GB2624630A

GB2624630A - Actuation system for an auto injector

Info

Publication number: GB2624630A
Application number: GB2217434.6A
Authority: GB
Inventors: York Thomas
Original assignee: Richmond Pharmacology Ltd
Current assignee: Richmond Pharmacology Ltd
Priority date: 2022-11-22
Filing date: 2022-11-22
Publication date: 2024-05-29
Also published as: WO2024110745A1; GB202217434D0

Abstract

The system comprises an actuator 410 configured for operating a syringe of an auto injector, the actuator having a first operating time that starts upon activation of the system. The system further comprises a timer 420 having a second operating time that starts upon activation of the system and activation means 430 configured to activate the system. The actuator and the timer start simultaneously upon activation of the system and the first operating time is independent of the second operating time. The actuator may be a spring or screw-thread drive train and the timer may be a mechanical timer configured to adjust and set the second operating time.

Description

ACTUATION SYSTEM FOR AN AUTO INJECTOR

FIELD OF THE INVENTION

The present invention relates to auto injectors. In particular, the present invention relates to an actuation system for an auto injector, for example for use in medical trials. The actuation system may be formed integrally with the auto injector or provided as a separate element that can be retrofitted to an auto injector.

BACKGROUND

In medical trials, such as placebo-controlled trials, it is important that the study is a blind trail, so as not to bias the findings. A blind trial means that the members involved in the trial (e.g., trial volunteers receiving injections, and/or members of staff, such as investigators/administrators) do not know if the recipient is receiving the trial medicine or a placebo. Where the trial medicine is given as an injection, it is important that the recipients and administrators are not able to differentiate between an active injectate (i.e., the trial medicine) and a placebo injectate.

However, in such trials, because an active injectate and a placebo injectate will have different viscosities (due to their differing compositions), the haptic feedback and the time taken to inject the active injectate compared to the placebo injectate may vary. When using a conventional syringe, the haptic feedback from the syringe plunger varies with viscosity (the more viscose the injectate, the stronger the haptic feedback), meaning the administrator may be able to feel the difference between injecting the activate injectate and the placebo injectate. This could lead to unblinding, which is problematic in trials. For example, it can create concerns about the impartiality of the data collected and/or the validity of the results. The administrator(s) in question must then be taken off any other work concerning the trial, or be deliberately unblinded. This increases staffing costs as a blinded counterpart is then also required.

To account for haptic feedback when using a conventional syringe, an auto injector can be used. An auto injector is a medical device that automatically delivers a dosage of injectate, such as a drug, upon activation by a user. Auto injectors can be self-administrated by patients or administrated by another. For example, by a parent, a carer or an administrator in a medical trial.

When using an auto injector, the injectate is physically delivered by a syringe actuator mechanism, such as a spring, rather than by manual pressure from the administrator. The administrator need only activate the auto injector by pressing a button/switch to release the spring. As such, the administrator receives no direct hapfic feedback from the auto injector.

However, because of the varying viscosities, and because the force applied to the syringe by the auto injector during operation is standardised to the specific auto injector (determined by the mechanical properties of the syringe actuator), the time taken to deliver the injection is variable -a viscid injectate will take discernibly longer to deliver than an inviscid one. This is because the actuator exerts an equal pressure on the syringe for each use (determined by the mechanical properties of the syringe actuator) regardless of the viscosity. Therefore, using a known auto injector in medical trials can result in unblinding, due to the potentially noticeably different lengths of time to deliver an injection.

In addition, known auto injectors often generate an alarm (e.g., an audible or visual signal) on completion of an injection. However, this also leads to unblinding because the alarm may further highlight the differences in injection times between injectates of varying viscosities, i.e., the alarm may sound earlier for an injection containing the least viscous injectate versus the more viscous injectate. However, without a completion alarm, the syringe may be removed too quickly, which can lead to issues due to insufficient dwell time of the syringe. The administrator could run the trial unblinded, such that this is not an issue, but this is significantly more costly and inconvenient, because additional staff will be required. An alternative solution is to try matching the viscosities of the trial and placebo injectates by using additives, to attempt to make the injection times the same. However, this can lead to problems with the placebo no longer being a true placebo (due to the additives).

An example of a known auto injector is the Owen Mumford Autoject 2. This auto injector includes a spring for actuating the syringe and audible and visual indicators that signal the start and end of an injection. It does not include a timing mechanism.

Another example of a known auto injector is the Springboard Pro Gentle-Ject. This device allows a user to set the injection time depending on their preference for a shorter or longer (and gentler) injection. The device includes a compression spring for actuating the syringe. The injection time is directly controlled by how compressed this spring is. For example, a user wanting a gentler injection would set the injection delivery time to the upper limit, such that the spring depresses the plunger over a longer period and delivers the injectate at a reduced rate.

A further known auto injector is the Phillips-Medisize Smart Autoinjector. This auto injector uses a microprocessor controlled drive train to vary the force required to achieve a user's desired target injection time. The device is adaptable to work with both low and high viscosity injectates by adjusting the applied force to maintain the target injection time.

These known auto injectors are not set up to control for trial blindness because their completion alarms are dictated by the injection delivery time. As such, an administrator would be able to distinguish between injectates of varying viscosity.

There is therefore a need to standardise medical trial injection times such that those involved in the trial, e.g., an administrator, cannot distinguish between an active injectate and placebo with varying viscosities, thereby maintaining trial blinding.

SUMMARY

In a first aspect, there is an actuation system for an auto injector. The system comprises an actuator configured for operating a syringe of an auto injector. The actuator has a first operating time that starts upon activation of the actuation system. The actuation system further comprises a timer having a second operating time that starts upon activation of the actuation system. The actuation system further comprises activation means configured to activate the actuation system. The actuator and the timer are activated by the activation means to start simultaneously upon activation of the actuation system. The first operating time is independent of the second operating time. Advantageously, the actuator and timer are activated simultaneously, but run independently of each other. As such, the second operating time may be controlled as desired completely independent of the first operating time. The independent timing controls enable a medical trial to remain blinded because the second operating time may be set such that it is not possible for those involved in the medical trial to distinguish between different types of injectates being investigated. 4 -

The timer may be configured to generate an alarm at the end of the second operating time. The alarm signals the end of the second operating time, i.e., an alarm signal is provided to signify the time at which an auto injector should be removed from the recipient during a blind medical trial.

The second operating time may be adjustable and/or preset. An adjustable second operating time allows the actuation system to be used with a variety of auto injectors and syringes, as the second operating can be adjusted as required to maintain blinding. Presetting the second operating time ensures that those involved in the blind medical trial cannot distinguish between varying injectates, as the second operating time is fixed before use.

The second operating time may be equal to or greater than the first operating time. Setting the second operating time to be at least the same length as the first operating time means that the alarm with be generated after exactly the same length of time for every injection, regardless of which injectate is being injected during the blind trial. This stops those involved in the trial from being able to distinguish between varying injectates because it is not possible to know when the injection has been completed.

The first operating time may be the injection delivery time required for a dosage of an injectate to be fully administered to a recipient using the auto injector. Optionally, the first operating time may include the syringe's dwell time. Furthermore, the injectate may be one of a plurality of injectates. In this case, the first operating time is the injection delivery time required for a dosage of the most viscous injectate of the plurality of injectates to be fully administered to the recipient using the auto injector.

The actuator may comprise a spring or a screw-thread drive train.

The timer may be a mechanical timer configured to adjust and set the second operating time. Optionally, the mechanical timer comprises a timer spring, a gear, an escapement, a dial and an alarm. Also, the mechanical timer may further comprise a cap operatively coupled to the timer spring. The cap may include the dial, and the dial is twistable to adjust and set the second operating time.

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Alternatively, the timer may be a digital timer configured to adjust and set the second operating time.

The activation means may comprise a switch or a push-button.

The activation means may be communicatively coupled to the actuator and to the timer. Communicatively coupling the activation means to the actuator and timer allows simultaneously activation of the actuator and timer without necessarily requiring the activation means to be physically coupled to the actuator and timer auto injector. In one example, the activation means may be physically coupled to the actuator and to the timer.

Alternatively, the activation means may be physically remote from the actuator and/or the timer. For example, the activation means could be part of a centrally controlled activation means that sends a signal to an auto injector to trigger the activation.

In a second aspect, there is an auto injector comprising a housing, a syringe positioned within the housing, and the actuation system as described above. The actuator is configured to apply a force to the syringe to operate the syringe upon activation of the actuation system.

The actuation system may be formed integrally with the auto injector. Alternatively, the actuation system may be releasably coupled to the housing of the auto injector.

The actuation system may be operably coupled to the syringe.

The auto injector may be configured to retract the syringe on or after the end of the second operating time. Optionally, the auto injector may be configured to retract the syringe automatically or manually. Retracting the syringe after use is a safety feature that helps prevent 'needle-stick' injuries to users.

The timer may be configured to generate the alarm at the end of the second operating time.

In a third aspect, there is a blind trial system comprising a plurality of auto injectors. Each auto injector of the plurality of auto injectors is an auto injector as described above.

The syringe of each auto injector contains an injectate of a plurality of injectates that have 6 -varying viscosities. The second operating time of each auto injector is preset to be the same. The second operating time is equal to or greater than the injection delivery time required for the most viscous injectate of the plurality of injectates to be fully administered to a recipient using the auto injector.

BRIEF DESCRIPTION OF THE DRAWINGS

In order that the invention can be more readily understood, reference will now be made, by way of example only, to the accompanying drawings in which: Figure 1 is a block diagram of an actuation system for an auto injector.

Figure 2 is a cross sectional view of an exemplary auto injector.

Figure 3 is an external view of an exemplary auto injector comprising a mechanical timer and a spring actuator.

Figure 4A is a cross sectional view of the auto injector of figure 3, wherein the syringe is in a retracted/pre-deployed position.

Figure 4B is a cross sectional view of the auto injector of figure 3, wherein the syringe is in a deployed position.

Figure 5 is a flow diagram of a method for loading a prefilled syringe into an auto injector.

Figure 6 is a flow diagram of a method for unloading a used syringe from an auto injector.

Figure 7 is a flow diagram of a method of injecting a recipient using an exemplary auto injector.

DETAILED DESCRIPTION OF THE INVENTION

In medical trials, it is often important that the trial remains blinded by stopping those involved being able to differentiate between the administration of different injectates (e.g., the drug being trialled compared to a placebo) so as not to bias the findings. However, because the injectates may have different viscosities, which is due to their differing compositions, their injection delivery times will vary. Accordingly, participants and/or administrators/investigators in a medical trial will be able to tell the difference between the injections, leading to unblinding. The present invention addresses this problem as described below. 7 -

An exemplary actuation system 100, as shown in the block diagram of figure 1, is provided for use in an auto injector, such as the exemplary auto injectors 250, 350 shown in figures 2, 3, 4A and 4B. The actuation system 100 comprises a dual actuation mechanism that masks the difference in injection delivery times between injectates of varying viscosities, such that a medical trial remains blinded. The actuation system 100 comprises an actuator 110 configured for operating a syringe of an auto injector. The actuator 110 has a first operating time that starts upon activation of the actuation system 100. The actuation system 100 also comprises a timer 120 having a second operating time that starts upon activation of the actuation system 100. The actuation system 100 further comprises activation means 130 configured to activate the actuation system 100. The actuator 110 and the timer 120 are activated by the activation means 130 to start simultaneously upon activation of the actuation system 100. The first operating time is independent of the second operating time.

The first operating time of the actuator is the injection delivery time, i.e., the first operating time is the injection delivery time required for a dosage of an injectate to be fully administered to a recipient using the auto injector. A viscid injectate will have a longer injection delivery time compared to an inviscid injectate. The injection delivery time may also include a syringe's dwell time. The dwell time is the additional time after the plunger of a syringe has stopped moving but the delivery of the injectate has not yet fully completed.

For many conventional auto injectors, a user is required to keep holding the auto injector against their skin for a predetermined amount of time after the plunger has stopped moving so as to ensure that the injectate is fully delivered and the needle is not removed too soon. Some known auto injectors include the dwell time in their 'injection completed' alarm so as to avoid this manual dwell time step. The terms first operating time and injection delivery time can be used interchangeably.

The second operating time of the timer is the auto injector withdrawal time, i.e., the second operation time is the time at which a user is notified to remove the auto injector from a recipient's skin. The timer generates an alarm at the end of the second operating time, this alarm alerts the user that it is time to remove the auto injector from contact with the recipient's skin. The second operating time is adjustable and can be preset by the user. The terms second operating time and auto injector withdrawal time can be used interchangeably. 8 -

In conventional auto injectors that include a timer, the conventional timer generates an alarm at the end of the injection delivery time (i.e., on completion of delivery of the injection, with or without the dwell time included). In contrast, the actuation system 100 of the present invention is configured such that the timer 120 of the actuation system 100 generates an alarm at the end of the auto injector withdrawal time, which is independent of the injection delivery time (with or without the dwell time included). Although the auto injector withdrawal time and the injection delivery time are independent of each other, they are both triggered to start simultaneously by the activation means 130 of the actuation system 100. As such, a user has the ability to control the length of the auto injector withdrawal time and the alarm as desired (independent of the injection delivery time for the injectate being injected). Therefore, the auto injector can be used in a medical trial without revealing the injection delivery time for an injectate.

More specifically, the auto injector withdrawal time is adjustable and can be preset by a user to be a time greater than or equal to the injection delivery time for an injectate in question. In one example, the auto injector withdrawal time may be preset before delivery to the user, such that the auto injector is provided (e.g., the auto injector is provided to an administrator carrying out the injections in a medical trial) with the auto injector withdrawal time already set, meaning that the timer 120 cannot be changed by the user (e.g., the administrator). In an alternative example, the timer 120 can be set by the user (e.g., the administrator). In scenarios where a plurality of injectates are being used, for example in medical trials where different injectates are being tested, the auto injector withdrawal time is set at a time equal to or greater than the injection delivery time for the most viscous injectate of the plurality of injectates. By setting the auto injector withdrawal time to be at least the same length as the time required to fully administer the most viscose injectate to a recipient, any feedback to the administrator (e.g., an audible/visual/haptic alert from the alarm) will be after exactly the same length of time for every injection, regardless of which injectate is being injected. As such, those involved in the trial are not able to distinguish between the plurality of injectates, and so the trial remains blinded.

In figure 2, an exemplary auto injector 250 is illustrated. The auto injector 250 comprises a housing 260. A syringe 270 (shown in dashed lines) is positioned within the housing 260. The syringe 270 comprises a plunger 272, a barrel 274 and a needle 277.

The exemplary auto injector 250 shown in figure 2 may be used with the exemplary actuation system 100 shown in figure 1. As shown in figure 2, the actuation system 100 is positioned within the housing 260 and is operably coupled to an end 273 of the plunger 272. In some examples, the actuation system 100 is formed integrally with the auto injector 250. However, in other examples, the actuation system 100 is instead provided separately to the auto injector 250. For example, the actuation system 100 may be releasably coupled to the auto injector 250 housing such that the actuation system 100 can be retrofitted to conventional auto injector devices.

In figure 3, an exemplary auto injector 350 is illustrated. Figures 4A and 4B provide cross sectional views of the exemplary auto injector 350 shown in figure 3. In figure 4A, a syringe 470 is shown in a retracted/pre-deployed position (i.e., the position before and after use of the auto injector 350, when the auto injector 350 is not in use), In figure 4B, the syringe 470 is shown in a deployed position (i.e., the position during use of the auto injector 350 to inject a recipient). The exemplary auto injector 350 of figures 3, 4A and 43 may be configured as the auto injector 250 shown in figure 2, or may have an alternative set up. In the depicted set up, the auto injector 350 comprises a housing 360 for accommodating components of the auto injector. The housing 360 may be configured as the housing 260 shown in figure 2, or may have an alternative set up. As shown in figures 2, 3, 4A and 4B, the housing 260, 360 has a hollow cylindrical shape, but may be any other suitable shape.

The housing 260, 360 may be made of a plastic material, such as Acrylonitrile butadiene styrene (ABS) or Polyvinyl chloride (PVC), or another suitable plastic material. Other suitable housing materials, such as but not limited to ceramics, stainless steel and aluminium, may be used instead. As shown in figure 3, the housing 360 includes an upper portion 361 and a lower portion 366. Positioned between the upper portion 361 and the lower portion 366 of the housing 360 is an optional inner housing component 364 which holds and stabilises the syringe 470 within the housing 360. As such, the housing 360 shown in figure 3 has a three-part formation. However, the housing 260, 360 may alternatively have a one-part or two-part formation that does not include the inner housing component. For example, the housing 260, 360 may comprise one integral housing portion.

Alternatively, the housing 260, 360 may comprise the upper portion 361 and lower portion 366 in direct contact with each other and releasably or permanently coupled together. In these cases, the syringe 270, 470 is stabilised by the housing portion(s).

-10 -In the configuration shown in figures 3, 4A and 4B, the upper portion 361 of the housing 360 has a first end 362 and a second end 363. The first end 362 of the upper portion 361 is configured to be releasably coupled to a first end 364a of the inner housing component 364. In one example, the first end 362 of the upper portion 361 forms a snap lock fastening with the first end 364a of the inner housing component 364. However, any other suitable form of releasable fastening may be used, for example a screw threaded or friction fit fastening. In alternative examples, the first end 362 of the upper portion 361 may be permanently fixed or integral with the first end 364a of the inner housing component 364.

In the configuration shown in figures 3, 4A and 4B, the lower portion 366 of the housing has a first end 367 and a second end 368. The first end 367 of the lower portion 366 may be removably coupled, such as by a snap lock, screw threaded or friction fit fastening, to a second end 364b of the inner housing component 364. In alternative examples, the first end 367 of the lower portion 366 may be permanently fixed or integral with the second end 364b of the inner housing component 364. As shown in figure 3, the second end 368 of the lower portion 366 has a frustoconical shaped upper part 368a and a cylindrical lower part 368b. The second end 368 may however have any other suitable shape (e.g., domed). The lower part 368b of the second end 368 defines a skin engaging surface 369a comprising an opening 369b through which a needle 477 of the syringe 470 can be deployed and retracted during operation of the auto injector 350. The skin engaging surface 369a is configured to maintain contact with the recipient's skin during the injection.

The second end 368 of the lower portion 366 acts a needle guard to protect the needle 470 when not in use, as shown in figures 3 and 4A. For example, before use, the second end 368 of the lower portion 366 covers the needle 477 when the syringe 470 is in a retracted/pre-deployed position. After use (i.e., when the auto injector 350 has been removed away from the recipient's skin), the used syringe 470 is retracted back through the opening 369b (i.e. the syringe 470 is returned from a deployed to retracted/pre-deployed position), such that the second end 368 of the lower portion 366 again covers the needle 477. The auto injector 350 may be configured to retract the syringe 470 manually or automatically at a suitable time, for example after an alarm 425 has signalled the end of the auto injector withdrawal time. In other words, the syringe 470 may be retracted after the injection has been delivered, the alarm 425 has signalled the end of the auto injector withdrawal time, and the auto injector 350 has then been removed from the recipient's skin surface. In another example, the syringe 470 may be retracted before the end of the auto injector withdrawal time, e.g., after the injection delivery time but before the auto injector withdrawal time (where the auto injector withdrawal time has been set to a time greater than the injection delivery time). The manual or automatic retraction is a useful safety feature that helps prevent 'needle-stick' injuries to users. In one example, the syringe 470 is manually retracted via a slider positioned on a track (not shown) in the housing 360 and the slider is operably coupled to the syringe 470. In this example, after the injection has been fully delivered to the recipient, the syringe 470 may be retracted by a user moving the slider along the track in a direction away from the opening 369b in the lower portion 366 of the housing 360. The movement of the slider moves the syringe 470 back upward within the housing 360 to its retracted/pre-deployed position (e.g., the retracted/pre-deployed position is the position of a syringe 470 retracted within an auto injector, as shown in figure 4A. The slider and tracker are not shown in figure 4A). In another example, the syringe 470 is automatically retracted via use of a retraction spring 440 (shown in figures 4A and 4B) mounted within the lower portion 366 of the housing 360. A first end 442 of the retraction spring 440 is positioned above the opening 369b in the housing 360 and sits on an inner surface of the upper part 368a of the second end 368 of the lower portion 366 of the housing 360. The retraction spring 440 extends upward from the first end 442 within the housing 360 to a second end 444 that is positioned in line with a first end 474a of a barrel 474 of the syringe 470. The syringe 470 sits within the coils of the retraction spring 440 (i.e., the retraction spring 440 extends around the syringe barrel 474). The retraction spring 440 may be any type of spring suitable for retracting the syringe 470 after the injection has been completed, such as a helical spring (e.g., a helical compression spring). In this example, activation of the actuator 410 to apply a force on a plunger 472 of the syringe 470 simultaneously compresses the retraction spring 440 as the syringe 470 is moved downward to its deployed position (figure 4B). During operation of the syringe 470 to inject the recipient, the retraction spring 440 remains compressed. A lip (not shown) on an inner surface of the housing 360 (e.g., a lip on an inner surface of the inner housing component 364) holds the compressed retraction spring 440 in place until retraction of the syringe 470 is required. After the injection has been fully delivered to the recipient, the retraction spring 440 is automatically released from its compressed state, pulling the syringe 470 back up within the housing 360 to its retracted/pre-deployed position (figure 4A) as the retraction spring 470 decompresses, thereby sheathing the needle 477 inside the second end 368 of the lower portion 366.

-12 -Once the syringe 470 is in the retracted position (whether via manual or automatic retraction), the activation means 430 may be re-engaged with the actuator 410 so as to hold the syringe 470 in its retracted position. For example, the activation means 430 may be directly reengaged with the actuator 410. Alternatively, the activation means 430 may engage with an additional mechanism (not shown) configured to retain the syringe 470 after use. In all cases, the auto injector 350 must not be able reactivate itself after the syringe 470 has been retracted to its retracted/pre-deployed position. If the auto injector 350 is reusable, the auto injector 350 may be activated again later, once the used syringe 470 has disposed of and a fresh syringe has been loaded into the auto injector housing 360.

The exemplary auto injector 350 may also include a movable cap (not shown) that can be placed over the lower part 368b of the second end 368 of the lower portion 366 to cover the opening 369b in the skin engaging surface 369a and shield the needle 477 when not in use.

The syringe 470 may be any known syringe that is compatible for use with an auto injector. For example, the syringe 470 may be fixed needle or Luer fit type syringes with ranges (not limited to) 0.3m1 through to 2m1. As shown in the example of figures 4A and 4B, the syringe 470 comprises the barrel 474 with the first end 474a and a second end 474b.

The needle 477 is coupled to the first end 474a of the barrel 474. A first end 472a of the plunger 472 is movably received at the second end 474b of the barrel 474. The barrel 474 is configured to hold an injectate and the plunger 472 is moveable with respect to the barrel 474 such that the syringe 470 can be adjusted to hold different volumes of injectate within the barrel 474. During operation of the syringe 470, the plunger 472 is configured to be resiliently driven toward the first end 474a of the barrel 474 such that injectate flows out of an opening in the first end 474a of the barrel 474, through the needle 477 and, when in position, into a recipient's body.

In the configuration shown in figures 3, 4A and 4B, the inner housing component 364 (or housing portion(s) 361, 366 if no inner housing component is present in the auto injector 350) supports the syringe 470 in a fixed position within the housing 360 when the auto injector 350 is not in use. This stabilisation is provided by preventing movement in any plane other than downwards through the direction of the plunger 472. For example, the -13 -barrel 474 of the syringe 470 and the inner housing component 364 may have a close fit that prevents any unwanted movement, or may otherwise be held in position.

In the configuration shown in figures 3, 4A and 4B, the auto injector 350 further comprises an actuation system 400, one example being the same actuation system 100 as shown in figure 1. The actuation system comprises an actuator 410 for operating the syringe 470, a timer 420, and activation means 430 for simultaneously activating the actuator 410 and the timer 420.

As shown in the example of figures 4A and 4B, the actuator 410 comprises a spring 480 for operating the syringe 470. The spring 480 may be any type of spring suitable for operating a syringe in an auto injector, such as a helical spring (e.g., a helical compression spring) or a conical spring (e.g., a conical compression spring). The spring 480 has a first end 481 and a second end 482. Once the syringe 470 has been loaded into the auto injector housing 360, the first end 481 of the spring 480 is operatively coupled to a second end 472b of the plunger 472. For example, the first end 481 of the spring 480 is configured to contact the surface of the second end 472b of the plunger 472 such that the spring 480 and plunger 472 maintain direct contact during operation of the auto injector 350. In other examples, the first end 481 of the spring and the second end 472b of the plunger 472 need not be in direct contact, but may be coupled via an internal coupling component (not shown). The second end 482 of the spring 480 is configured to contact an interior surface 490 of the upper portion 361 of the housing 360. The interior surface 490 provides a fixed surface for the spring 480 to act against. The interior surface 490 remains static relative to the moving plunger 472 during operation of the auto injector 350.

Therefore, during operation, the first end 481 of the compressed spring 480 expands away from the fixed interior surface 490 and resiliently drives the plunger 472 toward the first end 474a of the barrel 474, such that the injectate is pushed through the opening in the first end 474a of the barrel 474, through the needle 477 and into the recipient's body.

As also shown in the example of figures 3, 4A and 4B, the timer 420 comprises a mechanical timer. The mechanical timer may be any conventional mechanical timer. In the example shown, the mechanical timer includes a timer spring 421, a gear 422, an escapement 423, a dial 424 and the alarm 425. The timer spring 421 may be a spiral spring, a clockspring, a mainspring or any other suitable type of timer spring for use in a mechanical timer. The gear 422 may be any suitable type of gear for use in a mechanical -14 -timer, such as a spur gear. The alarm 425 generates a signal to indicate the end of the auto injector withdrawal time. This signal may be audible, visual, haptic, or combination thereof. In the example shown in figures 4A and 43, the alarm 425 includes a striking mechanism configured to generate an audible signal when triggered by completion of the timer. The striking mechanism comprises a hammer 426 with a plate and bell 427. In other examples, an audible alarm may instead be a buzzer, a digital/electronic alarm or any other suitable alarm that provides audible feedback. A visual alarm may be electrical, digital or any other suitable alarm that provides visual feedback. A haptic alarm may include vibrations or any other suitable type of alarm that provides haptic feedback. The timer spring 421, gear 422, escapement 423 and dial 424 are operatively coupled such that turning the dial 424 sets the auto injector withdrawal time.

The mechanical timer also comprises an optional cap 428, as shown in figure 3, but not in figures 4A and 4B. The cap 428 covers the internal mechanisms of the timer 420 and, as shown in figures, may include the dial 424 that is used to adjust and set the auto injector withdrawal time. Before use, the auto injector withdrawal time is set by twisting the dial 424 to any suitable desired amount, such as 5 seconds, 10 seconds, 15 seconds and so on. Twisting the dial 424 compresses the timer spring 421, storing energy in the timer spring 421. Upon activation, the compressed timer spring 421 begins to unwind, turning the gear 422 via the escapement 423. The escapement 423 works as a catch and release rocking mechanism that keeps the mechanical timer in sync with the progression of time. With each unit of time that passes by, the escapement 423 stops a tooth of the gear 422 and then releases it, allowing the gear 422 to rotate, tooth by tooth. The rotation of the gear 422 moves the dial 424 back toward its starting position at a constant rate. Once the timer spring 421 has unwound and the dial 424 has returned to its starting position, the alarm 425 is generated. For example, the alarm 425 may provide an audible signal when the hammer 426 strikes the bell and plate 427.

In the configuration shown in figures 3, 4A and 43, the actuation system 400 further comprises activation means 430 configured to activate the actuator 410 and the timer 420 to start simultaneously. The activation means 430 may comprise a switch or button configured to trigger the activation upon user input. For example, the switch may be a mechanical switch, such as a rocker switch or a toggle switch, or the switch may be an electronic switch. The button may be a mechanical or electrical push button. In the example as shown in figures 4A and 4B, the activation means comprise a rocker switch 431 -15 -positioned in the upper portion 361 of the housing 360. The rocker switch 431 is provided through the upper portion 361 of the housing 360 such that a first portion 431a of the rocker switch 431 extends outwardly from an external surface of the upper portion 361 of the housing 360 and a second portion 431b of the rocker switch 431 extends inwardly from an internal surface of the upper portion 361 of the housing 360. The rocker switch 431 comprises a first leg 432 that extends between the second portion 431b of the rocker switch 431 and the gear 422 of the timer 420. The rocker switch 431 also comprises a second leg 434 that extends between the second portion 431b of the rocker switch 431 and the spring 480. As shown in figure 4A, when not in use, the syringe 470 is in a retracted position within the housing 360 (i.e., such that the needle 477 does not extend through the opening 369b in the lower portion 366 of the housing 360), and a distal end 433 of the first leg 432 is engaged with a tooth of the gear 422 such that the gear 422 cannot rotate. Similarly, a distal end 435 of the second leg 434 is engaged with one of the coils of the spring 480 such that the spring 480 is held in a compressed configuration, and the syringe 470 is in the retracted/pre-deployed position. The rocker switch 431 is configured to activate the both the spring 480 and the timer 420 at the same time. Upon activation, for example when a user presses the rocker switch 431, the first leg 432 and the second leg 434 of the rocker switch 431 are simultaneously released from their engaged positions (shown in figure 4A) to their released positions (shown in figure 4B). In their released positions, the distal ends 433, 435 of the rocker switch legs 432, 434 are moved away from the gear 422 and spring 480 simultaneously such that they are no longer engaged with the gear 422 or spring 480. The timer 420 then begins counting down the auto injector withdrawal time and the spring 480 begins expanding downwards, applying a force to the syringe 470 to move it downwards into its deployed position (i.e., such that the needle 477 extends through the opening 369b in the lower portion 366 of the housing 360) and into the recipient's skin. The applied force from the spring 480 then drives the syringe plunger 474 further into the barrel 474 to inject a recipient with the injectate contained within the barrel 474 of the syringe 470.

The auto injector 250, 350 of any example described herein may be provided as a single use, disposable device with a syringe 270, 470 that is already located within the housing 260, 360. Alternatively, the auto injector housing 260, 360 and syringe 270, 470 may be provided separately such that the auto injector housing 260, 360 can be reused multiple times with fresh syringes. One example of such an auto injector 350 is as described above (and shown in figures 3, 4A and 4B). In this case, the auto injector -16 -housing 360 may be loaded with a prefilled syringe using method 500, as shown in figure 5. At step 510 of method 500, the upper portion 361 of the housing 360 (shown in figures 3, 4A and 4B) is disconnected from the inner housing component 364 (or lower portion 366, if no inner housing component 364 is present), for example the user can disconnect the housing portions 361, 364, 366, or the housing portions 361, 364, 366 can be provided separately, i.e. in an already disconnected state. At step 520, a prefilled syringe 470 is positioned, needle 477 first, within the lower portion 366 of the housing 360, such that the needle 477 aligns with the second end 368 of the lower portion 366 of the housing 360 and the syringe 470 is stabilised by the inner housing component 364 (or the lower portion 366 of the housing 360). At step 530, the upper housing 361 is connected/reconnected to the inner housing component 364 (or the lower portion 366 of the housing 360) using a suitable fastening mechanism, such as a snap lock or threaded engagement, thereby enclosing the syringe 470 within the housing 360 in a retracted/pre-deployed position, ready for use. As part of step 530, the actuator 410 is brought into (direct or indirect) contact with the second end 472b of the plunger 472 such that upon activation of the activation means 430, the actuator 410 can drive the syringe 470 downwards into its deployed position.

If it is desired to unload a used syringe from the auto injector 250, 350 after use (for example where the auto injector is designed to be a multiple use auto injector), a user may follow method 600, as shown in figure 6. At step 610 of method 600, the upper portion 361 of the housing 360 is disconnected from the inner housing component 364 (or lower portion 366, if no inner housing component 364 is present). At step 620, the used syringe 470 is removed from the lower portion 366 of the housing 360 and disposed of. Optionally, at step 630, a fresh syringe 470 may be positioned within the auto injector housing 260, 360 according to method 500. At step 640, the upper housing 361 is reconnected to the inner housing component 364 (or lower portion 366) using the snap lock or other suitable fastening, either with or without the fresh syringe 470 positioned within the auto injector housing 360.

A recipient may be injected using an auto injector 250, 350 as per method 700, as shown in figure 7. For example, using the exemplary auto injector 350 illustrated in figures 3, 4A and 4B, or any auto injector as described herein. In step 710 of method 700, the auto injector withdrawal time is set to be equal to or greater than the injection delivery time (which may include the syringe's dwell time) of an injectate to be injected. The auto injector withdrawal time is set depending on the viscosity of the injectate being injected, for -17 -example by turning the dial 424 of the mechanical timer to the desired time. This step may be performed by a user, e.g., the recipient or an administrator in a medical trial. In an alternative example, this step could be carried out before delivery to the user, for example, the auto injector withdrawal time could be preset by a member of a medical trial team, during manufacture or be factory set. Accordingly, in this alternative example, a user cannot change the timer 420 because the auto injector withdrawal time has been preset. At step 720, the auto injector 350 is loaded with a prefilled syringe 470 according to method 500. If the auto injector is a single use, disposable device, then step 720 is not required. The order of steps 710 and 720 is interchangeable. At optional step 730, if a cap is provided on the auto injector 350, the cap is moved off of the lower part 368b of the second end 368 of the lower portion 366 of the housing 360 to reveal the opening 369b through which the needle 477 is to be deployed during operation. Next, at step 740, the auto injector 350 is positioned such that the opening 369b of the skin engaging surface 369a is placed in direct contact with the recipient's skin, for example on the recipient's arm, thigh or any other suitable location on the recipient's body. Ideally, the auto injector 350 should be positioned approximately perpendicular to the skin surface so as to ensure a clean insertion and withdrawal of the needle 477 and to avoid causing any unnecessary pain or damage to the recipient. At step 750, the actuation system 400 is activated using the activation means 430, for example by pressing the rocker switch 431. In the example using the rocker switch 431, the rocker switch 431 may be pressed by the recipient or another user, such as an administrator in a medical trial. Upon activation, the actuator 410 (e.g., spring 480 as shown in figures 4A and 4B) and the timer 420 (e.g., mechanical timer as shown in figures 4A and 4B) are simultaneously activated. This triggers the start of the injection delivery time and the start of the auto injector withdrawal time. The spring 480 is activated by release of the second leg 434 of the rocker switch 431 from engagement with the spring 480. Simultaneously, the timer 420 is activated by released of the first leg 432 of the rocker switch 431 from engagement with the gear 422. At step 760, the compressed spring 480 expands from its compressed state, exerting a force onto the second end 472b of the plunger 472 as the spring 480 returns toward its non-compressed state. This force pushes the syringe 470 into a deployed position, i.e., the spring 480 pushes the syringe 470 toward, and the needle 477 into, the recipient's skin. Once the needle 477 has been inserted into the recipient's skin, the force from the spring 480 then pushes the plunger 472 toward the first end 474a of the barrel 474, thereby moving the injectate through the opening in the first end 474a of the barrel 474, through the needle 477 and into the recipient's subcutaneous tissue. The force against the plunger 472 is opposed by the -18 -housing 360 at the point when the syringe 470 has been moved to its deployed position, thereby stopping the syringe barrel 474 from moving further downward so that only the plunger 472 continues to move under the force and deliver the injectate. At the same time, the compressed timer spring 421 unwinds as the timer 420 counts down and the dial 424 returns to its starting position. At step 770, the injection delivery time is reached when the injectate has been fully delivered to the recipient. The injection delivery time may include any dwell time associated with the syringe 470. The auto injector 350 does not provide any signal to indicate the end of the injection delivery time (thereby keeping the injection delivery time hidden from an administrator during a medical trial). At step 780, when the dial 424 has returned to its starting position, the alarm 425 signals the end of the auto injector withdrawal time. For example, via an audible, visual and/or haptic indicator. This signals to the user (e.g., administrator or recipient) that the injection has been fully completed and the auto injector 350 may be removed from the recipient. If at step 710, the auto injector withdrawal time is set as equal to the injection delivery time, then step 780 will occur at the same time as step 770. If at step 710, the auto injector time is set as greater than the injection delivery time, then step 780 will occur after step 770. At step 790, after the alarm 425 has signalled the end of the auto injector withdrawal time, the syringe 470 may be retracted (manually or automatically) back upward within the housing 360 for safety. As such, when the auto injector 350 is used in a blind medical trial with injectates of varying viscosities, as described in further detail below, those involved in the trial, such as the participants and/or administrators, are unable to distinguish between the injectates. When step 790 is carried out in a blind medical trial, the syringe 470 must not be retracted before the end of the auto injector withdrawal time as this could be unblinding. For example, if the syringe 470 is retracted before the alarm 425 signals the end of the auto injector withdrawal time, then the recipient and/or administrator may well be able to distinguish between the different injectates (because they have different injection delivery times). Accordingly, in a blind trial, the syringe's retraction time must be set at or after the end of the auto injector withdrawal time.

The auto injector, for example the exemplary auto injectors 250, 350 as shown in any of figures 2, 3, 4A and 4B or any auto injector as described herein, may be used in a blinded medical trial according to method 700 described above. In the simplest example, the medical trial comprises a viscid active injectate and an inviscid placebo injectate. However, the auto injector 250, 350 may also be used in more complex medical trials, such as where several injectates of varying viscosities are being trialled.

-19 -Before starting the trial, at step 705, which precedes step 710 of method 700, the active injectate(s) and the placebo injectate(s) are both tested to calculate their respective injection delivery times, including any syringe dwell time. For example, the injection delivery times are assessed by an unblinded member of staff, in other words, those who are not part of the blind trial. For example, the assessment may be carried out in a laboratory or pharmacy. The assessment may include a method, such as human tissue analogue, where the delivery time of each injectate is recorded. Each injectate is tested by timing the length of time required for the injectate to be fully delivered (which may include any dwell time). In one example, the injection delivery time for the activate injectate is 15 seconds and the injection delivery time for the placebo injectate is 5 seconds. These times are merely given as an example in this scenario. Any suitable injection delivery time and auto injector withdrawal time are possible. The injection delivery time for each injectate may be any suitable time that is dependent upon the injectate viscosity, and the syringe/actuator combination of the auto injector used. After step 705, the method then proceeds to step 710, i.e., the auto injector withdrawal time is set to be equal to or greater than the injection delivery time of the injectate. In scenarios where there is more than one injectate, the auto injector withdrawal time is set to be equal to or greater than the injection delivery time of the most viscous injectate. In the specifically described example, the active injectate is the most viscous injectate and it has an injection delivery time of 15 seconds (which may include any dwell time). As such, in step 710, the auto injector withdrawal time is set to be 15 seconds or more. For example, the auto injector withdrawal time may be set at 18 seconds. The trial then continues according to method 700. During the trial, recipients are injected using the auto injector 250, 350 without being told which injectate they are receiving. Similarly, administrators are also not told which injectate each auto injector 250, 350 contains. In step 780, when the timer 420 finishes, the alarm 425 indicates that the injection has been completed and the auto injector 250, 350 can be withdrawn. This enables the injections to be administrated in the trial without revealing whether they contains the active injectate or the placebo injectate. Accordingly, those involved in the medical trial are unable to distinguish between the injectates. This is because, regardless of which injectate the auto injector 250, 350 contains, the alarm 425 indicating the end of the auto injector withdrawal time will be triggered after the same amount of time for every injection (18 seconds, in this example). As such, it is not possible to distinguish between an injection from an auto injector 250, 350 containing the viscid active injectate and an injection from an auto injector 250, 350 containing the inviscid placebo injectate.

-20 -As shown in the examples of figures 2, 3, 4A and 4B, the actuation system 100, 400 is integrally formed with the auto injector 250, 350. However, the actuation system 100, 400 may instead be a separate unit that is releasably couplable to an auto injector housing 260, 360. For example, the actuation system 100, 400 may form part of a cap that is placed over, and is attachable to, the auto injector housing 260, 360. For example, the cap may be attached to the second end 363 of the upper portion 361 of the housing 360. As such, the actuation system 100, 400 may be retrofitted to a conventional auto injector.

As shown in the example of figures 1, 3, 4A and 4B, the actuation system 100, 400 comprises the actuator 110, 410, timer 120, 420, and the activation means 130, 430 which are associated with each other so as to activate the actuation system 100, 400. In one example, the activation means 130, 430 is operatively coupled to both the actuator 110, 410 and the timer 120, 420. For example, as shown in the example of figure 4A, the coupling is physical -the rocker switch 431 (i.e., the activation means 130, 430) is physically coupled to the gear 422 of the timer 420 via the first leg 432 of the rocker switch 431. Similarly, the rocker switch 431 is physically coupled to the spring 480 (i.e., the actuator 410) via the second leg 434. However, the activation means 130, 430 may be operatively coupled to the actuator 110, 410 and timer 120, 420 in any other suitable manner.

Additionally or alternatively, the activation means 130, 430 may be communicatively coupled to each of the actuator 110, 410 and the timer 120, 420 such that communication signals can be sent from the activation means 130, 430 to the actuator 110, 410 and/or timer 120, 420. The communication signals are activation signals configured to activate the actuator 110, 410 and the timer 120, 420. The signals may be electronic or digital signals. The signals may be sent wirelessly. For example, instead of activating a rocker switch 431 with legs 432, 434, the coupling may be digital/electronic -a user may press a button (i.e., the activation means 130, 430) to trigger a first signal to be sent to the timer 120, 420 to begin timing and a second signal to be sent to the actuator 110, 410 to begin (i.e., releasing a compressed spring 480). In this example, the activation means 130, 430 comprises a printed circuit board configured to operate the signals. Accordingly, the activation means 130, 430 need not be physically coupled to the actuator 110, 430 and timer 120, 420 in order to activate the actuation system 100, 400. Instead, the activation means 130, 430 may be provided separately (i.e., physically remote) from the actuator 110, -21 - 410 and timer 120, 420. For example, the activation means 130, 430 may be part of a separate central activation device that is configured to send signals to the actuator 110, 410 and the timer 120, 420 to simultaneously activate them remotely. In a blinded medical trial scenario, an administrator may trigger a central activation device on their person to send such activation signals to the actuator 110, 410 and the timer 120, 420. The actuator 110, 410 and the timer 120, 420 are housed in an auto injector 250, 350 that is provided, and used, remote from the central activation device. The activation signals simultaneously activate the actuator 110, 410 and the timer 120, 420, thereby operating the syringe 270, 470 of the auto injector 250, 350 to inject a recipient. In other scenarios, the central activation device may be configured to activate a plurality of auto injectors 250, 350, each auto injector 250, 350 comprising an actuator 110, 410 and timer 120, 420 communicatively coupled to the central activation device.

In the example shown in figures 3, 4A and 4B, the actuator 410 includes a spring 480 to deploy the syringe 470 during operation of the auto injector 350. Alternatively, the actuator 410 may be any other suitable actuating member, such as a mechanical drive train, e.g., a screw-thread drive train, or an elastic tensioning system (not shown). The mechanical drive train works in an analogous manner to the spring actuator 480 of figures 4A and 4B. The activation means 430 activates the drive train simultaneously with the timer 420 (either a mechanical or digital timer), causing the drive train to apply a force to the syringe 470. In this example, the activation means 430 comprises a miniaturised electric motor (not shown) configured to operate the drive train upon activation.

In the example shown in figures 3, 4A and 4B, the actuation system 400 of the auto injector 350 includes a mechanical timer 420. However, in an alternative example, the auto injector 350 may instead include a digital timer (not shown). The digital timer may be any suitable digital timer that is compatible with an auto injector. The digital timer may comprise an integrated circuit configured to generate periodic signals to track the passing of time. Digital timer circuits are well known and will not be recited here for brevity. The digital timer may be battery operated, rechargeable or connectable to a mains supply. The digital timer may comprise a user interface with a display, such as an LED or LCD display, configurable to set and adjust the auto injector withdrawal time. For example, the user interface may comprise buttons configured to increase or decrease the auto injector withdrawal time.

-22 -Like for the mechanical timer, a digital timer is also activated by the activation means 430 at the same time as the actuator 410 (e.g., a spring 480 or screw-thread drive train). In this example, the activation means 430 may be an electronic switch or button, or another suitable activation means configured to activate an electronic timer and the actuator 410. Upon activation of the electronic switch or button, a first signal is sent to the electronic timer. This first signal triggers the start of the electronic timer to time the auto injector withdrawal time. Like for the mechanical timer, the auto injector withdrawal time is adjustable and settable by the electronic timer, for example by user input via the buttons on the user interface. At the same time as the first signal is sent to activate the electronic timer, a second signal is also sent to activate the actuator 410 and start the injection delivery time by releasing the actuator 410. Such an actuator may be a spring or a screw-thread drive train. In the example where the actuator is a spring, such as the spring 480 in figures 4A and 4B, the spring 480 is released by a leg that engages with a coil of the spring 480 in a similar manner to the second leg 434 of the rocker switch 431 described in relation to figures 4A and 4B. Upon receiving the second signal, the leg is moved from the engaged position to a released position such that the spring 480 is free to operate the syringe 470 -the compressed spring 480 begins to expand, applying a force to the syringe 470. Alternatively, the actuator 410 may be activated by a physical release leg, in a similar manner to the example shown in figures 4A and 43, without requiring a second signal to be sent. In the example where the actuator 410 is a screw-thread drive train, a first signal is sent to the electronic timer as described above. At the same time as the first signal is sent, a second signal is also sent to activate the screw-thread drive train and start the injection delivery time. The second signal activates a miniaturised drive motor that operates the screw-thread drive train to move the syringe 470 downward into its deployed position.

The alternatives described above can be combined in various arrangements of actuation systems for auto injectors. Accordingly, the actuation system 100, 400 may comprise any one of the following actuator/timer combinations: i) spring/mechanical timer, ii) spring/digital timer, iii) screw-thread drive train/mechanical timer, and iv) screw-thread drive train/digital timer. Other types of actuator 410 and timer 420 combinations may also be possible.

Claims

-23 -Claims: 1. An actuation system for an auto injector, the system comprising: an actuator configured for operating a syringe of an auto injector, the actuator having a first operating time that starts upon activation of the actuation system; a timer having a second operating time that starts upon activation of the actuation system; and activation means configured to activate the actuation system, wherein the actuator and the timer are activated by the activation means to start simultaneously upon activation of the actuation system, and wherein the first operating time is independent of the second operating time.
2. The actuation system of claim 1, wherein the timer is configured to generate an alarm at the end of the second operating time.
3. The actuation system of claim 1 or claim 2, wherein the second operating time is adjustable and/or preset.
4. The actuation system of any preceding claim, wherein the second operating time is equal to or greater than the first operating time.
5. The actuation system of any preceding claim, wherein the first operating time is the delivery time required for a dosage of an injectate to be fully administered to a recipient using the auto injector.
6. The actuation system of claim 5, wherein the first operating time includes the syringe's dwell time.
7. The actuation system of claim 5 or claim 6, wherein the injectate is one of a plurality of injectates, and the first operating time is the delivery time required for a dosage of the most viscous injectate of the plurality of injectates to be fully administered to the recipient using the auto injector.
8. The actuation system of any preceding claim, wherein the actuator comprises a spring or a screw-thread drive train.
-24 - 9. The actuation system of any preceding claim, wherein the timer is a mechanical timer configured to adjust and set the second operating time, and optionally wherein the mechanical timer comprises a timer spring, a gear, an escapement, a dial and an alarm 5 mechanism.
10. The actuation system of claim 9, wherein the mechanical timer further comprises a cap operatively coupled to the timer spring, and wherein the cap includes the dial, and the dial is twistable to adjust and set the second operating time.
11. The actuation system of any one of claims 1 -8, wherein the timer is a digital timer configured to adjust and set the second operating time.
12. The actuation system of any preceding claim, wherein the activation means comprises a switch or a push-button.
13. The actuation system of any preceding claim, wherein the activation means is communicatively coupled to the actuator and to the timer.
14. The actuation system of any preceding claim, wherein the activation means is physically coupled to the actuator and to the timer.
15. The actuation system of claim 13, wherein the activation means is physically remote from the actuator and/or the timer. 25
16. An auto injector comprising: a housing; a syringe positioned within the housing; and the actuation system of any preceding claim, wherein the actuator is configured to apply a force to the syringe to operate the syringe upon activation of the actuation system.
17. The auto injector of claim 16, wherein the actuation system is formed integrally with the auto injector.-25 -
18. The auto injector of claim 16, wherein the actuation system is releasably coupled to the housing of the auto injector.
19. The auto injector of any one of claims 16 -18, wherein the actuation system is operably coupled to the syringe.
20. The auto injector of any one of claims 16 -19, wherein the auto injector is configured to retract the syringe on or after the end of the second operating time.
21. The auto injector of claim 20, wherein the auto injector is configured to retract the syringe automatically or manually.
22. The auto injector of claim 20 or claim 21, wherein the actuation system is the actuation system of any one of claims 2-15, and wherein the timer is configured to generate the alarm at the end of the second operating time.
23. A blind trial system comprising: a plurality of auto injectors, wherein each auto injector of the plurality of auto injectors is an auto injector according to any one of claims 16-22; and the syringe of each auto injector contains an injectate of a plurality of injectates that have varying viscosities, wherein the second operating time of each auto injector is preset to be the same, and wherein the second operating time is equal to or greater than the delivery time required for the most viscous injectate of the plurality of injectates to be fully administered to a recipient using the auto injector.