One of the primary goals of the Innovation Pathway is to transform the experience for innovators working with FDA and for FDA working with innovators. In designing the Collaboration Phase we asked ourselves: Can a more collaborative culture lay down a new foundation for FDA's internal business processes? What would happen if FDA and the applicant worked cooperatively during the total product life cycle to create a shared understanding of both the developmental and regulatory processes?
Innovation Pathway 2.0 experiments with a different model of interaction and engagement between innovators and FDA. The Collaboration Phase, one of IP2.0's key features, is a mostly unstructured period that lays the ground work for deeper knowledge and a shared view of the benefits and risks of the product, allowing both parties to chart a regulatory pathway that is sensitive to time, and therefore indirectly cost. The amount of time spent in the Collaboration Phase is agreed upon by the applicant and the FDA at the outset (with a120-day maximum), giving flexibility for both sides to strive for agreement, and allowing a customized approach for each company. While FDA retains responsibility for regulatory decision-making, the intent is to arrive at these decisions in a collaborative way.
The guiding principles behind the Collaboration Phase include creating a shared understanding of product success including its benefits and risks, creating solutions that facilitate forward progress, allowing experimentation, prototyping, and learning, and striving for greater transparency.
Successful components of the Collaboration Phase are expected to drive the business processes used by FDA and are intended to be supported and enhanced by the information technology infrastructure.
Case Studies of the Collaboration Phase
The following three case examples are used to illustrate the philosophies, features, and processes of the Collaboration Phase.
"GemMedix" is a start-up company that has developed an innovative monitoring system intended for consumers, and has been accepted onto the Innovation Pathway. A venture-funded company, they are early in the prototype phase and have performed engineering and animal testing that demonstrates proof of principle. They are unclear whether certain features of the product are regulated by the FDA. For the features that are regulated by the FDA, there does not appear to be a predicate.
For the Collaboration Phase, GemMedix and FDA agree to bi-weekly interactions over a 60-day period, with the goal of getting clarity on the regulatory pathway. Since the company is based in Seattle, meetings are conducted through videoconferencing with the FDA team. Organized and facilitated by the FDA case manager using best-practices for meetings, the early interactions serve to educate both FDA and the company, peer-to-peer, on both the device and various regulatory approaches which could lead to device marketing. GemMedix ships two prototype devices to the FDA team and shows a video demo of how the product will be used by consumers. Subsequent meetings include FDA's program operations staff and a policy analyst to tackle issues related to product classification. Over the course of several meetings, a regulatory pathway is established along with a rough estimate of the timeline for future interactions.
GemMedix remains concerned that one part of the proposed regulatory pathway will considerably delay market entry. Recognizing this is a critical decision point, the FDA or GemMedix review team can request higher level FDA review at this time.
Using a prototype collaborative workspace, GemMedix and FDA create the documents that will serve to capture the key decisions reached during collaboration. At the end of the Collaboration Phase, FDA converts components of these into a completed pre-IDE application for the purpose of documenting and archiving the material, and the appropriate reference letter is sent to the company. The collaborative workspace remains open for future interactions and linking of key documents among team members.
The GemMedix and FDA team members answer a satisfaction survey at the end of the Collaboration Phase, which results in constructive suggestions to both sides.
"Spectrum" is developing an implantable technology for patients with autism. They have conducted extensive safety studies on animals and previously submitted a pivotol IDE to FDA that had been disapproved. Because this technology represents medical device innovation addressing clinical needs and improved patient care, and alternative treatments are unavailable, Spectrum is accepted onto the Innovation Pathway.
Spectrum and FDA agree to a 45-day Collaboration Phase during which there will be extensive discussion of initial clinical insights and the data necessary to support an early feasibility study. The FDA case manager suggests consultation with the Network of Experts to propose a device evaluation and trial evaluation strategy to best describe the device and procedure-related attributes and also to address the potential failure modes.
Working together, patient and caregiver needs are identified and tied to the possibility of technology addressing them. There is a shared concern and discussion about the risks of this technology, as well as the benefits it could bring.
The Spectrum and FDA team members use a prototype "decision tool" that steps them through the expected risks and benefits for the device when used in patients with autism. Previous discussions with caregivers and patients help to establish clinically relevant trade-offs between risks and benefits and become part of the decision framework. This exercise helps the team generate a common understanding of the minimum evidence FDA needs to make decisions at key stages: 1) at the time of IDE submittal for the first in human trial; 2) at the time of IDE submittal for the pivotal trial; and 3) at the time of premarket submission to support the approval decision. Should the PMA be approved, the decision framework would then be incorporated into the published Summary of Safety and Effectiveness, making public the basis on which FDA's benefit-risk determination was made.
In response to an Innovation Challenge, several companies developing similar technologies are accepted on the Innovation Pathway, each at different stages of development. Each company is working separately with FDA during their respective Collaboration Phases. However, because they will share similar regulatory challenges, FDA opens a public collaboration workspace to post questions and answers. With permission from each company, specific regulatory issues are converted into generic questions for open discussion, allowing applicants to contribute to the developing opinions.
During the course of the Challenge, FDA hosts a virtual workshop for all participants. The virtual workshop is a public, moderated conversation with subject matter experts both inside and outside the agency.
Guiding Principles for the Collaboration Phase
The following guiding principles, which are used in the case examples, serve to define the "rules of engagement" among the participants and FDA.
Principle 1: Share an In-Depth, Common Understanding of Success
The Collaboration Phase is intended to provide sufficient unstructured time between the applicant and FDA to allow experiential learning about the product, including hands-on interaction through manufacturing and health care facility site visits, in-person demonstrations of the new device, and/or video demonstrations, etc. Using best practices in idea exchange, such as IT tools that promote collaboration, document sharing, conversations, and peer-to-peer interactions, this period drives toward the goal of generating a shared understanding of the product. Leveraging outside experts through FDA's Network of Experts can enrich the dialogue and more quickly identify and resolve important scientific questions.
Principle 2: Apply Best Practices in Framing Benefit and Risk
To assure that decisions are based on an appropriate balance of benefit and risk, teams will work from a number of guidance documents, including the following (which currently exist in draft form, and therefore will be implemented when finalize):
- "Draft Guidance for Industry and Food and Drug Administration Staff — Factors to Consider when Making Benefit-Risk Determinations in Medical Device Premarket Review,"
- "Draft Guidance for Industry and Food and Drug Administration Staff — Investigational Device Exemption (IDE) for Early Feasibility Medical Device Clinical Studies, Including Certain First in Human (FIH) Studies,"
- "Draft Guidance for Industry, Clinical Investigators, Institutional Review Boards, and Food and Drug Administration Staff - FDA Decisions for Investigational Device Exemption (IDE) Clinical Investigations," and
- "Draft Guidance for Industry, Clinical Investigators, and Food and Drug Administration Staff - Design Considerations for Pivotal Clinical Investigations for Medical Devices."
In addition, teams will work with a decision support tool at appropriate points in the regulatory pathway. To understand the product in the context of current clinical practice, and to the evaluation of benefits and risks, teams will incorporate patient, caregiver, and physician perceptions of the benefit-risk trade-offs into decision-making.
Principle 3: Create Solutions that Facilitate Forward Progress
During the Collaboration Phase, the team shares responsibility for developing a pathway that is least burdensome and predictable while allowing for some measure of flexibility, understanding that some issues are within FDA's control to address, some can only be influenced, and others are not within FDA's sphere of influence. Regardless of FDA's level of control we proactively commit to share with innovators the responsibility to reduce the cost and time from development to market without changing our approval standard of reasonable assurance of safety and effectiveness or our evidentiary standard of valid scientific evidence. Critical decision points are approached in a way that permits re-examination of past precedents and allows new approaches. Critical decision points might include: device classification, de Novo versus PMA, significant risk versus non-significant risk clinical trials, and pre-market versus post-market evidentiary requirements.
Principle 4: Improvise, Experiment, Prototype, Test, and Learn
The Collaboration Phase results in a pathway that is customized based on an on-going discussion with the company. The charted pathway is allowed to "fail fast" by promoting frank assessment of it as it is traversed, and allowing adjustments to be made as necessary. Surveys of the participating innovator and FDA staff conducted at critical points are intended to provide more regular feedback to both sides, helping to de-stigmatize the feedback process and encouraging the team to learn.
Principle 5: Full Transparency in Decision Making
Because of the collaborative nature of this phase, the innovator should have a clear picture of how FDA intends to make critical decisions about the product's trajectory through the regulatory process. By allowing critical decisions to receive higher level FDA review, the process is intended to reduce uncertainty about future decisions. Prior to market approval, documents supporting the decision-making framework can be viewed and discussed between the innovator team and FDA. At the time of approval, portions of these documents will be incorporated into the published Summary of Safety and Effectiveness (for PMA devices) to allow transparency of process. The team will also work collaboratively with other experts to develop new guidances or update existing guidances, providing a more predictable pathway for future applicants.