Design Controls For Drug Delivery Devices, Part 1: A Process Primer

By Fran DeGrazio, executive editor, Drug Delivery Leader

A concerning trend I have noticed over the last several years is the increasing number of experienced scientific and technical personnel transitioning from biopharma to retirement. Their departure makes clear that the knowledge drain is real. For that reason, frankly, there needs to be a focused effort on educating those still in the industry, especially those much earlier in their careers. As an industry veteran myself, it is my intent to periodically use forums like this one to give back to the industry by providing foundational information to those whose industry experience may have thus far left key knowledge gaps.

One of the most critical topics for knowledge-bolstering is design controls. In the development of combination products and other drug delivery devices, Design controls ensure that the results of product development processes meet user needs and specified requirements. This article will lay out some of the most basic and, therefore, fundamental concepts. In a follow-up article, I will return to the topic of design controls to offer recommendations and tips for implementation.

QbD Is Not Design Controls

Design controls are crucial for combination product and medical device development, as mandated by various FDA regulations, such as 21 CFR 820.30 and an associated FDA guidance entitled Design Control Guidance for Medical Device Manufacturers. Additionally, ISO 13485 outlines design controls as part of section 7.3. However, individuals whose industry experience has been primarily in pharmaceutical development may be acquainted with control-related concepts such as Quality by Design (QbD) but may not be familiar with design controls for devices. A recommended practice for developing drug products, QbD shares similarities with design controls in being risk-based and in focusing on quality from the beginning rather than solely relying on testing at the end. However, in addition to using differing terminology, QbD is not mandated by law. Because, in my view, the future of drug delivery is in drug-device combination products; understanding only the pharmaceutical side of things is not enough.

The End Goal Of Design Controls

Design controls begin with planning and documenting development, starting  with the identification of user needs as a means to ensure a focus on the ultimate end goals. In my 40 years in industry, I have found that one of the biggest mistakes in product development stems from engineers designing products based on a  “cool” technology and not on an actual, known user problem or challenge. An example is the historical development of on-body injection (OBI) systems. Initially, the physical size of these systems was not considered a priority. Now, however, it is widely recognized that the size of the device is crucially important to adoption and effectiveness, as patients prefer wearables that are unobtrusive and do not interfere with routine activities.

Patient safety is another key consideration when injecting design controls into the product development process. Prioritizing patient safety as a way of ensuring freedom from unacceptable risk makes Risk Management an essential component of Design Controls and vice versa.

The Roles Played By Design Inputs And Outputs

The next two key process steps involve a) developing design inputs, which are quantifiable attributes that can then b) be converted into design outputs. Design inputs are translated from the user needs. For instance, a user of an injection device may require a non-auditory means of confirming injection completion. The corresponding design input could be “Electronic display lights up upon injection completion.”

Design outputs are the results or deliverables of the design process. These verify the design inputs and should reference acceptance criteria. Design outputs can vary and  include functional and performance considerations, specifications, labeling, and other related aspects. As a simple example, during the initiation of an injection from a prefilled syringe, the user would depress the plunger. The goal is to have an accurate dose volume. The break loose and extrusion of that plunger in the syringe system is one of the  drug delivery design outputs that can be tested and reported in support of the user need.

 Ultimately, the design outputs become part of the Device Master Record (DMR). The DMR includes everything that you would need to build and test your device and is critical from a regulatory compliance standpoint.

During development, design outputs will be understood and essential design outputs identified. This identification of which outputs are essential is a critical step and one that is necessary in order to satisfy regulatory requirements. In June 2024, FDA released a draft guidance entitled Essential Drug Delivery Outputs for Devices Intended to Deliver Drugs and Biological Products. Drug Delivery Leader has produced two online live events on the guidance. I co-hosted and moderated both featuring expert panelists Susan Neadle and Alan Stevens. The second one, entitled EDDOs Revisited: Putting Essential Drug Delivery Outputs into Practice, provided further clarity on translating the draft guidance into real-life application and included several case studies.

The Criticality Of Design Review

Another critical step is design review, a formal evaluation in which the product  and its development process are reviewed to assess adherence to requirements, functionality, effectiveness, and other factors. Design reviews must be formally documented to indicate that the design and its associated processes have been thoroughly evaluated. These would be completed by an independent employee or consultant who supports the project.

As part of the review, feedback on existing or potential issues should be provided to the designers. The review process confirms that the design is ready to proceed to the next stage. I have found the feedback step to be critical to satisfactory execution because the project engineers may naturally want to keep moving forward even if problems exist. An objective reviewer helps to hold the team accountable and can either delay approval or move product development to the next phase.

Following design review, the final stages of formal development include design verification and design validation. Design verification demonstrates that the design outputs meet the design inputs as specified. It confirms that the product was designed according to the intended requirements. Design validation confirms the product design suits its intended users and, therefore, is crucial in proving the product’s appropriateness for them. After design validation, the product is then transferred to manufacturing.

From Design Controls To Change Controls

Design controls and change control work together. Design controls manage the design process while change controls ensure that any changes made during development or later are documented, reviewed, and approved. Change control is important during both development and post-industrialization. Once a product is placed under a design freeze, in order to stabilize the design, changes and their rationale should be documented

Frankly, the above primer on design controls is a greatly simplified version of the process. However, for those still on the learning curve and for those appreciating a refresher, it demonstrates the foundational design controls steps for achieving compliance during device and combination product development.

In a follow-up article, “Design Controls For Drug Delivery Devices, Part 2: A Practical Perspective,” I will focus on design controls implementation practices and provide examples of challenges and solutions in execution.