Platform Drug Delivery Devices for Regulatory Submissions

Background and Scope

Manufacturers typically use a common device to deliver different drugs to patients. Co-development of the delivery device can involve significant resources, which need to be repeated for each product. Often, these activities are duplicative, but necessary, for generating safety and performance data on the combination product. The ability to use a platform device for multiple drugs has long been discussed as a potential avenue to create significant cost and time benefits for a manufacturer. Despite this need, development of platform devices has not received widespread industry or regulatory authority adoption. Challenges are myriad, including investment costs and the risk of regulatory authorities failing to accept platform data for use in clinical and marketing applications. Given that there is currently no regulatory pathway to receive review or approval of a platform device, the objective of this article is to describe how a platform device could be used to support approval of a combination product.

Manufacturers also implement their own hurdles that negatively impact the business case for platform devices (e.g., requiring redundant design control activities such as design inputs and design verification). Widespread use of the term “platform” in different contexts also leads to confusion about what is intended, causing another hurdle to successful implementation due to miscommunication between parties, particularly industry and regulators but also between industry partners. Building the case for regulatory and business acceptance is key and includes several objectives: align on the benefits of a platform approach, increase confidence in the robustness of device performance, reduce workload burden on regulatory reviewers and manufacturers, and expedite review of platform data.

It is also necessary to distinguish between leveraging data from an approved combination product toward a new combination product and platform device development. (Throughout this article, the term “combination product” is used to distinguish between a specific drug–device combination and a device platform.) Noteworthy is that leveraging product-specific data is not novel and is out of scope of this article. The objective is to outline concepts for prospective development of platform device data that can be repeatedly reused for multiple combination products.

It has long been common practice to repurpose an existing device for a new product. However, challenges can arise when these new uses are not part of the originally intended design and development plan, or if there was never a plan to leverage data from the start. For example, the original design can be stressed beyond its performance range, or the current engineering team may not fully understand prior design decisions, which may lead to unintended risks being introduced.

Widespread use of the term “platform” in different contexts leads to confusion about what is intended, causing another hurdle to successful implementation due to miscommunication between parties, particularly industry and regulators but also between industry partners.

However, none of this is beneficial if new products are unable to receive approval from health authorities. The objective is to pioneer the use of platform drug delivery devices by providing a clear definition, outlining a strategy for implementation, and discussing additional advantages beyond expediting premarket device timelines. The benefits of this effort arrive with the future uses of the platform, where the content can be leveraged for use on new combination products. For example, being able to reference the platform medical device file (MDF) should reduce effort that would normally occur when developing a new product. (The term “medical device file” is used in place of “design history file” because of global harmonization to ISO 13845.)1

Current Landscape

Three primary sources of platform technology uses exist in the regulatory space:

1. The EMA’s May 2019 draft guideline of the quality requirements for drug–device combinations2
2. The US FDA’s May 2024 draft guidance on platform technology designation programs for drug development3
3. The US FDA’s December 2019 draft guidance on bridging for drug–device and biologic–device combination products guidance4

Each of these documents provides definitions and insights into the regulatory use of platform devices. The EMA definition is broad and allows manufacturers to reuse data that has been previously characterized with appropriate discussion and justification.

The US FDA’s platform technology guidance states that although a device may meet the US FDA’s definition as a platform technology, devices generally would not fall within the scope of its Platform Technology Designation Program. However, the US FDA states that “ineligibility for designation does not preclude a sponsor from leveraging prior knowledge across applications.”3 The US FDA bridging guidance does not explicitly describe platform devices. However, the examples describe reuse of a device for multiple drugs as well as the regulatory and scientific considerations involved in assessing the applicability of the device data for multiple combinations products.

Analyzing these policy documents indicate that both the EMA and US FDA are open to the use of platform drug delivery devices and leveraging data, where supportable. The challenge is developing a platform strategy that is feasible to implement and is acceptable to regulators. Questions that need to be addressed include:

• To what extent can platform data be leveraged?
• When must a manufacturer produce new data for a specific combination product?

Platform Device Definition

A platform device is a drug delivery device, including its MDF and/or manufacturing processes, which are intended to be used for developing more than one drug–device combination. Differences in design, user interface, and manufacturing may occur for each individual drug–device combination to accommodate drug-specific attributes (e.g., dose, volume, concentration, viscosity, product differentiation, user population, indications for use, route of administration, environments of use).

Platform drug delivery devices share the following attributes:

• Common design features with prespecified drug delivery requirements and specifications that can be adjusted for specific drug–device combinations
• Test data demonstrating that the platform will meet its essential drug delivery outputs (EDDO) across the platform operational space (the term “essential drug delivery outputs” is used consistent with US FDA draft guidance)5
• An MDF that can be leveraged for each use of the platform
• A control strategy that can be scaled appropriately according to the combination product risk profile

The extent to which a manufacturer implements this terminology globally will determine which design features are included in the platform for use outside the United States. Various terms exist to describe the device’s drug delivery functions. For example, needle-based injection systems described in ISO 11608-1:20226 use primary function terminology. Other devices may have their own specific terms used to describe the device performance requirements related to drug delivery that are important in a technical or regulatory context, and these terms may have regional variations. Manufacturers of products marketed globally should keep these differences in terminology in mind when identifying and specifying platform device performance requirements.

Principles for Developing the Platform

The first principle for platform development is that any platform information being leveraged for a combination product must provide reasonable assurance of combination product safety and performance. The following guiding principles emerge from this:

• Any platform information being bridged must be applicable to the combination product.
• Any combination product safety and performance requirements not addressed with platform information can be addressed with information specific to the combination product.
• Combination product-specific risk analyses ensure that any gaps between platform and combination product are addressed.

These principles are implemented into a process whereby manufacturers can assess which aspects of the platform can be leveraged to a combination product.

Modular Approach to Combination Product Mdf Development

The concept of a platform is not novel. What is being presented here is a particular strategy for how to structure platform information and then use the platform for regulatory applications on a specific combination product. The proposed approach is modular, where each module serves a specific purpose and, when assembled, constitute the complete MDF for a specific combination product. A modular approach shown in Figure 1 provides a methodical approach to describing each part of a combination product MDF.

Any platform information being leveraged for a combination product must provide reasonable assurance of combination product safety and performance.

The platform module defines the design configurations that can be used for specific combination products, range of acceptable design inputs and outputs, design verification and validation data, and risk analyses demonstrating that the range of design inputs and outputs are satisfied. Collectively this is referred to as the “platform operational space.” The platform control strategy module is a set of control strategies specifically designed to assure the device quality.

The bridging module contains the information (e.g., analyses, data) to support the applicability of the platform module and platform control strategy module to a specific combination product, which is described in the combination product module. The combination product module contains all information required to be collected on the specific drug–device combination, including user needs, drug delivery requirements, design verification and validation data, risks analyses, and control strategies. The totality of these four modules constitutes a combination product-specific MDF.

What is being presented here is a particular strategy for how to structure platform information and then use the platform for regulatory applications on a specific combination product.

Platform Module

The platform module produces a set of documentation on the platform device that may be applicable to multiple drugs and that can be used to verify and validate performance of a combination product, including the following:

• Platform device identity
• Platform device design input and output requirements (i.e., the platform operational space)
• Verification and validation data on the platform device within the operational space
• Platform device risk analysis

Platform device identity

This includes identification and description of the device design, including components that are configurable for delivery of a specific drug.

Platform operational space

Engineers should think of the platform operational space as a multidimensional space where each dimension is a variable, including device design parameters, drug properties, and user interface requirements. The acceptable region is where the device meets its EDDO and safety requirements, without adversely impacting the drug or user interactions. For example, in an autoinjector, platform parameters might include drug viscosity, volume, spring force, needle gauge, biocompatibility of materials, and needle safety protection. The operational space will define combinations where the device delivers the drug accurately and safely. For example, multiple instances of an autoinjector-delivered drug may have variations in the spring, plunger rod, drug volume or viscosity, users, disease, or environments of use. These factors may result in product-specific variations that impact drug delivery performance and risk assessment. The design space should consider these potential variations and how the verification and validation data should be collected to provide relevant information to any combination product utilizing the platform.

The platform operational space will identify:

• Device design requirements for drug delivery (e.g., EDDO)
• Additional design requirements to be assessed (e.g., biocompatibility)
• Drug parameters that may influence device performance
• Representative configurations of platform device to be tested

Note that there are multiple possibilities for how a platform operational space is constructed and how representative configurations are selected. Engineering tools should be used to guide these decisions (e.g., design of experiments) and the justification for the applicability should be documented.

Platform data

Data are generated using representative platform devices to verify performance within the platform operational space.

Platform risk analysis

Complete a risk analysis on the platform device, inclusive of the platform operational space, knowledge of approved uses of the technology, similar user populations, and manufacturing processes. This information is useful to address device failure modes that will be common across all uses of the platform (i.e., failure mode and effects analysis).

Platform Control Strategy Module

The importance of platform control strategy lies in ensuring that the device meets consistent standards, is compatible with various drugs, and supports the safe and effective use of combination products. Given the device’s role in drug delivery, drug administration, or enhancing the patient experience, its quality is integral to patient safety and regulatory compliance.

The role of a platform control strategy is to provide a common set of controls that can support a specific combination product. Step one is to identify control strategy options for each EDDO. Step two is to select a control strategy for each EDDO, with options to scale (e.g., range of acceptable quality level by risk level) based on product-specific risks.

Bridging Module

The bridging module links the platform module to the device module. Its purpose is to rationalize the applicability of information from the two platform modules to a specific combination product. Information from the platform module and platform control strategy module are assessed in the context of information in a combination product module. This assessment is contained in the bridging module. Whereas the two platform modules are intended to be reusable, the bridging module must be uniquely developed for each specific combination product seeking to leverage the platform device because it provides the link from platform to product.

For example, although certain device specifications are likely always applicable because their performance is independent of the drug or users (e.g., performance of a needle safety protection feature), some specifications may only be applicable in certain intended uses (e.g., extended needle length of an autoinjector for adults vs. pediatric patients), and some will likely always require testing on the combination product (e.g., injection time on stability) because the performance is highly dependent on the specific combination product. The bridging module explains and justifies this analysis.

The bridging module serves to ensure the applicability of leveraged information into three categories, as depicted in Figure 2: directly applicable, bridging, and not applicable.

• Directly applicable: This category of information allows the use of platform information or platform control strategies directly to a specific combination product without any additional information required because that information is directly applicable on its face.
• Bridging required: This category of information allows the use of platform information or control strategies, with analysis to confirm applicability. This information may be used when the linkage from platform to product is explained.
• Not applicable: Platform information or control strategies are not applicable because they are not applicable to the specific product. Conditions of use, users, drug-specific factors, or other technical requirements do not support leveraging the platform. Therefore, product-specific information is required.

The development of platform drug delivery devices for combination products offers a transformative approach to drug delivery by enabling the reuse of device data across multiple drug and device combinations.

Combination Product Module

The combination product module contains two sets of information. First, it contains the device identity and EDDO performance specification. Second, it contains information identified from the bridging module that must be generated on the specific drug–device combination, including product-specific design verification and validation data, risk assessment, and control strategy.

Whereas the platform device may include many possible configurations of a device—such as different needle dimensions, springs, drive motors, and colors—the combination product module identifies the specific design configuration being used for delivery of a drug, including the identity of the device and its EDDO specifications.

The bridging module links information that is applicable to a specific product with the platform. Once the bridging assessment is completed, any remaining information necessary to demonstrate safety or performance of the combination product would be generated on the combination product itself. For example, confirming stability of the product can only be achieved by testing the product itself. Another example is human factors testing, which generally requires testing the proposed user interface with the intended user population.

Utility of a Platform Approach: Regulatory Strategies

Utilization of platform devices is ultimately only meaningful if manufacturers obtain regulatory approvals of a combination product based on platform information. Regulatory strategy is an important element in addition to the technical approach to platform development.

The first platform-based submission involves technical development of all four modules, in addition to regulatory strategy development. Each successive use of the platform follows the same form. However, the platform data and control strategy modules become fixed, whereas the bridging and combination product modules are revised for each specific product. Thus, the platform data and control strategy modules are constructed once and reused many times. Each specific product may have unique bridging considerations, resulting in differences in the combination product module information. Each product MDF (shown here in Figure 3 as product 1, 2, … n) is used to form the technical submission content.

A platform regulatory strategy can be implemented wherein a submission document can be authored and reused for successive product applications. Only the bridging and combination product-specific submission documents need revision for each specific platform-based product.

The roles of each module in a regulatory filing are described in Table 1. To operationalize this strategy, manufacturers can use different filing strategies. For example, creating a global electronic common technical document that can be reused (e.g., Module 3.2.P.4) across submissions. Manufacturers could also submit the platform module and control strategy as a master file (e.g., a US FDA device master file) or equivalent, allowing cross-reference in multiple combination product applications. The bridging and combination product modules would then accompany individual drug submissions (e.g., new drug applications or biologics license applications), cross-referencing the master file. Early engagement with regulators is critical to define the platform operational space boundaries and agree on bridging criteria, ensuring alignment on data reusability expectations.

This strategy accelerates development timelines and reduces costs by leveraging validated platform data. However, regulators must ensure that bridging studies adequately address drug-specific risks, and manufacturers must maintain rigorous change control to preserve the platform’s validated state. By adopting this modular, data-driven approach, platform drug delivery devices developed with regulatory applications submitted using the proposed platform approach can enhance innovation and patient access to combination therapies while upholding safety and efficacy standards.

Strategic Partnerships

The development of platform drug delivery devices for combination products often involves pharmaceutical manufacturers partnering with device manufacturers. There are opportunities for strategic partnerships, both with respect to design and development of the device and for the regulatory submissions to receive approval. One area for partnership is the development of the platform and the platform control strategy modules. During development, alignment on these activities, as well as the information necessary to make the appropriate bridging decisions, will be necessary to manage and address with partners. Similarly, alignment is needed on how to manage life cycle changes to the platform. Specifics of these issues should be formalized through written agreements with the suppliers.

Conclusion

The development of platform drug delivery devices for combination products offers a transformative approach to drug delivery by enabling the reuse of device data across multiple drug and device combinations. A modular approach not only has the potential to accelerate the approval process for new combination products, but it also enhances efficiency in addressing diverse therapeutic needs, provided that drug-specific interactions are rigorously evaluated. The discussion in this article highlighted practical strategies for engineers to optimize platform versatility and for regulators to assess data reusability, fostering innovation in patient-centric drug delivery systems.