embodiment shown in FIG. 3, the pouch is filled with a substance
31. In one embodiment, the substance 31 may comprise sterile or
purified water for water fall injection (WFI). In alternate
embodiments, the substance 31 may be any component or ingredient of
a formulation or product. In the illustrated embodiment, pouch 30
may be filled through a penetrable and resealable septum 37
overlying the filling port 35, the septum 37 being in fluid
connection with an internal chamber of the pouch 30. The dispensing
port 33 may also include a penetrable septum in fluid connection
with an internal chamber of the pouch 30, which may be penetrated
by a connector, e.g., connector 41 to place a fluid conduit, e.g.,
conduit 18, in fluid communication with the substance 31 for
dispensing through the conduit 18. The septums of the ports 33, 35
maintain the interior of the pouch 30 hermetically sealed from the
ambient atmosphere. Alternatively, the dispensing port 33 and/or
filling port 35 may include a valve or other device that maintains
interior of the pouch 30 in sealed condition but allows a connector
to be placed into fluid communication therewith. In one embodiment,
the pouch 30 may include barcodes readable by a barcode reader,
such as the barcode reader 19 (FIG. 1).
[0052] Prior to filling the pouch with substance 31, the pouch 30
and the pouch's internal and/or external surfaces may be
sterilized. The apparatus and methods for sterilizing the pouch and
its external surfaces may take the form of any of the apparatus and
methods disclosed in the following commonly assigned patents and
patent applications which are hereby expressly incorporated by
reference as part of the present disclosure: U.S. patent
application Ser. No. 10/766,172, filed Jan. 28, 2004, entitled
"Medicament Vial Having A Heat-Sealable Cap, And Apparatus and
Method For Filling The Vial", which is a continuation-in-part of
similarly titled U.S. patent application Ser. No. 10/694,364, filed
Oct. 27, 2003, which is a continuation of similarly titled
co-pending U.S. patent application Ser. No. 10/393,966, filed Mar.
21, 2003, which is a divisional of similarly titled U.S. patent
application Ser. No. 09/781,846, filed Feb. 12, 2001, now U.S. Pat.
No. 6,604,561, issued Aug. 12, 2003, which, in turn, claims the
benefit of similarly titled U.S. Provisional Application Ser. No.
60/182,139, filed Feb. 11, 2000; and U.S. Provisional Patent
Application No. 60/443,526, filed Jan. 28, 2003; and similarly
titled U.S. Provisional Patent Application No. 60/484,204, filed
Jun. 30, 2003; U.S. patent application Ser. No. 10/655,455,
entitled "Sealed Containers And Methods Of Making And Filling
Same", filed Sep. 3, 2003, which, in turn, claims the benefit of
similarly-titled U.S. Provisional Patent Application No. 60/408,068
filed Sep. 3, 2002; U.S. Provisional Patent Application No.
60/551,565, filed Mar. 8, 2004, titled "Apparatus and Method for
Molding and Assembling Containers with Stoppers"; U.S. patent
application Ser. No. 10/600,525 filed Jun. 19, 2003 titled "Sterile
Filling Machine Having Needle Filling Station Within E-Beam
Chamber", which, in turn, claims the benefit of similarly-titled
U.S. Provisional Application No. 60/390,212 filed Jun. 19, 2002;
U.S. patent application Ser. No. 10/983,178 filed Nov. 5, 2004
titled "Needle Filling and Laser Sealing Station", which, in turn,
claims the benefit of similarly-titled U.S. Provisional Patent
Application No. 60/518,267 filed Nov. 7, 2003 and similarly-titled
U.S. Provisional Patent Application No. 60/518,685 filed Nov. 10,
2003; U.S. Provisional Patent Application No. 60/550,805 filed Mar.
5, 2004 titled "Apparatus for Needle Filling and Laser Resealing";
and U.S. patent application Ser. No. 08/424,932 filed Apr. 11, 1995
now U.S. Pat. No. 5,641,004 issued Jun. 24, 1997 titled "Process
for Filling a Sealed Receptacle Under Aseptic Conditions."
[0053] Referring now to FIG. 4, connecting conduit 40 represents a
conduit through which sterile transfer of the substance 31 (FIG. 3)
occurs. As shown in FIG. 4, one end of the connecting conduit
terminates in a connector 41 while the other end terminates in the
first connector 13, with the channel 18 fluidically connecting the
two connectors. In one embodiment, the first connector 13 may
comprise a sterile male connector that forms a fluid-tight hermetic
seal with the second connector 15 of FIG. 1, or with second
connectors 15a, 15b, and 15c shown in FIG. 2.
[0054] Referring now to FIG. 2, formulation-receiving chamber 20
may be a sterile and/or closed to the ambient atmosphere, and may
include second connectors 15a, 15b, and 15c, and third connector
25, with each of these connectors in fluid communication with the
formulation chamber. In one embodiment, the formulation chamber 20
may comprise a large blending tank or a blending pouch into which
ingredients may be introduced to produce a formulation therein. The
second connectors 15a, 15b, and 15c may be similar in structure and
function to the first connector 13 or the second connector 15
described with reference with FIG. 1. The formulation chamber 20
may receive substances via the connectors 15a, 15b 15c, and 25 with
substances received into and mixing or blending within the chamber.
For each connection, the flow rate of each of the substances is
measured by a device (in communication with the controller) such as
described above with reference to FIG. 1. The time the connection
is its connected state may also be recorded by the controller,
e.g., based on signals from the connecting device 16 that a
connection or disconnection has been made. Accordingly, based on
the measured flow rate and connection time, the controller can
determine the volume of the materials that has been transferred
through the connection, e.g., into the formulation chamber 20.
[0055] The substances transferred into the formulation chamber 20
may be of any material suitable for such transfer. In one
embodiment, formulation chamber 20 may be prefilled with a
substance that occupies a portion of the formulation-receiving
chamber. In one embodiment, this substance may represent a powder
ingredient that forms part of the final formulation.
[0056] The controller may control transfer of substances from one
or more pouches 30 or other substance sources, with substance flow
from each and into the formulation-receiving chamber 20 being
regulated by the device 10, as follows. The controller may initiate
a fluid-tight hermetic connection of the connector 41 of the
connecting conduit 40 with the dispensing port 33 of the pouch 30,
the pouch 30 containing a substance that is an ingredient of the
intended formulation to be formed within the formulation chamber
20. The controller may then signal the connecting device 16 of the
device 10 to connect, e.g., form a fluid-tight hermetic seal
between, the first connector 13 located at the other end of the
connecting conduit 40 and the second connector in fluid connection
with the receiving chamber. The PLC controller may further signal
the barcode reader to read and transmit the barcodes of the pouch,
the first connector, the second connector, and optionally the
pouch, e.g., in order to determine what substance is being
transferred through what connection. After a fluid tight hermetic
seal is formed between the first and second connectors, transfer of
the substance from the pouch takes place, through the connecting
conduit 40 and into the fluid receiving chamber 20. In one
embodiment, the PLC controller may signal a pump (not shown) to
pump the material from its source and into the formulation chamber
20. In one embodiment, this pump comprises a peristaltic pump. The
peristaltic pump prevents any contact between pump parts and the
substance being transferred. Using a peristaltic pump for pumping
thus eliminates the need to sterilize the pump prior to use, or to
clean or re-sterilize the pump after completion of a sterile
transfer or before a change in the substance being transferred into
the formulation-receiving chamber.
[0057] The controller may further signal the flow meter 11 to
measure and transmit one or more of a time, flow rate, or a volume
of the substance being transferred. Alternatively, the flow meter
11 may transmit such information without receiving such a signal
from the controller. The flow meter 11 may be configured to measure
the flow rate at or near a barcoded component. The controller may
then compare the measured time, flow rate, and/or volume with a
predetermined time, flow rate and/or volume. Based on the
comparison, the controller may adjust one or more of the time, flow
rate (e.g., by controlling a pump or valve) or the volume of the
transfer of a given substance to provide a predetermined
formulation in the formulation receiving chamber. For example, the
controller may signal the connecting device 16 to disconnect the
connectors 13, 15 after a certain time of connection or volume of
transfer in order to cease the flow of substance to the formulation
chamber 20.
[0058] The controller may also record and store residence time and
distribution of each step of the processing and may automatically
control the consistency of the time the flow connection is made
(time of connection) and of the flow rates resulting in consistent
transfer/blending processing, thereby enabling continuous
manufacturing of fluid formulations. Using this method, the quality
and consistency of the manufactured formulation formed of different
mixed components can be measured and controlled by controlling the
time the flow connection is made for each substance being
transferred into the formulation chamber 20. In other words, the
precise amount and proportion of the various constituent substances
can be precisely controlled, and documented, to ensure high
quality, e.g., compliance, and/or consistency of the resulting
formulation. This method may thus result in a reproducible and
sustainable formulation process by which sterility and
particle-free nature of resulting formulation may be achieved. In
some embodiments, due to the closed construction of the system and
use of sterile connectors to make connections in the system, this
may be accomplished in Controlled Non-Classified (CNC) or even a
non-classified environment.
[0059] Upon completion of transfer of substance from each pouch or
substance source, the second connector 15 is disconnected from
formulation receiving chamber. The connecting conduit 40 along with
the pouch 30 to which the connector end 41 of the connecting
conduit 40 is attached may be discarded. Single use of these
components may help to avoid cross-contamination.
[0060] The apparatus and methods for sterilizing the pouch and its
external surfaces may take the form of any of the apparatus and
methods disclosed in the following commonly assigned patents and
patent applications which are hereby expressly incorporated by
reference as part of the present disclosure: U.S. patent
application Ser. No. 10/766,172, filed Jan. 28, 2004, entitled
"Medicament Vial Having A Heat-Sealable Cap, And Apparatus and
Method For Filling The Vial", which is a continuation-in-part of
similarly titled U.S. patent application Ser. No. 10/694,364, filed
Oct. 27, 2003, which is a continuation of similarly titled
co-pending U.S. patent application Ser. No. 10/393,966, filed Mar.
21, 2003,
[0061] In alternative embodiments, rather than using barcodes and
barcode readers, or in addition thereto, one or both of the
connector halves 13, 15 may include a radio frequency
identification (RFID) tag or chip that, in a manner that should be
understood by those of ordinary skill in the art, uniquely
identifies the connector and/or connector halves. An RFID tag
reader may be utilized, in a manner that should be understood by
those of ordinary skill in the art, to "read" the RFID tag. The
reader may then transmit the identifying information to the
controller 11a to be utilized in a similar manner as the
information provided by the barcodes and barcode reader. One
difference between barcoding and using RFID tags is that barcoding
requires a line-of-sight between the barcode and the barcode
reader, and the environmental conditions must be suitable for the
reader to read the barcode, e.g., sufficient light, clarity, etc.
Another difference is that the RFID tags use a local power source,
such as a battery. Though currently-known RFID tag power sources
may provide sufficient power to the tag for extended periods of
time, e.g., years, at some point the power source needs to be
replenished/recharged or replaced, or the RFID tag itself replaced.
Thus, as will be appreciated by those of ordinary skill in the art,
in some systems of the invention it may be more advantageous to use
barcodes/barcode readers and in other systems RFID tags/readers. It
should also be understood that yet other types of identification
systems, either currently-known or later developed, may be used to
identify a connector or connector portion.
[0062] The above-described method may enable manufacturing
formulations that include fewer particulates in the final
formulation than what is possible by mere closing of a cap onto an
open formulation-receiving chamber as is done in traditional
aseptic transfer processes. Traditional aseptic transfer processes
often rely on the cleanliness of the manufacturing environment and
the lack of particulates presence in the ambient atmosphere in
which the open receiving chambers are filled (controlled
environment for pharmaceutical production) to reduce contamination
and to maintain sterility.
[0063] The formulation chambers 20 may be closed within the mold or
right after molding under microfiltered laminar airflow that may
contain a very low level of particulates. The closed receiving
chambers 20 may then be sterilized while closed by known methods,
such as, for example, by irradiation. This approach may result in
extremely limited amount of small particles, if any, and germ-free
conditions within the receiving chamber 20 as well as the
manufactured formulation. The resulting formulation may be safer
for patient use than traditional pharmaceutical processing carried
out in a controlled environment. Thus, the method may, in addition
to improving the purity and sterility of the manufactured
formulation, also result in improved quality and consistency of the
resulting formulation when compared to traditional
manufacturing.
[0064] The method and apparatus described herein may thus control
sterile transfer of substances during the manufacture of a
predetermined formulation, the method including a controller
measuring one or more of a timing or a volume of sterile transfer
of the substance to measure a residence time of the substance at
each stage of the transfer process and adjusting one or more of the
timing or the volume of the sterile transfer to manufacture the
predetermined formulation.
[0065] The systems and methods of the invention rely on certain
conditions. First, the connector portions should be properly
connected to avoid leakage and/or ingress of air, microbes or other
contamination. In addition, the connector should be in a position
in which identifier for the connector or connector portion(s)
(e.g., barcode, RFID tag, etc.) can be read or determined (e.g., by
a barcode reader, RFID tag reader, etc.). Further, the flow meter
should be in a position relative to a flow conduit of or in fluid
communication with the connector so that it can accurately measure
the flow therethrough. If any of these conditions are not present,
the system may not properly function or the system may not assure
the resulting formulation.
[0066] Referring to FIGS. 5-8, a cradle or holder 100 can be
utilized to help ensure the above conditions. Cradle 100 has a main
body 105 and a door or cover 110 movable relative to the body 105
between an open position as shown in FIGS. 5 and 6, to a closed
position as shown in FIGS. 7 and 8. In the illustrated embodiment,
the cover 110 is pivotably connected to the main body 105 by hinges
113. In other embodiments, the cover 110 is attached to the body
105 by mechanisms other than hinges, which should be recognized by
those of ordinary skill in the art. In yet other embodiments, the
cover 110 is not fixedly attached to the body 105.
[0067] The main body 105 defines a first interior cavity 120 and a
second interior cavity 125. The first interior cavity 120 is sized
and shaped to receive therein a connector when the connector halves
13, 15 are in the connected position. More specifically, the first
interior cavity 120 defines a length 1201 that permits the
connector to be received in the first cavity 120 only when the
connector halves 13, 15 are in the properly connected. If the
connector halves 13, 15 are not properly connected together, the
overall length of the connector will exceed the length 1201 of the
first interior cavity 120, and the connector will not fit into the
interior cavity. In this regards, the first interior cavity 120
ensures that the connector is properly connected to avoid leakage
of contamination.
[0068] The first interior cavity 120 also contains a reader or
sensor 130 configured to identify the connector and/or connector
halves 13, 15 present in the interior cavity as discussed above. In
some embodiments, the sensor is an RFID tag reader adapted to read
the RFID tag(s) present on the connector. In other embodiments, the
sensor 130 is a barcode reader that is configured to read the
barcode(s) on the connector. When the sensor 130 determines the
identifying information regarding the connector and/or connector
halves 13, 15, it transmits that information to the controller 11a
via wire 130a. In other embodiments, the identifying information is
transmitted wirelessly, as would be understood by those or ordinary
skill in the art. The controller 11a may then use the identifying
information to control fluid flow through the connector, and
according, the formulation process, as described herein. In some
embodiments, wire 130a supplies electrical power to the sensor 130.
In other embodiments, the sensor 130 is locally powered, such as by
a battery.
[0069] The second interior cavity 125 is sized and configured so as
to be able to receive therein a portion of the flow channel 17 of
the connector, e.g., a tube or conduit. The second interior cavity
contains therein a flow meter 140. The flow meter 140 is located
with the second interior cavity 125 and otherwise configured so
that, when the connector is located in the cradle, and thus a
portion of the flow channel 17, the flow meter 140 can measure or
otherwise determine the flow rate of substance through the
connector as described herein. In the illustrated embodiment, the
flow meter 140 transmits its readings to controller 11a via wire
140a. In other embodiments, the cradle 100 is wirelessly enabled in
a manner that should be understood by those of ordinary skill in
the art, for wireless transmission of the flow reading to the
controller 11a. In some embodiments, wire 140a supplies electrical
power to the flow meter 140. In other embodiments, the flow meter
140 is locally powered, such as by a battery.
[0070] As seen in FIGS. 5 and 6, when the cover 110 is in the open
position, the cover 110 does not block ingress or egress of the
connector or the flow channels 17, 18 into or out of the interior
cavities. The connector and a portion of the flow channel 17 may
then be inserted into the cradle, e.g., the first and second
cavities 120, 125, respectively. Once the connector and flow
channel 17 are placed within the cradle 100, the cover 110 may be
closed as shown in FIGS. 7 and 8.
[0071] When the cover 110 is closed, the cover 110 sufficiently
blocks access to the interior cavities 120, 125 so that the
connector and/or flow channel 17 may not be removed from the cradle
100. Thus, the cover 110 help prevent inadvertent removal or
dislodging of the connector and/or flow channel 17 from the first
and second cavities 120, 125, respectively, that may interfere with
the readings of the sensor 130 and/or flow meter 140, and
consequently the operation of the formulation system and/or the
quality and content of the formulation.
[0072] In the illustrated embodiment, the cradle 100 contains a
latching system that releasably retains the cover 110 in the closed
position to help prevent inadvertent opening of the cover 110.
Cover 110 contains a latch 110a that engages the main body 105 to
retain the cover 110 in the closed position. Main body 105 has a
depressible release 105a that, in a known fashion, disengages the
latch 105a from the main body 105 to allow the cover 110 to be
moved toward the open position. Those skilled in the art will
understand that other latching systems alternatively may be
utilized in the invention.
[0073] Referring now to FIGS. 9-11, another embodiment of cradle
200 is shown. Cradle 200 is similar to cradle 100 in a number of
respects, and like elements use like reference numbers, but are
preceded with the numeral "2" instead of the numeral "1" as used in
FIGS. 5-8. Like cradle 100, cradle 200 contains a main body 205 and
a cover 210 that is pivotably connected to the main body 205 via
hinge connection 213. Cradle body 205 defines a first interior
cavity 220 and a second interior cavity 225 for receiving therein a
connector and a flow channel 17, respectively. The first interior
cavity 220 includes a reader or sensor 230 that is configured and
functions similarly to sensor 130 of cradle 100. The second
interior cavity 225 includes a flow meter 240 that is configured
and functions similarly to flow meter 140 of cradle 100. In
addition, embodiments of cradle 200 can include similar safety
and/or interlock features as may cradle 100.
[0074] One way in which cradle 200 differs from cradle 100 is that
instead of defining only one viewing window, body 205 defines three
viewing windows 207a, 207b, 207c. Another way in which cradle 200
differs from cradle 100 is that cradle 200 does not have a latching
mechanism. Other differences between cradle 100 and cradle 200,
including but not limited to the shape and configuration of the
cradles, should be apparent from the figures to those of ordinary
skill in the art.
[0075] FIGS. 12-14 schematically illustrate an exemplary use of the
cradle 200 in a formulation system 1000. In addition to the cradle
200 and the connector (portions 13, 15 and flow channels 17, 18 in
fluid communication thereof), the system 1000 include a pump 1010
including a pumping mechanism configured to pump substance in flow
channel 18 (e.g., a tube or conduit) through the connector and
subsequently along flow channel 17. In the illustrated embodiment,
the pump 1010 is a peristaltic-type pump, as is known. In such
pumps, the pumping mechanism 1020 engages the external surface 18a
of the flow channel 18, and by a sequential compression/squeezing
action by the pumping mechanism 1020 on the external surface 18a,
compresses the substance in the flow channel 18 and thereby pumps
the substance. Peristaltic-type pumps may be used in closed or
intact systems in which the pumped substance does not contact or
become exposed to the ambient atmosphere. No part of the pump 1010
contacts the substance itself in the flow channel 18, reducing risk
of contamination of the substance. In contrast, pumps whose parts
contact the pumped substance must rely on seals to prevent exposure
of the substance to the ambient atmosphere or contaminants from the
ambient atmosphere. Such seals can fail, leading to undesirable
exposure or contamination of the substance.
[0076] In addition, flow channels 17, 18 contain flow control
valves or clips 20, 22, respectively, that can control flow through
the flow channels 17, 18 independently of the operation of the pump
1010. In some embodiments, the flow channels 17, 18 are flexible
tubing. The clips 20, 22 may each be manually adjusted to at least
partially and/or fully crimp or squeeze down the flow channels 17,
18 to restrict or stop flow through a respective flow channel. The
illustrated clips 20, 22 contact only the exterior of the flow
channels 17, 18, so that the clips 20, 22 do not contact the
substance in the flow channels 17, 18, reducing the risk of
contamination of the substance. It should be understood by those of
ordinary skill in the art, though, that the illustrated flow
control valves are merely exemplary, and any suitable valve(s),
that either contact the substance in the flow channels 17, 18 or
not, may be used.
[0077] As seen in FIG. 12, the connector halves 13, 15 have been
connected together forming a fluid path between flow channels 17
and 18 through the connector. The halves 13, 15 can be connected by
various ways. They can be manually connected. The may alternatively
be connected by a connecting device, such as connecting device 16
described above. The cover 210 of the cradle 200 is in the open
position, permitting access to the first and second interior
cavities 220, 225. As seen in FIG. 13, the connector has been
placed into the cradle 200, with the connector located in the first
interior cavity 220, and the flow connector 17 located in the
second interior cavity 225. In addition, the flow channel 18 has
been placed into engagement with the pumping mechanism 1020 of the
pump 1010. Though, as illustrated, the flow channel 18 has been
engaged with the pump, in other embodiments flow channel 17 may be
engaged with the pump 1010. Turning now to FIG. 14, the cover 210
has been moved to the closed position. The connector is accordingly
retained in the cradle 210 for formulation operations and
monitoring and recording by the controller 11a. In some
embodiments, the cover 210 is configured to place a compression
force on the connector and flow channel 17 in the closed position,
so as to further maintain the components in the proper
position.
[0078] The cradle 200 may provide or utilize one or more safety
features or interlocks to help assure that the formulation
processing system does not operate under unfavorable conditions.
More specifically, the cradle 200 may contain systems that ensure
that substance is not transferred though the connector if one or
more desired conditions are not present. For example, sensor 230
may be utilized as a connector presence detector. If the reader 230
does not or cannot read the barcode(s), RFID tag(s), or other
identifier(s) of a connector, this may indicate that the connector
is not properly positioned in the cradle 200. As described above,
if the connector is not properly positioned in the first interior
cavity 220, a proper connection of the connector halves 13, 15
cannot be verified. In that case, where the sensor does not read or
determine the identifying information, the sensor 230 will not
transmit any identification information to the controller 11a. In
such embodiments, the controller 11a may be programed to determine
that, in the absence of receiving identifying information from the
reader 230, the connector portions 13, 15 may not be properly
connected. In these circumstances, the controller 11a may not
operate the system, e.g., activate the pump 1010, or otherwise
operate the formulation processing a revise manner. Accordingly,
leakage and/or contamination of substance transferred through the
connector can be effectively avoided.
[0079] In other embodiments, the first interior cavity 220 may
contain another or additional presence sensor. In some embodiments,
the presence sensor may be mechanical or electromechanical, such as
a switch that is configured and placed in the cradle so as to be
moved from a first position when the connector is not properly
located in the first interior cavity 220 to a second position when
the connector is properly located in the first interior cavity 220.
In the second position, the switch may transmit a signal to the
controller 11a, which the controller 11a recognizes as indicating
that the connector is properly located in the first interior cavity
220. In the first position, the switch may transmit a signal to the
controller 11a that the controller 11a recognizes as indicating
that the connector is not properly located in the first interior
cavity 220. Alternatively, in the first position, the switch may
transmit no signal to the controller 11a, which the controller 11a
recognizes as indicating that the connector is not properly located
in the first interior cavity 220. The switch may be biased toward
the first position, e.g., by a spring, so that the default
indication to the controller 11a is that the connector is not
properly present in the cradle 200.
[0080] In other embodiments, the connector presence detector may be
electronic, such as, for example, an "electric eye." As should be
understood by those in the art, an electronic connector presence
detector could operate similarly to the mechanical or
electromechanical detector in that if the detector does not detect
the connector in the proper position in the cradle 200, it may send
a signal or no signal to the controller 11a that the controller
will recognize as indicated that the connector is not properly
positioned in the first interior cavity 220. Conversely, if the
detector detects the connector in the proper position, it may send
a signal to the controller 11a that is recognized as indicating
that the connector is properly positioned in the first interior
cavity 220.
[0081] Those skilled in the art should recognize that other systems
for determining whether the connector is properly located within
the cradle 200. In all these embodiments, though, if the controller
11a does not receive a signal indicating that the connector is
properly located in the first interior cavity 220, or if the
controller 11a ceases to receive such a signal, the controller 11a
may prevent the system from operating, e.g., not operate or shut
down the pump 1010, or otherwise stop or modify the operation of
the formulation system to compensate.
[0082] As seen in FIGS. 9-14, the main body 205 also defines an
opening or viewing windows 207a, 207b, 207c that permits viewing of
the connector in the first interior cavity 220. This permits visual
confirmation of that the connector is properly located within the
first interior cavity. Other embodiments, though, do not have a
viewing window.
[0083] In yet other embodiments, the cradle 200 includes a cover
position detector. The cover position detector detects whether the
cover 210 is in the open position or the closed position. Similar
to the connector presence detector, the cover position detector may
utilize mechanical, electromechanical and/or electronic systems to
determine the position of the cover 210. For example, a switch may
be configured and placed in the cradle 200 so as to be moved from a
first position when the cover 210 is open (or not closed) to a
second position when the cover is in the closed position. In the
first position, the controller 11a receives a signal or receives no
signal from the cradle 200, which the controller 11a recognizes as
indicating that the cover is open or not closed. In the second
position, the controller 11a receives a signal that the cover is
closed. If the controller 11a does not receive a signal that the
cover is closed, the controller 11a may prevent the system from
operating, cease operation of the system, and/or modify system
operation to compensate for that closure of the cover is not
confirmed. The switch may be biased toward the first position,
e.g., by a spring, so that the default indication to the controller
11a is that the cover is in the open position. Accordingly, any
disconnection of the connector hales 13, 15 would require opening
of the cover and removing the connector from the cradle, one or
both of which events would be recognized and/or recorded by the
controller 11a, which may execute appropriate actions.
[0084] It should be noted that in embodiments where the flow path
of the substance is closed or sealed from the ambient atmosphere,
e.g., the substance does not contact or become exposed to the
ambient atmosphere or environmental contaminants as it flows
through he flow channels 17, 18 and the connectors, the cradles or
holders of the invention may be used in a non-classified
environment. This is accomplished because the substance does not
contacting at the readers, sensors, flow meters and other
components of the cradles. All of the measuring, sensing, reading
and detecting by the cradles is performed externally the connectors
and flow channels 17, 18, preventing contamination of the substance
by such components.
[0085] Accordingly, the invention effectively determines and
assures a proper connection of the sterile connector before
substance is passed through the connector. It also prevents
uncontrolled human intervention and error in the production of a
formulation. Thus, in combination with the aforesaid measurement
and recording of substance transfer, flow timing, and residence
time, by way of example, the invention enables high replication of
product quality and composition among formulation lots, and also
among different producers utilizing congruent formulation systems
and process parameters.
[0086] The flow measurement capabilities of the invention also
enable inventory management. By measuring the amount of ingredients
used, the system can determine when ingredients run low or are
depleted, or will become depleted. The controller 11a can then
adjust the formulation process, e.g., batch size or flow rates of
other ingredients, to prevent a deviation in formulation
composition.
[0087] The invention also permits remote monitoring, inspection and
auditing of the formulation process. The electronic transmission
and recording of data from the sensors and flow meters permits an
operator or auditor to monitor, review or analyze that process
without being on-site at the production facility. This may be done
based on recorded information that is retrieved by the operator. It
may also be performed on a live update or real-time basis, with
current process information sent to the auditor. If the reported
information is within the desired or predetermined parameters, the
auditor can be assured that the formulated product meets the
product specifications. For example, if the flow rates and flow
times of the various ingredients (and thus the ingredient amounts
or relative ingredient amounts) meet the specifications, the
formulated product will meet the specifications. Further, as the
proper connection of the connectors can be verified by the cradle
and recorded by the system, the auditor can be assured that the
product meets quality requirements.
[0088] The invention thus enables the auditor to assess, control
and/or verify that all the connections and the process in general
all comply with requirements of process (according to the checklist
used to assess compliance). Currently, regulations are general in
nature and subject to interpretation by an auditor (e.g., the FDA).
This is a somewhat subjective decision by the auditor, because the
process parameters are presently not recorded. Thus, the auditor
must assess, based on limited information, whether the regulations
are complied with. In contrast, by using the invention, auditors
may remotely determine compliance with regulatory requirements
without an on-site visit, and without making subjective
determinations based on limited information after-the-fact.
[0089] The invention may also be used to detect, mitigate and
prevent errors. In addition to, as discussed above for example,
preventing or modifying operation of the formulation process if a
connector is not confirmed as being in the cradle and thus properly
connected, the controller 11a, for example, compare current
operating parameters against expected or specified operating
parameters. If a deviation is detected, the controller 11a may
modify current operation to return or maintain the product
formulation to specification. For example, the controller can be
configured (e.g., programmed) to compare measured ingredient flow
rates against expected flow rates. If a deficiency in ingredient
flow (low or lack of flow) is detected, or higher than expected
flow rates are detected, the controller may take actions to
compensate for such. The controller 11a may increase or decrease
connector connection time so compensate for the deviation in flow
rate so as to maintain the amount of ingredient being transferred
within specification. Controller 11a may also, for example, change
the operating speed of the pump 1010.
[0090] On the other hand, if the process cannot be modified by the
controller 11a to maintain the product specifications, the
controller may generate an error signal to an operator or auditor,
or stop the formulation process. In the instance where the auditor
is a regulatory entity, such as the FDA, the entity can take
immediate action, e.g., prohibit the sale of the product or
initiate a recall, rather than do so retrospectively after the
product has been distributed or used.
[0091] As may be recognized by those of ordinary skill in the
pertinent art based on the teachings herein, numerous changes,
modifications and improvements may be made to the above-described
and other embodiments of the present invention without departing
from the scope of the invention as defined in the appended claims.
It should be understood that the features disclosed herein can be
used in any combination or configuration, and is not limited to the
particular combinations or configurations expressly specified or
illustrated herein. Thus, in some embodiments, one or more of the
features disclosed herein may be used without one or more other
feature disclosed herein. In some embodiments, each of the features
disclosed herein may be used without any one or more of the other
features disclosed herein. In some embodiments, one or more of the
features disclosed herein may be used in combination with one or
more feature that is disclosed (herein) independently of said one
or more features. In some embodiments, each of the features
disclosed (herein) may be used in combination with any one or more
feature that is disclosed herein independently of said one or more
features.
[0092] In addition, the invention may be used in conjunction with
the disclosures of the following U.S. Patent applications, each of
which is incorporated herein by reference: U.S. patent application
Ser. No. 15/410,513, filed Jan. 19, 2017, entitled "Apparatuses and
Methods for Formulating Using a Swirl Chamber," which claims
priority to similarly-titled U.S. Provisional Patent Application
No. 62/280,691, filed Jan. 19, 2016; U.S. patent application Ser.
No. 15/410,762, filed Jan. 19, 2017, entitled "Single Use
Connectors," which claims priority to similarly-titled U.S.
Provisional Patent Application No. 62/280,693, filed Jan. 19, 2016;
U.S. patent application Ser. No. 15/410,740, filed Jan. 19, 2017,
entitled "Pouch with Fitment and Method of Making Same," which
claims priority to U.S. Provisional Patent Application No.
62/295,139, filed 14 Feb. 2016, U.S. provisional patent application
Ser. No. 62/298,214, filed 22 Feb. 2016, and U.S. provisional
patent application Ser. No. 62/323,561, filed 15 Apr. 2016, each of
which is entitled "Pouch With Over-Molded Fitment And Method Of
Making Same," and U.S. Provisional Patent Application No.
62/280,700, filed 19 Jan. 2016, entitled "Pouch with Heat-Sealed
External Fitment." Accordingly, this detailed description of
currently preferred embodiments is to be taken in an illustrative,
as opposed to a limiting sense.
* * * * *