TECHNOLOGY AREA(S): Bio Medical, Bio Medical, Chem Bio Defense, Chem Bio DefenseOBJECTIVE: To design, develop, and manufacture appropriate sized autoinjector containers that are able to contain and deliver greater than or equal to ( ≥ 0.7 mL ) and less than or equal to( ≤ 2.0 mL ) formulation volumes. Containers must be chemically inert to prevent drug formulation interactions and potential degradation of active ingredients. The containers need to resist damage during manufacturing and improved field survivability. Containers may be composed of strengthened glass or made with reinforcing coatings or other barrier coating systems over traditional glass or plastic. The containers will facilitate the generation of drug autoinjectors with a minimal rate of failure, and able to meet rigorous FDA medical device standards and requirements.DESCRIPTION: Chemical agents, such as organophosphorus nerve agents (OPNAs) and other non-traditional chemical agents of concern, can exert their life threatening effects within a short period of time after exposure. Exposed individuals require immediate delivery of medical countermeasures to improve the chances of survival after a chemical attack. Medical countermeasure autoinjectors are critical medical devices that allow timely delivery of lifesaving medications in austere environments, outside of the medical care setting. While civilian autoinjector devices can be stored properly to ensure maintenance of device integrity and medication stability, fielded military autoinjector devices must be sufficiently robust to ensure the device is available at a critical time point. Hence, improvements are needed in autoinjector device design, to include both components and materials, to increase reliability and ruggedness. Military medical countermeasure autoinjectors rely on chemically inert containers to hold the drug formula being delivered in parenteral injections. Additionally, the FDA requirements for the reliability of combination drug/device products fit for purpose are stringent.However, currently available glass containers can be damaged either in shipment, or handling during manufacture, or while the autoinjector is being deployed or operated. This damage can contribute to container failure during the assembly process or potentially contribute to a failure of a fielded device. Improved, chemically inert containers that are resistant to these failures would aid in generating military autoinjectors that are more reliable and rugged.Low internal energy following annealing has been identified as the root cause of cracked glass parenteral containers (1).The glass breakage mechanism is crack propagation by tensile stress concentration at a damaged point on the glass.This point serves as an origin of the breakage (2).The objective is to create containers that are resistant to these known failure mechanisms.The desired parenteral container should withstand insults from the manufacturing, filling, and assembly processes but still be conducive to an autoinjector design.The Department of Defense (DoD) is interested in identifying various potential solutions to achieve this objective. Innovative solutions may include, but are not limited to: 1) Changing the dimensions and thickness of the glass container.Making the areas of the envelope less vulnerable to damage by making them thicker may provide the needed strength to withstand manufacturing assembly, abuse in handling the device during operations, and the subsequent firing of the product when and as needed.2) Treatment of the container, or the vulnerable areas of the glass container, with strengthening procedures.This can include well developed treatment approaches such as strengthening, tempering and ionic treatments; as well as novel/technology solutions that can be successfully applied to the containers. 3) Change container materials to stronger glass or adding barrier coating systems, such as polymer films, to augment strength. A pharmaceutical glass is reported to provide superior resistance to damage (1).4) Change the container materials to plastic and treat the drug contact areas with a barrier coating system such as silica.An important parameter to consider is that changes in dimensions should take into consideration the availability of standard components that are used in the assembly of autoinjectors, such as plungers that push the drug out of the container and container sealing caps. Containers used for injection of medical countermeasures typically follow an ISO 11608-1 D1 single dose container system designation.ISO 11608-3 specifies the functional and design considerations for containers to be used with needle-based injection systems (NIS) that fulfil the specifications of ISO 11608-1 (4).In Section 4.4.2 of ISO 11608-3; 2012 (E), Figure 2 shows the dimensions for typical cartridges used as D1 containers for these military systems.For containers that are able to contain and deliver greater than or equal to ( ≥ ) 0.7 mL and less than or equal to ( ≤)2.0 mL, the dimensions d_6, d_2 and l_3 in Figure 2 need to be adjusted to satisfy the volume ranges, but provide adequate serviceable strength without evidence of damage.PHASE I: Due to the range of potential solutions/approaches that can be explored, there will be some flexibility in the milestones that will be accepted for this Phase. Objectives for this Phase are: 1) Determine if vulnerable areas of glass container can be sufficiently strengthened by thickening the glass to prevent catastrophic failure of the container closure system while staying within a maximum dimension l_3 of 53.3 mm (2.1”) and diameter d_6 of 8.7 mm (0.34”) for the smaller, and a maximum dimension l_3 of 53.3 mm (2.1”) and diameter d_6 of 11.6 mm (0.46”) for the larger.The containers to be designed, should be able to contain and deliver ≥ 0.7 mL and ≤ 2.0 mL formulation volumes.Final lengths and outer diameters may need to vary slightly to match existing designs. Alternatively, a design can be advanced that focuses on plastic containers treated with a barrier coating system such as silica to prevent interactions with the pharmaceutical product. 2) Advance towards generating prototypes that can be tested to demonstrate higher reliability and ruggedness than the current military container closure systems. 3) Plan to advance from prototype generation (Phase II) to rigorous testing. 4) Provide an estimate cost per unit to determine how the container will impact cost per autoinjector unit. Objectives may be met using mechanical simulations that model the physical behavior of a container incorporating the proposed solution/material/treatment versus the current container design/materials.PHASE II: Strengthen currently used containers (stay within maximum l_3 and d_6 dimensions) using toughening treatments such as thermal ionic transfer, or laser surface modification, or other technologies identified/selected. Alternatively, continue development and testing of plastic containers treated with a barrier coating system such as silica.The optimized container configurations, reinforced or new prototypes, should be tested to military standards to quantify the degree of shatter resistance each approach offers.In addition to prototype and test data, the small business offeror should perform a cost impact assessment for the method(s) being employed to update the preliminary estimate.An additional objective for this Phase is to provide a plan to achieve production levels required to support autoinjector manufacturing.PHASE III: Coordinate with multiple autoinjector manufacturers that supply, or will be supplying in the future, autoinjectors to the DoD, to incorporate improved container design into the assembly process. The improved container will demonstrate the ability to provide superior container closure system performance to help to satisfy the Food and Drug Administration’s (FDA) rigorous reliability requirements for the assembled autoinjectors. This will require sufficient quantities of the improved container necessary to conduct stability testing and determine with appropriate test methods at industry standard time-points if regulatory requirements and standards are achieved.PHASE III DUAL USE APPLICATIONS:The improved/strengthened autoinjector vials have multiple applications and multiple end-users. Specifically, in forward fielded medical encampments during natural disaster responses, this product will be extremely useful to minimize failures during long-distance, expedited shipments.These types of supplies are critical for patient care, and maximizing 100% of product shipped must be available for use at the Point-of-Care.This is also true for the first responder/Emergency Medical Technical (EMT) communities when responding to a variety of medical emergencies include administering antidotes for drug overdoses. KEYWORDS: autoinjector, glass strengthening, drug containers, glass ionic transfer, pharmaceutical glass, glass coating, glass treatment, chemically inert polymer, drug deliveryReferences:1. Enhanced Patient Safety through the Use of a Pharmaceutical Glass Designed to Prevent Cracked Containers. Schaut R, Hoff H, Demartino S, Denson W, Verkleeren R.PDA, Inc. (2017).2. Fracture Analysis, a Basic Tool to Solve Breakage Issues. Ono T, Allaire R.Corning Technical Information Paper 201 (November 2004).3. A Method to Quantitatively Define and Assess the Risk of Cosmetic Glass Defects on Tubing Glass Vials. Loui A.PDA, Inc. (2011).4. ISO 11608-3: 2012, Needle-based injection systems for medical use — Requirements and test methods—Part 3: Finished containers.
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