FDA Releases Proposed Guidances For Next Generation Sequences

Last week the Obama Administration released one of its periodic fact sheets announcing recent actions on the Precision Medicine Initiative (PMI).  The PMI is trying to build tools and gather data to make it easier to target therapies and other medical treatments for specific individuals.

Part of this latest fact sheet is the announcement that the Food and Drug Administration (FDA) is releasing draft guidance on oversight for what’s called next generation sequencing (NGS).  This category of tests measures a much higher number of genetic variants than current sequencing.  The agency believes that these draft guidances – one on standards for analytical validity of NGS tests and another on using evidence from public genome databases to demonstrate the clinical validity of NGS tests – can be sufficiently flexible for a family of tests that is emerging and notably distinct from existing sequencing and related tests.  This is a situation where the agency likely believes that establishing some boundaries for a new testing field can support the development of such tests.

If you’re interested in providing comment on either draft guidance (or both), you will need to submit them by October 6.

Congress Likely To Punt On National GMO Labeling Legislation

Vermont passed a law in 2014 requiring that grocery food labels will need to declare if the products contain ingredients that were genetically modified.  The law is scheduled to go into effect on July 1, even with a pending lawsuit in federal court.  As the market in Vermont is relatively small, it is not economically feasible to print labels just for products sold in Vermont, which will effectively make the Vermont labeling law a national standard…

Unless Congress does something by July 1, or other states enter the labeling space and offer their own bills.

As you might guess, the chances of Congress acting by the deadline are relatively slim.  An effort to prevent state GMO labeling laws failed in March.  There are efforts underway to find a way forward, but with a limited number of legislative days before July 1, there might not be enough time.  Given that the Secretary of Agriculture and major food producers are interested in a national standard (if for no other reason than to avoid a patchwork of several different state laws), I think this is another example of the willingness of Congress to not do its job (see the annual tragedy of the budget process for the first, best example of this negligence).

For the record, my personal position on this is much like what the General Mills executive outlined in the blog post I cited earlier.  I think GMO food products have been demonstrated as safe for human consumption, but I also think it reasonable to label products with GMO ingredients.

Research Mice Are Strongly Segregated By Sex

Earlier this week, when discussing the recently implemented National Institutes of Health (NIH) grant requirement that proposals cover how sex is accounted for as a biological variable, I commented on the length of time it has taken to get to this point.

“While some of this time can be accounted for by the typical time required in developing policy I think it also highlights the challenges in confronting and mitigating a longstanding bias against systematic consideration of sex in biomedical research.”

I mentioned in that post a 2015 GAO report noting the problems NIH grantees have had in incorporating women into clinical trials.  However, this Nature news article describes the problems ahead for addressing sex differences in research animals.  It discusses a paper in eLife that describes an analysis of sex differences in research mice used in over 15,000 open access research papers published between 1994 and 2014.

While researchers did find that recording data on animal studies improved over the time series of the study, it plateaued around 2010.  So the existence of subsequent policies, like that of the NIH, has not yet translated into further improvements.  The study also noted that certain research fields have strong preferences for either male or female research mice.  These differences were also found in different kinds of research in the same field (the Nature article notes that diabetes research tends to use male mice, but studies on immunology related to diabetes tend to use female mice.

It would seem that policies will only be one tool used in order to successfully manage the use of both genders in research mice for biomedical research.  Education and journal practices will need to adapt to make sure researchers understand why sex is an important variable in their research that needs to be address much better than it has until now.

Work Continues On Including Sex Differences In Biomedical Research

Back in 2014 the National Institutes of Health (NIH) announced that it would be taking steps to ensure that research involving lab animals and research cells would reflect the same gender standards required for research involving human subjects.  At the time there were no official changes made to research regulations, but the NIH started a process of communication and discussion with researchers and other stakeholders about how to better account for both males and females in their research.

Now things are being formalized.  Effective with grant applications due on or after January 25, the NIH is requiring projects be evaluated for how the proposals treat sex as a biological variable.  If the project is focusing on only one sex the proposal must provide a strong justification based on the scientific literature, preliminary research data or other relevant factors.  The NIH has provided guidance, with pointer to relevant sources, for complying with the new policy.

It has taken nearly two years to move from initial announcement from NIH to first requirements that sex as a biological variable is important in research.  While some of this time can be accounted for by the typical time required in developing policy I think it also highlights the challenges in confronting and mitigating a longstanding bias against systematic consideration of sex in biomedical research.  As noted in this 2015 GAO report, the agency has had trouble in effectively integrating data from women in clinical trials.  I think it plausible that similar challenges face the integration of both sexes in animal and cell research.

Is CRISPR Dual-Use Research Of Concern?

Today the federal government released its proposed budget for Fiscal Year 2017.  (The year is scheduled to start on October 1st, but this budget isn’t likely to be passed until close to calendar year 2017.)  But it wasn’t the only government release of note.

One item that caught my attention is in the Worldwide Threat Assessment that the U.S. Intelligence Community issued by the Director of National Intelligence James Clapper (H/T MIT Technology Review).  On page nine of the report (page 13 in the digital file) there is reference to recent meetings in the U.S. and Europe that express concern over the unregulated use of genome editing technology.  CRISPR is not named in the report, but that specific technology was the focus of at least one international meeting.

The concern expressed in the report is on the relative ease and reduced cost of being able to conduct the work.  The deliberate or unintentional misuse of this technology could pose national security risks depending on the applications.  The report lists genome editing in a section on weapons of mass destruction (WMD), which suggests that the intelligence community is concerned about this work either being weaponized or (more likely) used to develop particularly nasty biological material.

While the report notes that there are still technical hurdles in existing genome editing systems, I think the mention of genome editing as a technology worth monitoring by the intelligence community raises some new regulatory interests, at least in the U.S.

Genome editing technologies could be classified (at some point in time, if not now) as dual-use and therefore subject to additional scrutiny.  There currently exists a government policy for life sciences dual-use research of concern, but it is focused on particular biological agents and/or toxins and CRISPR or comparable genome editing technologies would only qualify if the purpose of such experiments or the agents and/or toxins already is covered by the policy.

And I think this is a challenge with genome editing.  As I understand it, the advantage of CRISPR and comparable technologies is radically improving the speed and accuracy of what is already being done.  That may change if the new genome editing technologies demonstrate the ability to do some kind of genome editing previously impossible.  We aren’t there yet, but the intelligence community thinks that time is on the horizon.

Public Sessions Announced For Input On Revising Biotechnology Product Regulations

In the summer of 2015 the Obama Administration announced a process to update the regulatory system for biotechnology products.  After a request for information a series of public consultation events started with an October meeting in Washington, D.C.  It marks the first major update to the process since 1992.  It is the first of three public sessions planned.

Earlier this week the dates and locations for the other two sessions were announced.  One will take place on March 9 at the Environmental Protection Agency’s (EPA) Region 6 office in Dallas, and the other will take place on March 30 at the University of California in Davis.  The specific details for how to participate will be available in the Federal Register soon, but I suspect that the process used at the October 2015 meeting will be instructive.  You will likely have the opportunity to submit comments for up to two weeks following the meeting, whether or not you can attend.

Part of the process involves how best to clarify the roles and responsibilities of the EPA, the Food and Drug Administration (FDA), and the Department of Agriculture (USDA) in the regulation of biotechnology products.  While this is a bit of an oversimplification, at present the EPA is involved with regulating these products as they relate to pesticides and applications of microbial technology.  The USDA is interested in these regulations from the perspective of impacts on plant and animal health, and the FDA is concerned with genetically engineered foods, animals and other products under its domain derived from genetically engineered sources.

Following the three meetings and the associated public comment periods, the agencies will work on an update of their common regulatory framework.  That update will also be subject to public review and comment.  The timeframes for each of these steps will eventually be published in the Federal Register, most likely by the Office of Science and Technology Policy.

FTC Takes Aim At “Brain Training”

On Tuesday the Federal Trade Commission announced a settlement with Lumos Labs, the company behind the Luminosity ‘brain training’ subscription program (H/T ScienceInsider).  The company will pay $2 million to its subscribers in connection with its claims that the products would help prevent cognitive decline, reduce cognitive impairment and improve cognitive functioning.  The FTC alleged in its complaint that the company failed to back up its claims and that it failed to disclose that some of the testimonials the company used were solicited with prizes.

The proposed order would require the company to have competent and reliable scientific evidence at hand when making the kinds of claims it did.  Additionally, the company must notify its subscribers that participate in auto-enrollment and allow them means to cancel their subscriptions.

Meanwhile, if you see any advertisements for Luminosity or similar programs, I’d encourage you to ask for evidence behind any claims.