To accelerate products to market, OIVD needs to take the following actions to improve transparency.
First: Issue a Blue Book memo stating that the Product Development Protocols (PDP) process is a desired outcome for new technology development, and change the existing guidance below to read “..technology is not well established…”
In the product development protocol (PDP) method for gaining marketing approval, the clinical evaluation of a device and the development of necessary information for marketing approval are merged into one regulatory mechanism. Ideal candidates for the PDP process are those devices in which the technology is well established in industry. The PDP process provides the manufacturer with the advantage of predictability once the agreement has been reached with FDA.
While industry cannot expect dictated clinical evaluation requirements, there is enough history for OIVD to be able to negotiate the requirements. This would meet the objective of transparency. Since FDA has not encouraged the PDP process, the proposed Blue Book memo should state that any hesitation by a review branch will call for prompt investigation by higher management or the ombudsman.
Having senior FDA management drive this type of cooperative clinical-requirement transparency would change the culture of the Class III approval process and bring more accountability to the branches. With an IVD PDP in place, including a package insert with preapproved indications for use, all that would be missing would be the completion of the data tables. The regulation states, “A PDP that has been declared completed by FDA is considered to have an approved PMA (§814.19).” In summary, FDA management needs greater encouragement to negotiate binding clinical requirements to support Class III novel technologies.
Second: Outside of the Class III PDP process, senior management should update the CDRH meeting guidance to encourage binding agreements for Class II clinical protocols. There is no reason that such formal agreements should not be an expectation of sponsors and the public.
Third: If the U.S. diagnostic clearance and approval system is to be retained, then the diagnostic 510(k) process should be defended—especially the de novo approach—emphasizing the differences between diagnostics and other devices. With the protections offered via the physician order, laboratory director supervision, and CLIA, establishing substantial equivalence and the potential risk for a diagnostic does not compare to other devices. In fact, it has long been OIVD policy that improvements in technology per se do not interfere with a substantial equivalence determination as long as the new technologies do not create new issues of safety and effectiveness. Looking back at the evolution of urine glucose to capillary blood glucose, RIA to EIA, polyclonal antibodies to monoclonal, and microbial culture testing versus amplified NAT, the biggest challenge of the 510(k) process has been convincing OIVD that improvements in sensitivity and specificity are valid in these newer technologies and not false positive/negative results. Technology improvements should not impede the IVD 510(k) process.
Fourth: The concept of “enforcement discretion” needs outside examination through public meetings and/or congressional oversight. OIVD should not state that new initiatives, like in vitro multivariate index assay (IMDMIA) products, are a priority without issuing a plan and a timeline for publishing an updated draft guidance, a final guidance, or a regulatory proposal. Priorities without timelines are anathema to transparency.
Finally, should the current system to move diagnostic products to market be defended or strengthened? Or should it be radically changed? A close examination of the laboratory developed test (LDT) process alongside the 510(k) and European IVD Directive indicates to some that the FDA diagnostic processes may be overkill. Serious consideration should be made to either downgrade the OIVD process to mirror the LDT or IVD Directive processes, or level the playing field and add oversight to the LDTs. (There is no significant adverse safety data supporting the latter.) The status quo of enforcement discretion is indefensible. Without transparency in enforcement, FDA actions are publicity or subjectivity driven. This is not how a scientific organization should enforce the law.
In summary, two proposals are being made for OIVD transparency: model on the EU system for IVDs or work with industry on binding submission expectations.
is president of RCQ Consulting (San Diego, CA) and a member of IVD Technology’s editorial advisory board. He can be reached at email@example.com.