阅读说明：本技术 用于药物容器的填充-整理承载件 (Filling and collating carrier for medicament containers ) 是由 A·M·A·德切莱特 S·R·德维特 R·G·小杰特 L·劳伦斯 M·A·德斯特法诺 于 2017-06-06 设计创作，主要内容包括：一种填充-整理药筒,包括承载件、流体通路连接件、针插入机构和药物容器。这些药筒使得能够使用标准填充设备和过程系统来用药品治疗物填充药物容器,同时保持流体通路的无菌性和容器完整性。本发明的填充-整理药筒可以嵌套或可移除地容纳在填充-整理托盘中,以在标准操作过程中进行批量填充。因而,本发明的自适应填充-整理药筒可以柔性地插入、附接、安装或以其他方式可移除地定位在填充-整理托盘中。因此,这些实施例可以提供易于整合到药物填充过程中的新颖且成本有效的组件和药筒。还提供了组装、制造和使用的方法。(A fill-sort cartridge includes a carrier, a fluid pathway connection, a needle insertion mechanism, and a drug container. These cartridges enable the use of standard filling equipment and process systems to fill drug containers with drug treatments while maintaining sterility of the fluid pathway and container integrity. The fill-collation cartridge of the present invention may be nested or removably received in a fill-collation tray for batch filling during standard operations. Thus, the adaptive fill-collation cartridge of the present invention may be flexibly inserted, attached, installed, or otherwise removably positioned in a fill-collation tray. Thus, these embodiments may provide a novel and cost-effective assembly and cartridge that is easy to integrate into a drug filling process. Methods of assembly, manufacture, and use are also provided.)

1. A cartridge for use in a medicament filling and organizing process, the cartridge comprising:

a medicament container defining a longitudinal axis,

a needle insertion mechanism comprising a needle;

a fluid pathway connection coupled to the drug container;

a flexible sterile fluid conduit fluidly coupled to the needle insertion mechanism and the fluid pathway connection; and

a carrier comprising an upper carrier and a lower carrier;

wherein the lower carrier comprises one or more retention features that engage with the drug container to removably mechanically couple the drug container, the fluid pathway connector, and the needle insertion mechanism.

2. The cartridge of claim 1, wherein the upper carrier comprises an engagement portion configured to allow the tubular body of the upper carrier to be separated from the retention sleeve of the upper carrier.

3. The cartridge of claim 1, wherein the engagement portion comprises one or more frangible tabs.

4. A cartridge as in claim 1, wherein the lower carrier defines a lower carrier cavity, the needle insertion mechanism and the fluid pathway connection being at least partially disposed within the lower carrier cavity.

5. A cartridge according to claim 1, wherein the upper carrier defines an upper carrier cavity, the medicament container being at least partially disposed within the upper carrier cavity.

6. The cartridge of claim 1, wherein the upper carrier comprises one or more connection prongs and the lower carrier comprises one or more connection recesses, the connection prongs being at least partially disposed within the connection recesses to mechanically couple the upper carrier and the lower carrier.

7. The cartridge of claim 6, wherein the upper carrier is decoupled from the lower carrier by rotation of the upper carrier relative to the lower carrier to release the connecting prongs from the connecting recesses.

8. The cartridge of claim 1, wherein the lower carrier comprises a first lower carrier and a second lower carrier, the first lower carrier connected to the second lower carrier to removably mechanically couple the fluid pathway connection and the needle insertion mechanism.

9. The cartridge of claim 8, wherein disconnection of the first lower carrier and the second lower carrier mechanically decouples the fluid pathway connection from the needle insertion mechanism.

10. The cartridge of claim 1, further comprising a pierceable seal disposed in a distal end of the drug container.

11. The cartridge of claim 1, further comprising a fluid contained within the drug container, and a plunger seal disposed within the drug container adjacent a proximal opening of the drug container.

12. The cartridge of claim 1, wherein the upper carrier comprises a flange at a proximal end of the upper carrier.

13. The cartridge of claim 1, wherein the one or more retention features engage with a neck of the drug container.

14. The cartridge of claim 1, wherein the one or more retention features engage with a crimp collar of the drug container.

15. A cartridge for use in a medicament filling and organizing process, the cartridge comprising:

a medicament container defining a longitudinal axis,

a needle insertion mechanism comprising a needle;

a fluid pathway connection coupled to the drug container;

a flexible sterile fluid conduit fluidly coupled to the needle insertion mechanism and the fluid pathway connection; and

a carrier comprising an upper carrier and a lower carrier;

wherein the drug container, the fluid pathway connection and the needle insertion mechanism are removably mechanically coupled by the carrier, and wherein the upper carrier comprises an engagement portion configured to allow the tubular body of the upper carrier to be separated from the retention sleeve of the upper carrier.

16. The cartridge of claim 15, wherein the engagement portion comprises one or more frangible tabs.

17. The cartridge of claim 15, wherein the lower carrier comprises one or more retention features that engage with a neck of the drug container.

18. The cartridge of claim 15, wherein the lower carrier comprises one or more retention features that engage with a crimp cap of the drug container.

19. A cartridge as defined in claim 15, wherein the lower carrier defines a lower carrier cavity, the needle insertion mechanism and the fluid pathway connection being at least partially disposed within the lower carrier cavity.

20. A cartridge according to claim 15, wherein the upper carrier defines an upper carrier cavity, the medicament container being at least partially disposed within the upper carrier cavity.

21. The cartridge of claim 15, wherein the upper carrier comprises one or more connection prongs and the lower carrier comprises one or more connection recesses, the connection prongs being at least partially disposed within the connection recesses to mechanically couple the upper carrier and the lower carrier.

22. The cartridge of claim 21, wherein the upper carrier is decoupled from the lower carrier by rotation of the upper carrier relative to the lower carrier to release the connecting prongs from the connecting recesses.

23. A cartridge as in claim 15, wherein the lower carrier comprises a first lower carrier and a second lower carrier, the first lower carrier connected to the second lower carrier to removably mechanically couple the fluid pathway connection and the needle insertion mechanism.

24. The cartridge of claim 23, wherein disconnection of the first lower carrier and the second lower carrier mechanically decouples the fluid pathway connection from the needle insertion mechanism.

25. The cartridge of claim 24, further comprising a pierceable seal disposed in a distal end of the drug container.

26. The cartridge of claim 15, further comprising a fluid contained within the drug container, and a plunger seal disposed within the drug container adjacent a proximal opening of the drug container.

27. The cartridge of claim 15, wherein the upper carrier comprises a flange at a proximal end of the upper carrier.

28. A method of constructing a cartridge for use in a medicament filling and organizing process, the method comprising the steps of:

fluidly coupling a fluid pathway connection to a needle insertion mechanism;

removably mechanically coupling the fluid pathway connection and the needle insertion mechanism by disposing the fluid pathway connection and the needle insertion mechanism in a lower carrier cavity of a lower carrier;

connecting an upper carrier to the lower carrier; and

a drug container is disposed within the upper carrier cavity of the upper carrier and the drug container is engaged with the one or more retention features of the lower carrier.

29. The method of claim 28, wherein the removably mechanically coupling step comprises connecting a first portion of the lower carrier and a second portion of the lower carrier.

30. The method of claim 28, wherein the connecting step comprises engaging one or more connecting prongs of the upper carrier with one or more medial recesses of the lower carrier.

31. The method of claim 28, further comprising the step of filling the drug container with a fluid.

32. The method of claim 31, further comprising the step of placing a plunger seal within the medicament container adjacent the proximal opening of the medicament container.

33. The method of claim 28, wherein the disposing step comprises engaging a neck of the drug container with one or more retention features of the lower carrier.

34. The method of claim 28, wherein the disposing step comprises engaging a crimp cap of the drug container with one or more retention features of the lower carrier.

35. A method of deconstructing a cartridge for use in a medicament filling and organizing process, the method comprising the steps of:

decoupling the tubular body of the upper carrier from the retention sleeve of the upper carrier;

disconnecting the retention sleeve of the upper carrier from the lower carrier; and

the fluid access connector is mechanically decoupled from the needle insertion mechanism by removing the fluid access connector and the needle insertion mechanism from the lower carrier cavity of the lower carrier.

36. The method of claim 35, wherein the disconnecting step comprises rotating the upper carrier relative to the lower carrier.

37. The method of claim 36, wherein rotating the upper carrier relative to the lower carrier disengages one or more connecting prongs of the upper carrier from one or more connecting recesses of the lower carrier.

38. The method of claim 35, wherein the step of mechanically decoupling comprises separating a first portion of the lower carrier from a second portion of the lower carrier.

Technical Field

The present invention relates to a fill-and-finish cartridge for use in a pharmaceutical fill-and-finish process. More particularly, embodiments of the present invention relate to fill-and-order cartridges that include a carrier (carrier) that enable the filling and ordering of drug containers in a standard fill-and-order process. Methods for manufacturing and filling such cartridges and methods of using the same are also provided.

Background

Parenteral delivery (i.e., delivery other than through the digestive tract) of various drugs has become a desirable method of drug delivery for a variety of reasons. This form of drug delivery by injection can enhance the effect of the delivered substance and ensure that the unaltered drug reaches its intended site in significant concentration. Similarly, unwanted side effects associated with other routes of delivery, such as systemic toxicity, can potentially be avoided by parenteral delivery. By bypassing the digestive system of a mammalian patient, degradation of the active ingredient by catalytic enzymes in the digestive tract and liver can be avoided and the desired amount of drug is ensured to reach the target site at the desired concentration.

Traditionally, manually operated syringes and injection pens have been used to deliver parenteral drugs to patients. More recently, parenteral delivery of liquid drugs into the body has been accomplished by bolus injection (bolus injection) using a needle and reservoir, continuously by gravity-driven dispensers, or via transdermal patch technology. A bolus is often not exactly matched to the clinical needs of the patient and often requires an individual dose that is larger than the desired dose given at a particular time. Continuous delivery of drugs by gravity-fed systems compromises the mobility and lifestyle of the patient, and limits treatment to simplified flow rates and distribution. Similarly, another form of drug delivery (transdermal patch) has its limitations. Transdermal patches generally require a specific molecular drug structure for therapeutic efficacy and control of drug delivery through transdermal patches is severely limited.

Ambulatory infusion pumps have been developed for delivering liquid medicaments to patients. These infusion devices are capable of providing complex fluid delivery profiles that achieve bolus requirements, continuous infusion, and variable flow rate delivery. These infusion capabilities generally result in better efficacy of the drug and therapy, as well as less toxicity to the patient system. Currently available ambulatory infusion devices are expensive, difficult to program and prepare for infusion, and tend to be bulky, heavy, and very fragile. Filling these devices can be difficult and require the patient to carry the intended medication and fill the fitment. These devices typically require specialized care, maintenance, and cleaning to ensure proper functionality and safety for their intended long-term use, and are not cost-effective for patients or healthcare providers.

Pump delivery devices may be significantly more convenient for the patient than syringes and injection pens, as the dose of medication may be automatically calculated and delivered to the patient at any time of day or night. Further, when used in conjunction with a metabolic sensor or monitor, the pump may be automatically controlled to provide the appropriate dosage of fluid medium at the appropriate time as needed based on the sensed or monitored metabolic level. Accordingly, pump delivery devices have become an important aspect of modern medical treatment of various medical conditions such as diabetes and the like.

While pump-type delivery systems have been used to address many patient needs, manually operated syringes and injection pens are still generally the preferred choice for drug delivery because they now provide integrated safety features and can be easily read to identify the status of the drug delivery and the end of dose dispensing. However, manually operated syringes and injection pens are not universally applicable and are not preferred for the delivery of all medications. There remains a need for an adjustable (and/or programmable) infusion system that is accurate and reliable and that can provide clinicians and patients with a small, low cost, lightweight, easy-to-use alternative for parenteral delivery of liquid drugs.

There is a strong market need for a drug delivery device that is easy to use, cost effective and includes an integrated safety feature. However, the manufacture of such devices can be cost intensive, which results in higher costs for the patient. Many manufacturing costs may be attributed to the need to maintain a sterile fluid path from the drug container to the needle prior to introducing the drug into the patient. Some commercial products seek to maintain the sterility of the device by manufacturing the components in a non-sterile environment and then sterilizing the entire device. A recognized disadvantage of such processes is the need to separately fill the drug container after sterilization of the device but prior to drug injection, as most drug compounds cannot withstand the device sterilization process. Alternatively, the drug delivery device may be manufactured as a pre-filled device, wherein the device is aseptically filled with the drug during assembly. Such manufacturing processes can be expensive because the entire process must be kept sterile, and because filling and assembly lines need to be specifically tailored to the device. This therefore adds significant operational costs to pharmaceutical companies and contract drug fillers.

Drug delivery devices are typically prepared by molding or shaping the different components and then assembling the components. The assembly steps and other processing operations typically result in a device that must then be cleaned to remove particulates that adhere to the surface to meet cleanliness standards for drug delivery devices. After cleaning, conventional drug delivery devices are packaged and sterilized. Such delivery devices have been classified into several general types. The first type is assembled and placed in a sterile package that can be shipped with a vial or ampoule of drug or other injectable solution. Vials or ampoules are typically made of glass or other transparent material that does not interfere with the stability of the drug during long term storage. The delivery device is filled with a drug or other solution and infused into the patient at the time of use. These devices have the following disadvantages: increasing the time and difficulty of filling the device in use while increasing the likelihood of contamination of the delivery device and/or the drug solution. When the ampoule is opened, there is a further risk that glass particles from the ampoule contaminate the drug solution.

Several of these disadvantages are overcome by providing a pre-filled delivery device that can be filled with a suitable drug solution prior to use. As that term is known in the art, a pre-filled delivery device is a device that is filled by a drug manufacturer and shipped in a ready-to-use condition to a healthcare provider or self-administered patient. Pre-filled delivery devices have the advantage of convenience and ease of application while reducing the risk of contamination of the drug solution. Pre-filled drug delivery devices are typically assembled and packaged in clean rooms to maintain a suitable level of cleanliness. Clean rooms are equipped with large scale filter assemblies and air management systems to remove particulates and pyrogens from the air in the room and to prevent particulates and pyrogens from entering the room. Operators and other personnel in the clean room must wear appropriate protective clothing to reduce contamination of the air and the drug delivery device being manufactured or assembled. As personnel and equipment enter and exit the clean room, the risk of contamination and the introduction of foreign particles and pyrogens increases. The different operations enable the formation of a clean and sterile drug delivery device. However, subsequent handling, filling and printing of the drug delivery device may contaminate the device. Such conventional drug delivery devices must then be cleaned and sterilized prior to use. Accordingly, there remains a need in the industry for an improved system for manufacturing and assembling clean and sterile medical devices and filling such devices.

Disclosure of Invention

The inventors of the present invention have developed fill-and-finish cartridges that utilize a carrier to enable filling of drug containers with drug treatments using standard filling equipment and systems. This advantage is achieved by the novel fill-and-order cartridges of the present invention that are used to allow drug containers to be nested, mounted, or otherwise removably inserted into a tray for a standard fill-and-order process, as discussed further below.

The novel fill-collation cartridges of the present invention are particularly adaptable to medicament containers so that they can be filled with a medical treatment in a standard manufacturing fill-collation line while maintaining sterility of the fluid pathways and container integrity. In conjunction with a drug container, the fill-collation cartridge of the present invention may be nested or removably received in a fill-collation tray for batch filling during standard operations. Thus, the adaptive fill-and-collate cartridge and drug container of the present invention may be flexibly inserted, attached, mounted, or otherwise removably positioned in a fill-and-collate tray. Thus, these embodiments may provide a novel and cost-effective assembly and cartridge that is easy to integrate into a drug filling process.

In a first embodiment, the present invention provides a fill-and-order cartridge including a medicament container to contain a medicament fluid prior to initiation of an injection. For example, the drug container may be a glass vial sealed with a pierceable septum that may be pierced by a user-actuated fluid pathway connection. In at least one embodiment, the drug container is a glass barrel having a pierceable septum seal at a distal end and a plunger seal, such as an elastomeric plunger seal, at a proximal end. Upon activation, the fluid pathway connection may be caused to pierce the drug container, thereby permitting fluid to flow from the container through the connection, fluid conduit, and needle insertion mechanism to deliver the drug to the patient. The fluid pathway connection may also be made of one or more components. In at least one embodiment, the fluid pathway connection includes means for mounting to the drug container, means for connecting the fluid conduit to the drug container, and optionally means for disconnecting the fluid conduit from the drug container. The means for mounting may be, for example, a connection collar. The means for connecting the fluid conduit to the drug container may be, for example, a needle or cannula. The means for disconnecting the fluid conduit may be, for example, a secondary retraction mechanism or a closure flange. The fluid pathway assembly may be installed into a drug delivery device that may include other components to facilitate activation of the device and the needle insertion, retraction and other components of the fluid pathway assembly and the entire device. For example, the device may include a drive mechanism connected to the plunger seal of the drug container to force drug fluid out of the container through the connector, the fluid conduit and the needle insertion mechanism to deliver the drug to the patient. Many different drive mechanisms and other known components may be utilized in this manner, as will be appreciated by one of ordinary skill in the art.

A drug or drug treatment may be filled into the drug container. For example, the drug container may be configured for a pre-filled drug delivery system. In one such configuration, the drug container will have a pierceable seal at the distal end and a plunger seal at the proximal end. The pierceable seal may be fixedly attached to the distal end of the container by gluing or other known bonding or connecting methods, such as compression fitting. The container may then be filled with a desired amount of medicament at the proximal end of the container. After filling is complete, the plunger seal may be mounted at the proximal end of the container. As will be appreciated by those of ordinary skill in the art, this filling and assembly process may be accomplished under vacuum and/or sterile conditions to facilitate the sterile manufacture of the drug container. These drug containers are configured so as to be easily manufactured individually or in groups, as is the case in tray-based filling processes. The integration of a fluid pathway assembly into such a standard fill-and-finish process is accomplished, at least in part, by the novel fill-and-finish cartridge of the present invention.

Accordingly, in another embodiment, the present invention is directed to a fill-and-order cartridge comprising a carrier and a medicament container. As described in further detail below, the carrier may be one or more pieces such that the carrier is expandable or adjustable. Additionally, the carrier may comprise a flange at the proximal end of the medicament container. The flange may be a fixed flange or a removable flange. The flange may be composed of a variety of known materials including, but not limited to, glass and plastic. The carrier serves to retain the drug container in a sterile condition while allowing easy integration of the drug container into a standard fill-and-finish process. The fill-and-finish cartridge may be integrated into a standard tray. For example, these cartridges, assemblies, and containers may be removably mounted into standard fill trays for filling in automated assembly and drug fill lines. These containers may then be filled with the pharmaceutical drug or therapeutic and then sealed by inserting the plunger seal into the proximal end of the drug container.

In yet another embodiment, the present invention is directed to a method of assembling a fill-and-order cartridge that includes the step of mounting a carrier to a medicament container. The manufacturing method may further include the steps of: filling the drug container from an opening at the proximal end; and then movably sealing the proximal end of the medicament container by inserting a plunger seal.

In another embodiment, the invention relates to a method of using a fill-and-order cartridge, the method comprising the steps of: filling the drug container with a drug substance; mounting a needle insertion mechanism to a first location of a drug delivery device; mounting the drug container to a second location of the drug delivery device; activating a fluid pathway connection to pierce a permeable seal at a distal end of a drug container; triggering a needle insertion mechanism to insert the cannula into the patient; the drive mechanism is activated to force the drug substance out of the drug container and through the main container connection, the fluid conduit and the cannula of the needle insertion mechanism to dispense the drug substance into the patient. After completion of drug delivery, the method of use may further comprise the steps of: the needle insertion mechanism is triggered to retract the cannula from the patient. The cannula may be a rigid needle, a flexible tube cannula, or many other known catheters for injection and/or drug delivery.

One embodiment of the present disclosure includes a cartridge for use in a medicament filling and organizing process, the cartridge comprising: a medicament container defining a longitudinal axis; a needle insertion mechanism comprising a needle; a fluid pathway connector coupled to the drug container; a flexible sterile fluid conduit fluidly coupled to the needle insertion mechanism and the fluid pathway connector; and a carrier comprising an upper carrier and a lower carrier; wherein the lower carrier comprises one or more retention features that engage with the drug container to removably mechanically couple the drug container, the fluid pathway connector, and the needle insertion mechanism.

In at least one embodiment, the upper carrier comprises an engagement portion configured to allow the tubular body of the upper carrier to be separated from the retention sleeve of the upper carrier. Optionally, the joint comprises one or more frangible tabs.

In at least one embodiment, the lower carrier defines a lower carrier cavity, the needle insertion mechanism and the fluid pathway connector being at least partially disposed within the lower carrier cavity. Additionally, in at least one embodiment, the upper carrier defines an upper carrier cavity, the medicament container being at least partially disposed within the upper carrier cavity.

In at least one embodiment, the upper carrier comprises one or more connecting prongs and the lower carrier comprises one or more connecting recesses, the connecting prongs being at least partially arranged within the connecting recesses to mechanically couple the upper carrier and the lower carrier. Optionally, the upper carrier is uncoupled from the lower carrier by rotation of the upper carrier relative to the lower carrier to release the connecting prongs from the connecting recesses.

In at least one embodiment, the lower carrier includes a first lower carrier and a second lower carrier, the first lower carrier connected to the second lower carrier to removably mechanically couple the fluid pathway connector with the needle insertion mechanism. Optionally, disconnection of the first lower carrier and the second lower carrier mechanically decouples the fluid pathway connector from the needle insertion mechanism.

In one embodiment, the cartridge comprises a pierceable seal arranged in the distal end of the medicament container. The cartridge also includes a fluid contained within the medicament container, and a plunger seal disposed within the medicament container adjacent the proximal opening of the medicament container.

In one embodiment, the upper carrier comprises a flange at a proximal end of the upper carrier.

In one embodiment, the one or more retention features engage with a neck of the drug container. Alternatively, the one or more retention features engage with a crimp collar of the drug container.

In another embodiment, the cartridge comprises: a medicament container defining a longitudinal axis; a needle insertion mechanism comprising a needle; a fluid pathway connector coupled to the drug container; a flexible sterile fluid conduit fluidly coupled to the needle insertion mechanism and the fluid pathway connector; and a carrier comprising an upper carrier and a lower carrier; wherein the drug container, the fluid pathway connector and the needle insertion mechanism are removably mechanically coupled by the carrier, and wherein the upper carrier comprises an engagement portion configured to allow the tubular body of the upper carrier to be separated from the retention sleeve of the upper carrier.

The present disclosure also includes a method of constructing a cartridge for use in a medicament filling and organizing process, the method comprising the steps of: fluidly coupling a fluid pathway connector to a needle insertion mechanism; removably mechanically coupling the fluid pathway connector and the needle insertion mechanism by disposing the fluid pathway connector and the needle insertion mechanism in a lower carrier cavity of a lower carrier; connecting an upper carrier to the lower carrier; and disposing a drug container within the upper carrier cavity of the upper carrier and engaging the drug container with the one or more retention features of the lower carrier.

The method of constructing may further comprise connecting the first portion of the lower carrier and the second portion of the lower carrier. The method may further comprise engaging one or more connecting prongs of the upper carrier with one or more intermediate recesses of the lower carrier. The method may further comprise filling the drug container with a fluid. The method may further comprise the step of placing the plunger seal within the medicament container adjacent the proximal opening of the medicament container. The method may also include engaging the neck of the drug container with one or more retention features of the lower carrier. The method may also include engaging a crimp cap of the drug container with one or more retention features of the lower carrier.

Another embodiment of the invention comprises a method of deconstructing a cartridge for use in a medicament filling and organizing process, the method comprising the steps of: decoupling the tubular body of the upper carrier from the retention sleeve of the upper carrier; disconnecting the retention sleeve of the upper carrier from the lower carrier; and mechanically decoupling the fluid pathway connector from the needle insertion mechanism by removing the fluid pathway connector and the needle insertion mechanism from the lower carrier cavity of the lower carrier.

The deconstruction method may further comprise rotating the upper carrier relative to the lower carrier. Rotation of the upper carrier relative to the lower carrier may disengage one or more connecting prongs of the upper carrier from one or more connecting recesses of the lower carrier. In one embodiment, the method comprises separating the first portion of the lower carrier from the second portion of the lower carrier.

In this specification, unless otherwise indicated, "comprises" or "comprising" or related terms, such as "comprises" or "comprising," are used in an inclusive, but not exclusive, sense such that a stated integer or group of integers may include one or more other unstated integers or groups of integers. As will be described further below, embodiments of the present invention may include one or more additional components that may be considered standard components in the medical device industry. These components, and embodiments incorporating such components, are within the contemplation of the present invention and should be understood to fall within the breadth and scope of the present invention.

Drawings

The following non-limiting embodiments of the present invention are described herein with reference to the following drawings, in which:

FIG. 1 is an isometric view of a drug delivery device incorporating an embodiment of a drug container and fluid pathway of the present invention;

fig. 2 is a schematic representation of an exemplary fill-and-collate cartridge of the present invention;

fig. 3 is an exploded isometric view of a fill-collation cartridge according to an embodiment of the present invention;

fig. 4A and 4B are a cross-sectional view and a front view, respectively, of a lower assembly of a fill-and-collate cartridge in accordance with at least one embodiment;

fig. 5A and 5B are a cross-sectional view and a front view, respectively, of a fill-and-collate cartridge in accordance with at least one embodiment connected to an upper carrier of a lower assembly;

fig. 6A and 6B are a cross-sectional view and a front view, respectively, of a fill-and-collate cartridge in accordance with at least one embodiment of a medicament container disposed within an upper carrier;

fig. 7A and 7B are a cross-sectional view and a front view, respectively, of a fill-and-collate cartridge in accordance with at least one embodiment, wherein the upper carrier is in a locked configuration;

fig. 8A and 8B are a cross-sectional view and a front view, respectively, of a fill-and-finish cartridge that has been filled with a medicament and a plunger seal positioned within a medicament container, in accordance with at least one embodiment;

fig. 9A and 9B are a cross-sectional view and a front view, respectively, of a fill-and-collate cartridge in accordance with at least one embodiment, with the tubular body of the upper carrier removed;

fig. 10A and 10B are a cross-sectional view and a front view, respectively, of a fill-and-collate cartridge in accordance with at least one embodiment, with a retention sleeve of an upper carrier removed;

fig. 11 is a cross-sectional view of a fill-and-finish cartridge with a lower carrier removed in accordance with at least one embodiment;

12A, 12B, and 12C are front, side, and isometric views, respectively, of a lower carrier in accordance with at least one embodiment;

fig. 13 is a front view of an upper carrier in accordance with at least one embodiment;

fig. 14 is an isometric view of an array of fill-and-finish cartridges arranged in a fill-and-finish bucket according to the present invention.

Detailed Description

The inventors of the present invention have developed a cartridge carrier that may enable filling a drug container with a drug treatment using standard filling equipment and systems. This advantage is achieved by the novel fill-and-order cartridges of the present invention which are used to allow drug containers to be nested, mounted or otherwise removably inserted into a tray for a standard fill-and-order process. Thus, the adaptive fill-and-collate cartridge and drug container of the present invention may be flexibly inserted, attached, mounted, or otherwise removably positioned in a fill-and-collate tray. Thus, these embodiments may provide a novel and cost-effective assembly and cartridge that is easy to integrate into a drug filling process. Embodiments of the present invention may be integrated into advanced drug delivery devices that require sterile fluid pathways, such as syringe pumps and/or infusion pumps.

As used herein to describe any relative position of a fluid pathway assembly, a fill-and-order cartridge, a drug delivery device, or a component of the present invention, the terms "axial" or "axially" generally refer to a longitudinal axis "a" about which a drug container is preferably formed but not necessarily symmetrically. The term "radial" generally refers to a direction orthogonal to axis a. The terms "proximal", "posterior", "rearward", "back", or "rearward facing" generally refer to an axial direction in the direction labeled "P" in fig. 3. The terms "distal", "forward", "press down" or "forward" generally refer to an axial direction in the direction labeled "D" in fig. 3. As used herein, the term "glass" should be understood to include other similar non-reactive materials suitable for use in pharmaceutical grade applications where glass would normally be required. The term "plastic" may include both thermoplastic and thermoset polymers. The thermoplastic polymer can be softened again to the original state by heating; thermosetting polymers cannot. As used herein, the term "plastic" refers primarily to moldable thermoplastic polymers, such as polyethylene and polypropylene, or acrylics, which typically also contain other ingredients, such as curatives, fillers, reinforcing agents, colorants, and/or plasticizers, and the like, and which may be formed or molded under heat and pressure. As used herein, the terms "elastomer," "elastic," or "elastomeric material" refer primarily to crosslinked thermoset rubber polymers that are more deformable than plastics, but are approved for use in pharmaceutical grade fluids and are not susceptible to leaching or gas migration. As used herein, the term "fluid" refers primarily to liquids, but may also include suspensions of solids dispersed in liquids, as well as gases dissolved or otherwise present together in liquids within the fluid-containing portion of the syringe.

Turning to fig. 1, a schematic representation of an example of a drug delivery device 10 incorporating aspects of the present invention is shown. The device 10 includes a housing 12 having an activation mechanism 14. The housing 12 is schematically shown for ease of understanding. According to the invention, the device further comprises a medicament container 18. The fluid pathway assembly 20 may include other structures to facilitate the arrangement of various components, including, for example, a fluid conduit 26. The fluid pathway connection 22 is disposed substantially adjacent a distal end 28 of the drug container 18, and the needle insertion mechanism 24 is disposed substantially adjacent a distal end 30 of the fluid pathway connection 22. In the illustrated embodiment, the drug container 18 is generally horizontally positioned and perpendicular to the vertically positioned needle insertion mechanism 24. However, it should be understood that these components may be positioned in any suitable manner.

Administration of the medicament contained in the medicament container 18 may be initiated by activating the mechanism 14. The activation mechanism 14 may comprise an activation mechanism that is manually actuated, such as by a user, or automatically actuated, such as by a power and control module 32, which may include a microprocessor or other automated administration arrangement with appropriate connections, as another example. In this embodiment, the activation mechanism 14 is a button 34 that may be disposed, for example, along an exterior surface of the housing 12 and may be selectively depressed by a user. It should be understood that the drug delivery device 10 and the activation mechanism 14 may have any suitable design.

The power and control module 32 may include a power supply to power various electrical components within the drug pump, one or more feedback mechanisms, a microcontroller, a circuit board, one or more conductive pads, and one or more interconnects. Other components commonly used in such electrical systems may also be included, as will be appreciated by those of ordinary skill in the art. The one or more feedback mechanisms may, for example, include an audible alarm such as a piezoelectric alarm and/or a light indicator such as a Light Emitting Diode (LED). The microcontroller may be, for example, a microprocessor. The power and control module 32 controls several device interactions with the user and may interface with one or more other components of the drug delivery device 10. In one embodiment, power and control module 32 may identify when the on-body sensor and/or activation mechanism 14 is activated. The power and control module 32 may also interface with a status indicator (which may be a transparent or translucent material that allows light transmission) to provide visual feedback to the user. The power and control module 32 may interface with the drive mechanism and/or the integrated sterile fluid pathway connection and the drug container 18 through one or more interconnects to relay status indications to the user, such as start-up, drug delivery, and/or end-of-dose. This status indication may be presented to the user via: haptic feedback, such as vibration; an audible tone, such as by an audible alarm; and/or a visual indicator, such as by an LED. In a preferred embodiment, the control interface between the power and control system and other components of the drug pump are not engaged or connected prior to user activation. This is a desirable safety feature to prevent accidental operation of the drug pump, and may also maintain the energy stored in the power source during storage, transportation, etc.

The power and control module 32 may be configured to provide a plurality of different status indicators to a user. For example, power and control module 32 may be configured such that after the on-body sensor and/or trigger mechanism has been pressed, power and control module 32 provides a ready-to-activate status signal via a status indicator if the device activation check does not provide any errors. After providing the ready-to-fire status signal, and in embodiments with an optional on-body sensor, if the on-body sensor remains in contact with the user's body, the power and control module 32 will power the drive mechanism to begin delivery of the medication therapy through the integrated sterile fluid pathway connection 22 and sterile fluid conduit 28. In a preferred embodiment of the present invention, the insertion mechanism 24 and the drive mechanism may be directly actuated by a user operating the actuation mechanism 14. The integrated sterile fluid pathway connection (i.e., the fluid pathway is closed) is connected by pneumatic and/or hydraulic pressure of the drug fluid within the drug reservoir 18 generated by activation of the drive mechanism, as further detailed herein. During drug delivery, the power and control module 32 is configured to provide a dispense status signal via a status indicator. After the medicament is administered into the user's body and after any additional dwell time is over, to ensure that substantially the entire dose has been delivered to the user, the power and control module 32 may provide a removable status signal via the status indicator. This can be independently verified by the user by observing the drive mechanism and the delivery of the dose of medicament within the medicament container through the window 18 of the pump housing 12. Additionally, the power and control module 32 may be configured to provide one or more alarm signals via the status indicators, such as, for example, alarms indicating a fault or failed operation condition.

Other power and control system configurations may be used with the novel drug pump of the present invention. For example, certain start-up delays may be used during drug delivery. As mentioned above, one such delay optionally included in the system configuration is a dwell time that ensures that substantially all of the medicament dose has been delivered before a completion signal is sent to the user. Similarly, activation of the device may require prolonged depression (i.e., pushing) of the activation mechanism 14 of the drug delivery device 10 prior to activation of the drug pump. Additionally, the system may include a feature that allows the user to respond to the end-of-dose signal and deactivate or power off the drug pump. This feature may similarly require a delayed depression of the activation mechanism to prevent accidental deactivation of the device. Such features provide the desired safety integration and easy-to-use parameters for the drug pump. An additional safety feature may be integrated into the activation mechanism to prevent partial depression and thus partial activation of the drug pump. For example, the activation mechanism and/or power and control system may be configured to cause the device to be fully off or fully on to prevent partial activation. Such features are described in further detail below with respect to other aspects of the novel drug pump.

When included, the power and control module 32 may include a processor (not shown) and a memory component (not shown). The processor may be a microprocessor or other processor as is known in the art. In some embodiments, the processor may be comprised of a plurality of processors. The processor may execute instructions for generating an administration signal and controlling administration of the medicament contained in the medicament container 18. Such instructions may be read into or incorporated into a computer-readable medium, such as a memory component, or provided external to the processor. In alternative embodiments, hard-wired circuitry may be used in place of or in combination with software instructions to implement drug administration. Thus, embodiments are not limited to any specific combination of hardware circuitry and software.

The term "computer-readable medium" as used herein refers to any medium or combination of media that participates in providing instructions to a processor for execution. This medium may take many forms. The memory component may include any form of computer readable media as described above. The memory component may include a plurality of memory components.

The power and control module 32 may be enclosed in a single housing. In an alternative embodiment, the power and control module 32 may include a plurality of components operatively connected and enclosed in a plurality of housings.

The power and control module 32 may be configured to generate the application signal in accordance with user actuation, preprogrammed actuation, or remote actuation. The power and control module 32 may be communicatively coupled to the fill-and-order cartridge 16 and/or separately coupled to the drug container 18, the fluid pathway connection 22, and/or the needle insertion mechanism 24.

In accordance with aspects of embodiments of the present invention, in the illustrated embodiment, actuation of the activation mechanism 14 (where button 34 is depressed) triggers the needle insertion mechanism 24 to inject a needle or cannula into a patient. The integrated sterile fluid pathway connection (i.e., the fluid pathway is closed) is connected by pneumatic and/or hydraulic pressure of the drug fluid within the drug reservoir 18 generated by activation of the drive mechanism, as further detailed herein. Thus, actuation of the activation mechanism 14 results in completion of a drug path from the drug container 18, through the fluid path connector 22, the fluid conduit 26, and the needle insertion mechanism 24, to a patient (not shown). Actuation of the activation mechanism 14 may also cause the drive mechanism to act on structure associated with the medicament container 18 to force fluid through the sterile pathway. In an embodiment of the present invention, the needle insertion mechanism 24 may be triggered upon completion of drug delivery to retract the needle from the patient, giving an explicit end of dose indication. The housing 12 may additionally include, for example, a window through which the drug container 18 may be viewed to confirm drug delivery.

The fill-and-order cartridge of the present invention is comprised of a drug container, a fluid pathway connector, and a needle insertion mechanism. These components are held in alignment by the carrier, allowing the use of the fill-and-finish cartridge in a conventional fill-and-finish process. According to an aspect of the present invention, the drug container 18 is filled prior to assembly into the housing 12 of the drug delivery device 10. In this regard, the drug container 18 is sufficiently robust to withstand the procedures used to sterilize the drug container 18, in some embodiments before filling, and in some embodiments after filling. After the drug container 18 is aseptically filled, it may be positioned within the drug delivery device 10 as desired. Providing the user or clinician with a pre-filled device may simplify the operation of the device and reduce the number of operational steps. Using the fill-and-finish cartridge of the present invention to fill the drug container prior to assembly of the drug container into the drug delivery device eliminates the need for terminal sterilization of the entire device. This potentially reduces the cost or size of the device.

According to another aspect of embodiments of the present invention, various embodiments of the various components of the fill-and-order cartridge 16 may be assembled in various configurations to provide various embodiments of the fill-and-order cartridge 16. The following disclosure, assigned to the assignee of the present disclosure, discloses exemplary structures of individual elements that may be incorporated into the fill-and-collate cartridge 16, and is incorporated herein by reference in its entirety for disclosure herein: U.S. application serial No. 13/600,114; U.S. application serial No. 13/599,727; U.S. application serial No. 13/612,203; U.S. application serial No. 13/796,156; U.S. application serial No. 14/466,403; U.S. application serial No. 15/514,951; international patent application No. PCT/US 2016/017534; and international patent application No. PCT/US 2016/020486.

In various embodiments, the fill-and-finish cartridge 16 may remain axially aligned with components during the fill-and-finish process and when used with the drug delivery device 10. That is, for example, during a fill-and-finish process (such as shown in fig. 2) and when used in a drug delivery device, the needle insertion mechanism 24 may be axially disposed with the remainder of the fill-and-finish cartridge 16. In other embodiments, the fill-and-finish cartridge 16 may remain axially aligned with the components during a fill-and-finish process (such as shown in fig. 2), while the components may remain axially misaligned when used with the drug delivery device 10. For example, as shown in FIG. 1, the needle insertion mechanism 24 is spaced from the fluid pathway connection 22 and the drug container 18 and is arranged in a 90 orientation. In other embodiments, the fill-and-finish cartridge may remain axially misaligned with the components during the fill-and-finish process, but axially aligned when used with the drug delivery device 10. In other embodiments, the fill-and-finish cartridge may remain axially misaligned with the components during the fill-and-finish process and when used with the drug delivery device 10.

Furthermore, a carrier may be provided, as will be explained in more detail below. This carrier may be integrated with the structure of the fill-and-finish cartridge 16 such that it remains around or along at least a portion of the fill-and-finish cartridge 16 in the drug delivery device 10, or it may be fully or partially disposable. The carrier may perform a number of functions, such as maintaining the relative positions of various fill-and-finish cartridge components during assembly, a fill-and-finish process, or other operations performed on the fill-and-finish cartridge or a drug delivery device incorporating the fill-and-finish cartridge; the carrier or a portion of the carrier may be used for the interaction of the fill-and-finish cartridge with the drug delivery device 10, such as for attaching the fill-and-finish cartridge 16 into the drug delivery device 10. The following is a more detailed explanation of various examples of such structures in different configurations; the structures are not intended to be limited to those particular configurations. Rather, the individual arrangements explained are provided as examples of the various possible configurations and structures within the scope of the present disclosure.

Fig. 3 illustrates an exploded view of one embodiment of the fill-and-collate cartridge 16 of the present invention. The fluid access assembly 20 includes a needle insertion mechanism 24 coupled to the fluid access connector 22 by a fluid conduit 26. The proximal end of the needle insertion mechanism 24 is connected to the distal end of a fluid conduit 26 which is connected at its proximal end to the fluid pathway connection 22.

The needle insertion mechanism 24 may have any suitable design as long as sterilization can be performed prior to placing the fill-and-finish cartridge 16 in the drug delivery device. Examples of such needle insertion mechanisms 24 for implants and liquid drugs are disclosed in U.S. applications 13/599,727 and 15/514,951 and international application number PCT/US 2016/017534, which are assigned to the assignee of the present application and are incorporated herein by reference in their entirety for disclosure. It should be noted that the needle insertion mechanism 24 of fig. 3 includes an axial configuration such that an application needle (not visible in fig. 3) extends axially from the distal end of the fill-and-finish cartridge 16 for application. However, it should be understood that a needle insertion mechanism 24 disposed at an angle to the axis of the fluid pathway connection 22 and/or the drug container 18 may alternatively be utilized.

The fluid pathway connector 22 may also have any suitable design as long as sterilization can be performed prior to placing the fill-and-finish cartridge 16 in the drug delivery device. Examples of such fluid pathway connectors 22 are disclosed in U.S. applications 13/612,203, 13/796,156, 14/466,403 and international application PCT/US 2016/020486, which are assigned to the assignee of the present application and are incorporated herein by reference in their entirety for all purposes. In at least some embodiments, the fluid pathway connector includes a piercing member configured to pierce a pierceable seal of the drug container upon activation to establish a fluid flow path from the drug container through the fluid pathway connector, the fluid conduit, and to the needle insertion mechanism for delivery to the patient.

The components of the fluid pathway assembly 20, including the needle insertion mechanism 24, the fluid pathway connection 22, and the fluid conduit 26, are formed of materials that can be sterilized by conventional sterilization techniques and machinery. The fluid conduit 26 may be formed of any suitable material, for example a length of flexible tubing, such as plastic tubing. However, it should be understood that in some embodiments (not shown), the fluid pathway connection 22 and the needle insertion mechanism 24 may be directly attached.

The components of the fluid pathway assembly 20 may be sterilized prior to such connection, or may be connected as a unitary component prior to sterilization. If sterilized prior to such connection, the fluid pathway assembly 20 may include an additional seal at the fluid pathway connection 22, such as a permeable seal (not shown) that may be pierced during assembly or actuation.

The medicament container 18 of this and each embodiment may be of any suitable material and of any suitable shape and size, and may include a seal to maintain the integrity and sterility of the medicament contained therein. For example, the medicament container 18 may be formed of glass, plastic, or other suitable material. The drug container 18 of this and each embodiment may include structure to facilitate handling, installation within a drug delivery device, sterilization, and/or interfacing with other components of the fill-and-order cartridge 16. For example, a flange (not shown) may be provided at any suitable location along the medicament container 16. This flange may be integrally formed with the medicament container 18 or may be a separate element secured to the medicament container. In the illustrated embodiment, the carrier 40 includes a flange 42a to facilitate use in filling-and-collating trays. The medicament container 18 is an elongated, generally annular structure and may include an elongated section 18c, a neck 18d, and a collar 18 e. This allows the overall outer diameter of the medicament container 18 to be substantially the same as the overall outer diameter of the elongate section 18 c. This minimizes the amount of space occupied by the drug container 18 in the drug pump and may allow the overall size of the drug pump to be smaller. This may alleviate the inconvenience to the patient.

To facilitate filling of the primary drug delivery container 18 and administration of the drug from the drug delivery container, the drug container 18 may include openings 18a, 18b at the proximal and distal ends, respectively. To seal the drug container 18, a permeable or pierceable seal 50 may be provided at the distal end of the drug container 18. In this manner, once filled, the medicament contained within the medicament container 18 may be maintained in a sterile environment until such time as the seal 50 is pierced by the fluid pathway connection 22 to complete the fluid pathway. The permeable seal 50 may be of any suitable design and material.

For operational efficiency, the needle insertion mechanism 24 may be coupled to the fluid pathway connection 22, and the fluid pathway connection 22 may be connected to the permeable seal 50, wherein the needle insertion mechanism 24 is maintained in a non-piercing configuration during sterilization, filling, and assembly. In this manner, the fill-and-order cartridge 16 may appear as shown in fig. 7B, wherein the fluid pathway assembly 20 is substantially hidden from the external environment by the carrier 40. Once the drug container 18 is filled with the drug treatment, a plunger seal 19 may be provided in the proximal end of the drug container 18 to provide a closed fill-and-finish cartridge 16. In the illustrated embodiment, a resilient plunger seal 19 is inserted into the proximal end of the medicament container 18. However, it should be understood that other suitable sealing arrangements may be provided.

According to another aspect of the present invention, the fluid pathway assembly may be maintained in a sterile state, and drug containers of each assembly may be aseptically filled with a pharmaceutical compound using procedures similar to those known in the art. After filling the drug container with the pharmaceutical treatment and sealing the container, for example, with the plunger seal 19, the fill-and-finish cartridge 16 may be removed from the sterile filling environment without compromising the sterility or container integrity of the drug container 18, the fluidic assembly pathway 20, or their individual components.

According to another aspect of the invention, embodiments of the invention may enable the drug container to be filled in a standard fill-and-finish process. In this regard, the fill-and-finish cartridge may utilize existing or standardized fill-and-finish equipment. A plurality of drug containers may be removably mounted, fitted, inserted, or otherwise placed in a standard fill-collation tray, such as that illustrated in fig. 14, for filling with a drug treatment. The flange 40a of the carrier 40 may facilitate placement and handling of the carrier 40 and the drug container 18. The flange 40a may be configured to interface with a tray 170 that supports one or more fill-and-finish cartridges during a fill-and-finish process. The tray 170 may include one or more apertures through which the body of the carrier 40 may be inserted, the apertures having a diameter less than the outer diameter of the flange 40 a. Thus, after the body of the carrier 40 is inserted through the body, the flange 40a may rest on and be supported by the tray 170. The fill-and-finish cartridge 116 may then be processed through a fill-and-finish process while supported by the tray 170. The drug container 18 may be filled in an automated assembly and drug filling line and then sealed by inserting a plunger seal into the proximal end of the drug container 18. A fill-collation tray having any configuration or capable of holding any number of containers may be utilized.

The fluid pathway components are connected such that sterility of the fluid pathway from the fluid pathway connection, through the fluid conduit, to the needle insertion mechanism is maintained. These novel fill-and-order cartridges of the present invention serve to maintain the sterility of the fluid pathway assembly and allow them to be nested, mounted, or otherwise removably inserted into a tray for standard fill-and-order processes. As shown in fig. 3, in this embodiment, the carrier 40 may include an upper carrier 42 and a lower carrier 44. The medicament container 18 is typically positioned within the upper carrier. The needle insertion mechanism, catheter and fluid pathway connection are typically positioned within the lower carrier. The upper and lower carriers may optionally be composed of more than one separable part.

The carrier holds the drug container 18, needle insertion mechanism 24, and fluid pathway connection 22 in place such that the central axis of the drug container 18 passes through both the needle insertion mechanism 24 and the fluid pathway connection 22. This alignment allows the cartridge to be positioned in a standard fill-and-finish surface tray, thereby minimizing the changes required to accommodate this cartridge.

One embodiment of a fill-and-order cartridge 16 is shown in fig. 3-11. The embodiment shown therein includes an upper carrier 42 and a lower carrier 44, which includes a first lower carrier 46 and a second lower carrier 48. The lower carrier 44 is configured to engage and position the needle insertion mechanism 24 and the fluid pathway connection 22. In at least one embodiment, the fluid pathway connection 22 is fluidly coupled with the needle insertion mechanism 24 via a fluid conduit 26. The fluid passage connector 22 may be positioned within the pocket 45 (shown in fig. 12A), thereby limiting axial translation of the fluid passage connector 22. In some embodiments, limited movement of the fluid pathway connection 22 is permitted. This limited movement of the fluid pathway connection 22 may allow it to be properly positioned relative to the drug container 18. At least one of the first lower bearing 46 and the second lower bearing 48 may include one or more engagement arms 206, while another portion may include one or more corresponding engagement windows 208 (shown in fig. 12C). The connection of the engagement arms 206 and the engagement windows 208 securely and removably connects the first lower carrier 46 and the second lower carrier 48. In the embodiment shown in fig. 12C, each of the first lower bearing and the second lower bearing has an engagement arm 206 and an engagement window 208 configured to engage a corresponding feature on the other component. The first lower bearing 46 and the second lower bearing 48 may be further maintained in the connected position by the interaction of the upper bearing 42 with the lower bearing 44.

The lower carrier 44 may be further configured to engage with the upper carrier 42. For example, one of the lower carrier or the upper carrier may comprise one or more locking prongs configured to engage corresponding connecting recesses on the opposing component. In the illustrated embodiment, the upper carrier 42 includes one or more coupling prongs 42j configured to engage corresponding coupling recesses 47 of the lower carrier 44. The clevis 42j may be configured as relatively flexible portions that are configured to flex radially outward in response to contact with the lower carrier 44. Upon alignment with the coupling recess 47, the coupling fork 42j can return toward its natural position and engage the coupling recess 47. The clevis 42j and the coupling recess 47 may be configured such that rotation of the upper carrier 42 relative to the lower carrier 44 causes the clevis 42j to disengage the coupling recess 47. This allows the upper carrier 42 to be removed from the lower carrier 44 after the filling-and-collating process is completed. While the illustrated embodiment shows the clevis as an aspect of the upper carrier and the clevis as an aspect of the lower carrier, it is also contemplated that this relationship may be reversed (i.e., the clevis is an aspect of the lower carrier and the clevis is an aspect of the upper carrier).

In addition to the connecting recesses 47, the lower carrier 44 may also comprise one or more intermediate recesses 49, as shown in the illustrated embodiment. These medial recesses are configured to temporarily engage with the coupling prongs 42j during assembly of the fill-and-order cartridge 16, as will be further described herein.

Further, the lower carrier 44 may include one or more features configured to engage the drug container 18. For example, one or more portions of the lower carrier 44 may also include one or more retention features 45. The retention features 45 may be configured to engage the neck 18d, crimp cap 62, and/or collar 18e of the drug container 18. The retention features 45 engage the drug container and limit movement of the drug container relative to the lower carrier 44 and thereby limit movement of the fluid pathway connection 22. Thus, piercing member 22a may be positioned within cavity 50a of pierceable seal 50 of drug container 18. Additionally, a portion of the fluid pathway connection 22 may form a sealing engagement with the pierceable seal 50. Thus, when sterilized, the cavity 50a of the pierceable seal 50 sealed by the fluid pathway connection 22 forms a sterile volume. A portion of piercing member 22a is disposed within the sterile space, thereby maintaining sterility of a portion of piercing member 22 a. The retention feature 45 may be configured to flex radially outward in response to contact with a portion of the drug container 18. When aligned with the neck 18d of the drug container 18, the retention feature 45 may return toward its natural position to engage the drug container 18. The upper carrier 42 may include apertures or reliefs that allow clearance of the retention features 45 to flex radially outward, such as when the clevis 42j engages the medial recess 49.

Alternatively, the retention features may be forced radially inward by interference with the upper carrier 42. In this embodiment, the natural position of the one or more retention features 45 may be such that the drug container 18 may pass within the retention features 45 without displacing them. When the upper carrier 42 is placed in its final position, interference between the upper carrier 42 and the retention features 45 may cause them to flex radially inward to engage the medicament container 18.

Various stages of assembly of one embodiment of the fill-and-collate cartridge are shown in fig. 4A through 11, and additional aspects of the invention will be described with reference to these figures. As shown in fig. 4A, the fluid passage assembly 20 is disposed within the lower carrier 44. In this position, the fluid pathway connection 22 is fluidly coupled to the needle insertion mechanism 24 through the fluid conduit 26. The fluid pathway connection 22 and the needle insertion mechanism 24 are mechanically coupled through the lower carrier 44, thereby maintaining the relative spatial relationship of these components. As shown in fig. 4B, the lower carrier 44 includes a first lower carrier 46 and a second lower carrier 48 connected together to enclose the fluid pathway assembly 20. As shown in fig. 4A and 4B, piercing member 22a may extend from lower carrier 44 such that it may engage a seal of drug container 18, as will be described further herein.

Fig. 5A and 5B illustrate the fill-and-collate cartridge 16 after the upper carrier 42 is initially connected to the lower carrier 44. In this position, the clevis 42j engages the medial concavity 49. This connects the upper carrier 42 to the lower carrier 44 while allowing clearance so that the retention features 45 may be in a position to allow passage of the medicament container 18. In this position, the fill-and-order cartridge 16 is ready for connection to the medicament container 18.

Fig. 6A and 6B illustrate the fill-and-collate cartridge 16 with the drug container 18 inserted. In this position, piercing member 22a is disposed within cavity 50a of pierceable seal 50. Engagement of the retention features 45 with the neck 18d and/or the crimp cap 62 maintains the drug container 18 in a spatial relationship with the fluid pathway connector 22. Optionally, the drug container may include one or more center retainers 64 that engage a portion of the fluid pathway connector 22, thereby further limiting the relative movement of the drug container and the fluid pathway connector. One embodiment of this is shown in fig. 6A. By allowing some movement of the fluid pathway connection 22 within the lower carrier 44, the center retainer 64 is able to engage the fluid pathway connection 22 while allowing for tolerance variations. In other words, the spatial relationship of the drug container 18 to the fluid pathway connection 22 may be determined by the central retainer 64, rather than by the upper carrier 42 or the lower carrier 44. This may ensure that at least a portion of fluid pathway connection 22 is in contact with pierceable seal 50 to maintain sterility of piercing member 22 a.

Fig. 7A and 7B illustrate the fill-and-collate cartridge 16 with the upper carrier 42 in the locked position. As can be seen by comparing fig. 6A with fig. 7A, the upper carrier 42 translates in a distal direction relative to the lower carrier 44. Thus, the coupling fork portion 42j engages the coupling recess 47. In this position, the upper carrier 42 prevents the retention features 45 from being displaced radially outward and locks the retention features 45 in the engaged position. Thus, the drug container 18 cannot be removed from the fill-and-finish cartridge 16. In the configuration shown in fig. 7A and 7B, the fill-and-finish cartridge 16 is ready for processing during the fill-and-finish process. Prior to filling, the assembly 16 may be sterilized using any suitable sterilization process. In one embodiment, the fill-and-finish cartridge is sterilized using a gas sterilization process, such as an ethylene oxide sterilization process. The upper carrier 42 and/or the lower carrier 44 may include one or more windows to enhance the efficacy of the sterilization process and to facilitate assembly. After sterilization, the fill-and-finish cartridge 16 may be placed in a bucket or tray. Alternatively, the components of the fill-and-order cartridge may be sterilized prior to assembly.

Fig. 8A and 8B illustrate the fill-and-finish cartridge 16 after the filling and capping process. The medicine container 18 contains the filled medicament that has been filled through the proximal opening 18 a. A plunger seal 19 has been placed within the medicament container 18 near its open proximal end. Alternatively, a vacuum sealing process may be used to place the plunger seal.

In some cases, it may be necessary to inspect the drug container and the drug contained therein. This inspection may include rotating the drug container to determine the presence of particles contained therein. In order to provide unobstructed viewing of the medicament container, the upper carrier may be removed. Alternatively, as illustrated, the upper carrier 42 may include a tubular body 42e and a locking sleeve 42f that are separable at an engagement portion 42 g. This allows the tubular body 42f to be removed after filling while the locking sleeve 42f remains in place. With the locking sleeve 42f in place, the retention features 45 cannot flex radially outward, and thus they securely retain the drug container 18. This configuration is shown in fig. 9A and 9B. In the illustrated embodiment, the engagement portion 42g is comprised of a frangible tab 42 h. Thus, rotation of the tubular body 42f will break the frangible tabs 42h and allow the tubular body 42f to be removed. Alternatively, other methods may be used to break the frangible tabs 42h, such as applying an axial force to the tubular body 42 e. Although not shown, the engagement portion 42g may alternatively be comprised of any connection means, such as a threaded connection, a press-fit connection, or any other means known to those skilled in the art.

Fig. 10A and 10B illustrate the fill-and-collate cartridge 16 after the locking sleeve 42f is removed. In the illustrated embodiment, the locking sleeve 42f is removed by rotating relative to the lower carrier 44, thereby releasing the coupling fork 42j from the coupling recess 47. Alternatively, the locking sleeve 42f may be comprised of two or more separable parts that can be broken to remove the locking sleeve 42f from the lower carrier 44.

After removal of the locking sleeve 42f, the lower carrier 44 may be removed, thereby mechanically decoupling the fluid pathway connector 22 from the needle insertion mechanism 24. These components remain fluidly coupled by fluid conduit 26. Piercing member 22a remains disposed within cavity 50a, thereby maintaining sterility of piercing member 22 a. As shown in fig. 11, this may be due in part to the center retainer 64 engaging the fluid pathway connection 22. With the carrier 40 removed, the drug container 18, the fluid pathway connector 22, and the needle insertion mechanism 24 may be placed in the drug delivery device 10, as shown in fig. 1. In the illustrated embodiment, the carrier 40 is completely removed and is not included in the drug delivery device 10. However, in other embodiments, one or more aspects of the carrier 40 remain connected to one of the drug container 18, the fluid pathway connection 22, and/or the needle insertion mechanism 24 when inserted into the drug delivery device 10.

Additionally, one or more embodiments facilitate the use of a vacuum seal to position the plunger seal within the drug container 18. By doing so, the amount of air entrained within the medicament container may be significantly reduced. This can be achieved with minimal or no modification to standard fill-and-trim equipment.

To allow the vacuum sealing apparatus to be used with flangeless drug containers, a sealing member (not shown) may be positioned between the drug container 18 and the carrier 40. The sealing member may be, for example, an elastic member such as an o-ring. The sealing member may be located anywhere along the medicament container 18, or alternatively, the sealing member may be in contact with the crimp cap 62. The carrier 40 or the drug container 18 may include grooves, recesses, or other features in which a sealing member may be positioned. In at least one embodiment, a plurality of sealing members are positioned at a plurality of locations within the carrier, which may improve the efficacy of the sealing members. By providing a sealing member between the drug container 18 and the carrier 40, standard vacuum sealing equipment may be used with the fill-and-finish cartridge of the present invention. The sealing element of the closure-placement tube may contact and seal against the flange of the carrier 40. The distal end of the medicament container 18 is closed by a pierceable seal 50. The distal seal may be held in place by a crimp cap 62. Because the carrier 40 is in sealing engagement with the drug container 18 due to the sealing member, a sealed volume is created within the carrier that includes the volume within the drug container 18. Accordingly, a vacuum may be drawn on this volume, thereby reducing the pressure within the drug container 18 and allowing placement of the plunger seal, as previously described with respect to standard vacuum sealing procedures. This provides a simple and cost effective method of placing the plunger seal within the medicament container.

The sealing member may be a separate component, such as an o-ring, or alternatively, the sealing member may be an integral part of one or more components. For example, the elastomeric material may be co-molded with the carrier such that the elastomeric material is in contact with the drug container, crimp cap, or other component during the filling-trimming process.

In an alternative embodiment, a radial seal at the proximal end of the medicament container is used during the vacuum sealing process. To facilitate the use of this radial seal, the proximal end of the drug container 18 may be configured to extend beyond the carrier 40, as shown in fig. 7B. During the capping process, the annular seal may engage this exposed portion of the drug container 18 to allow a vacuum to be created.

In another embodiment, a method of use for handling a medication container may comprise the steps of: sealing the distal opening 18b of the drug container 18, inserting the drug container 18 into the carrier 40, inserting the carrier 40 and the drug container 18 into the tray 170, and filling the drug container 18 with the drug. The method may further include the step of engaging the retention feature 45 with the neck 18d and/or collar 18e of the drug container 18. The method may further include the step of inserting a seal into the proximal end of the drug container 18 to thereby seal the contents of the drug container 18. As one of ordinary skill in the art will appreciate, this filling and assembly process may be accomplished under vacuum and/or sterile conditions. The medicament containers are configured such that they can be easily manufactured individually or in groups, as is the case in tray-based filling processes.

In another embodiment, the present invention relates to a method of using a fill-and-order cartridge, which may include the steps of: filling the drug container with a drug substance; mounting a needle insertion mechanism to a first location of a drug delivery device; mounting the drug container to a second location of the drug delivery device; activating a fluid pathway connection to pierce a permeable seal at a distal end of a drug container; triggering a needle insertion mechanism to insert the cannula into the patient; the drive mechanism is activated to force the drug substance out of the drug container and through the main container connection, the fluid conduit and the cannula of the needle insertion mechanism to dispense the drug substance into the patient. After completion of drug delivery, the method of use may further comprise the steps of: the needle insertion mechanism is triggered to retract the cannula from the patient. The cannula may be a rigid needle, a flexible tube cannula, or many other known catheters for injection and/or drug delivery.

The novel medicament container and carrier of the present invention may provide great benefits in the marketplace. Embodiments of the present invention may be easily manufactured in an aseptic environment, integrated in a standard filling (e.g., fill-and-order) production line for aseptically filling pharmaceutical treatments, and used for assembly into drug delivery devices in a cost-effective manner. Each of these advantages has great benefits over existing approaches.

Furthermore, embodiments of the present invention allow for filling of drug containers using standard fill-and-finish procedures. This greatly simplifies the manufacturing process for constructing the drug delivery device. A standard fill-and-order process utilizes a tray that holds a plurality of medication containers, such as syringes. Embodiments of the present invention enable a drug delivery device manufacturer, pharmaceutical company, or contract drug filler to fill drug containers for infusion or syringe pumps using the same standard fill-and-finish process. These medicament containers can be aseptically filled in a cost-effective manner as is common industry practice.

It should be understood that the above description provides examples of the disclosed systems and techniques. However, it is contemplated that other implementations of the present disclosure may differ in detail from the above examples. All references to the disclosure or examples thereof are intended to reference the particular example being discussed at this point and are not intended to more fully imply any limitation as to the scope of the disclosure. All language of praise and dispute regarding certain features is intended to indicate a lack of preference for those features, but does not exclude such features from the scope of the disclosure entirely unless otherwise indicated.

The use of the terms "a" and "an" and "the" and "at least one" and similar referents in the context of describing the invention are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The use of the term "at least one" followed by one or more items (e.g., at least one of "a and B") should be construed to mean one item selected from the listed items (a or B) or any combination of two or more of the listed items (a and B) unless otherwise indicated herein or clearly contradicted by context.

Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context.

Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the disclosure unless otherwise indicated herein or otherwise clearly contradicted by context.