FDA Outlines Personalized Medicine Policy with Publication of LDT Draft Guidance Document, Final Guidance on Companion Diagnostics

On July 31, FDA announced drastic changes to regulation for personalized medicine products and services when it coupled the release of the long-awaited final guidance document on the regulation of companion diagnostic devices with a proposed framework for regulating laboratory developed tests (LDTs), which was also long-awaited or long-feared, depending on your perspective.

The final guidance on In Vitro Companion Diagnostic Devices was welcomed by the personalized medicine community because in the document, FDA clarified the path for co-developed drug-diagnostic products, and finalized their assertion that new targeted therapeutics will not be kept from the market if the diagnostic kit is not ready at the same time. This enables promising new drugs to come to market while also allowing the laboratory community to fill testing needs in cases where an FDA-approved kit is not available for therapeutic selection, dosing and avoidance decisions.

However, many issues remain to be addressed.

To address concerns that FDA regulation will pose obstacles to an already challenged laboratory industry, there is a rather long transition phase — nine years — and an initial focus on high-risk. FDA defines high-risk LDTs as those with the same intended use as cleared or approved companion diagnostics, LDTs with the same intended use as an FDA-approved Class III medical device, and certain LDTs for determining the safety and efficacy of blood or blood products. This focus and transition period will allow clinical laboratories and FDA time to adjust. By focusing initial regulation on high-risk LDTs, FDA makes a strong argument for the framework, and slices off a rather small segment of the LDT market.

Many have argued that FDA does not have the bandwidth to regulate LDTs. FDA responded to this claim by reiterating enforcement discretion for the vast majority of LDTs and outlining a process for LDT regulation, which might be less onerous than traditional regulatory pathways for medical devices.

Although FDA made great efforts to address concerns about the Agency’s new regulatory enforcement, it did not address perceived conflicts between laboratory regulation under Clinical Laboratory Improvement Amendments (CLIA) and this new framework. Furthermore, FDA intends to use an expert advisory panel to provide recommendations to the Agency on LDTs risks and classification on certain categories of LDTs, as appropriate. I suspect that defining those categories will be contentious and, at times, difficult.

Investors have long argued that clarity is necessary in both regulation and reimbursement for continued advancement of personalized medicine. We now have clarity on FDA’s current thinking although many issues remain unresolved. The community has time to consider this framework and may soon have a chance to provide public comments. And finally, the pharmaceutical industry has the FDA’s assurance that targeted treatments will not be held up by co-development challenges.

BREAKING NEWS: FDA Notifies Congress of its Intent to Publish Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs)

Summers in D.C. are notoriously slow. FDA, however, has added excitement to this summer by informing Congress of its intent to publish a long-awaited framework for LDT regulation.

In its notice to Congress, FDA included what appears to be a draft of the document. After the mandatory 60-day Congressional review, the draft guidance document will be formally issued for public comment.

Within the draft framework, FDA proposes a risk-based, phased system of oversight. They recognize community concerns around access and do not intend to interrupt the marketing and sale of currently available tests. Furthermore, FDA expresses the intent to continue using enforcement discretion for forensic and organ transplantation uses, traditional LDTs, and LDTs for unmet needs.

The document outlines the history of LDT regulation, FDA’s policy of enforcement discretion, and how personalized medicine has caused FDA to reconsider that policy.

We will continue to provide updates on the development of framework for regulatory oversight of LDTs, with additional in-depth commentary next week on this issue and the related news of FDA’s final guidance on companion diagnostics.

For additional information on the current regulation of LDTs, please read PMC’s report “Pathways for Oversight of Diagnostics.”

Less May Be More

Personalized Medicine has come to be strongly associated with drug-diagnostic combinations (companion diagnostics).  While this is a very important aspect of personalized medicine, it is not the goal.  The goal of personalized medicine is to find the best possible care for each individual patient so as to maximize the likelihood of the individual achieving his/her personal life goals.  While this may seem obvious, this principle has become increasingly harder to identify in every day medical care.

A variety of different motivations has encouraged the healthcare enterprise to view illnesses, or even everyday complaints as the opportunity – if not obligation – to do something for the patient.  The better approach is to ask: What is the best thing one can do for a patient, including the possibility of doing nothing?

As we develop better drug-diagnostic combinations, this will become increasingly apparent.  Soon we will have the ability (through use of precise molecular diagnostics) to know with reasonable certainty whether there is little or no benefit for a particular individual to pursue a therapy which had historically been the standard of care.

But, are we truly ready to forgo a potential therapy even if such a decision is based on strong scientific data?  Or, will we continue to use a therapy on the off chance it might work?  Our desire to do something has to include the possibility that the best treatment might be no therapy, based on the risks to the patient, the likely benefits, and the life goals of the individual.  In the end, patients want their healthcare providers to help them make the best choice and personalized medicine can be a strong tool to do that.  This will provide the largest benefit for patients as they avoid the risks that come with all therapies when no benefit is realistically to be had.

Dr. Stephen Eck will be moderating a panel discussion on Wednesday, November 28, 2012 at the 8th Annual Personalized Medicine Conference in Boston, Massachusetts.  Join the discussion at #PMConf. 

Hamburg Highlights FDA Commitment to Personalized Medicine at PMC Annual Luncheon

When Dr. Margaret (Peggy) Hamburg delivered the Sixth Annual State of Personalized Medicine Address at the National Press Club on February 25, she impressed and energized the audience by announcing the Agency’s intent to release draft guidance on companion diagnostic regulation by the end of 2010.

As the PMC contends and she noted to the audience, for innovations to occur in personalized medicine, FDA needs to outline clear expectations and standards for approval.

According to Hamburg, FDA intends “to clarify our expectations for the kinds of clinical trials and levels of confidence needed to satisfy us that a test is accurate and that it can be used to help shape clinical judgments.…We also are working internally to make sure we have a common understanding across all centers and throughout the agency about the kind of evidence needed when a test result is being used to shape a drug trial, or drug approval or relabeling.  We also intend to make sure the communication line between sponsors and CDER and CDRH is clear, and that sponsors get consistent advice about how to take the next step in development.

We expect to have this guidance finished by the end of the year.”

She also promised that FDA would be flexible, collaborative, open, and clear throughout this process.   Hamburg concluded her remarks by sharing her enthusiasm and commitment for reducing regulatory barriers at FDA for personalized medicine.

Dr. Hamburg has clearly outlined sound goals – to articulate clear procedures and requirements within and among FDA centers for the approval of personalized medicine products– and a sound way to achieve them –through an open and collaborative process.  PMC members are excited by this commitment and are equally committed to working with her to this end since achieving these goals represents a necessary step in assuring that our regulatory processes are appropriately designed for the science of personalized medicine.

The full text of Dr. Hamburg’s speech is available here: https://ageofpersonalizedmedicine.files.wordpress.com/2010/03/pmc-luncheon_hamburg-speech_02-25-10.pdf.

Are We There Yet? Casting a Vision for the Future of Personalized Medicine

As part of their first issue of the new year, Nature ran a series of commentaries entitled 2020 Visions from leaders throughout the industry offering their predictions for what lies ahead in the coming decade. In his commentary on the future of personalized medicine, David Goldstein of Duke University recognized the following challenge, “Over the next decade millions of people could have their genomes sequenced. Many will be given an indication of the risks they face. Serious consideration about how to handle the practical and ethical implications of such predictive power should begin now.”

Dr. Goldstein’s admonition to consider the ramifications of personalized medicine for consumers is well warranted. Consumers have become increasingly informed and engaged in their health care, and the proper implementation of personalized medicine must include recognizing the impact this is already having on clinical care. There are also other significant challenges and opportunities that many are working vigorously to address, and will require additional effort in the coming months and years. To name a few:

• To what degree will personalized medicine be addressed in the final version of the health reform bill?
• Is personalized medicine ready to be adopted into clinical practice, or is there need for a greater scientific evidence-base? If so, what does that look like?
• Will federal incentives for the adoption of electronic medical records enhance the practice of personalized medicine, or impede its progress through implementation that is not aligned with personalized medicine?
• Are the efforts from biotech and pharmaceutical companies to augment their drug development pipelines with tailored therapeutics (and companion diagnostics) sufficient, or are we still relying too heavily on traditional drug development models?

In the coming weeks, this blog will feature commentaries from those involved in advancing personalized medicine and offer perspectives on what lies ahead. I invite you to share your predictions and expectations for the coming year and beyond. Many have recognized the potential of personalized medicine, but what must take place on the scientific, regulatory, political, or clinical levels to make personalized medicine a reality? I look forward to hearing your thoughts!

Companion Diagnostics Regulation Clarification: On the Horizon at the Food and Drug Administration

Federal regulation of diagnostic tests used in companion therapeutic-diagnostic products is seen by some to be a barrier for personalized medicine.  Others argue that definition of a clear, reasonable regulatory pathway for these tests will remove a barrier to personalized medicine. Today, drugs are regulated by one part of the Food and Drug Administration (FDA), lab kits (lab tests sold packaged in ‘boxes’) by another part of FDA, and laboratory test service companies are regulated by the Center for Medicare and Medicaid Services.  Companion diagnostics (lab tests and kits designed inform drug selection or dosage) pose a challenge to this system, and the opportunity to create a better one.

At the suggestion of the FDA, PMC convened a workgroup to suggest alterations to the agency’s 2005 white paper on the subject.  Stakeholders around the table sometimes had competing views, but all agreed that promoting high quality patient care is the central goal. This enabled the groups (including lab service companies, diagnostic kit manufactures, and pharmaceutical companies) to achieve consensus on several over-arching recommendations:

• Regulation must recognize the various types of companion products and work for all of them.
• Any oversight of in vitro diagnostic devices and laboratory-developed tests should be developed through an open and transparent process.
• Regulatory policy should promote rapid access to new diagnostic information to improve clinical care and sustain innovation.

Since FDA has suggested that it might pursue a series of white papers or hold a series of workshops on topics related to companion diagnostic regulation in advance of developing draft guidance on it, PMC also suggested a series of topics that might prove valuable to the community.  They are:

• Analysis of regulatory precedent for companion diagnostics.
• Review and analysis of evidence requirements for companion diagnostics and co-developed drug-diagnostic products.
• Intra-agency coordination among the office for drug regulation, the office for device regulation, and the Office of Combination Products.

The full text of the PMC’s submission to FDA can be found here: https://ageofpersonalizedmedicine.files.wordpress.com/2009/12/pmc-rx-dx-co-development-letter-to-fda-9dec09.pdf