Policy Watch: FDA issues draft guidance on genome-editing safety

FDA issues draft guidance on assessing gene-therapy safety

The US Food and Drug Administration released a draft guidance document on Tuesday with recommendations for using next-generation sequencing (NGS) to evaluate the off-target effects of gene-editing therapies.

The guidance is meant for industry sponsors who are seeking approval to begin clinical trials for these therapies. Gene-editing technologies, such as the CRISPR-Cas9 system, can introduce potentially harmful changes to DNA, such as point mutations, insertions or deletions, or chromosome translocations, when the editor cuts DNA at an unintended location.

There are a variety of NGS technologies, and the guidance suggests tailoring the approach to the off-target changes of concern. For instance, short-read sequencing—a highly accurate approach in which the genome is fragmented into sequences a couple hundred bases in length—should be used to detect changes to short stretches of DNA, whereas a long-read sequencing strategy may be best for evaluating the presence of long insertions and deletions.

To assess the off-target editing activity of a given DNA editor, the guidance encourages sequencing a cell type that is identical or similar to the one being edited. If such cell types are difficult to obtain, and other assays for testing safety are unavailable, researchers can consider using computational algorithms to identify regions of the genome similar to the target sequence.

According to the FDA, the draft guidance complements the “plausible mechanism” framework that the agency described in a separate draft guidance in February, by which a single gene-editing product could be approved for multiple gene targets. The framework “revolutionizes how the FDA engages with industry and promotes a path for transformative rare disease treatments,” a Department of Health and Human Services spokesperson tells C&EN.

The American Society of Gene and Cell Therapy, a professional organization for the advancement of gene and cell therapies, did not respond to a request for comment.

—Yaakov Zinberg, special to C&EN

EPA advances 4 overdue TSCA chemicals to draft review

The US Environmental Protection Agency on April 10 released draft reviews of four chemicals under the Toxic Substances Control Act (TSCA). All four are on the list of 20 high-priority chemicals that the agency was due to finish assessing by December 2022.

The agency published draft risk evaluations for phthalic anhydride, an intermediate in plasticizer and resin manufacture, and 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[g]-2-benzopyran (HHCB), a fragrance additive. It also posted draft hazard assessments for o-dichlorobenzene (oDCB) and p-dichlorobenzene (pDCB), both used as solvents and chemical intermediates.

In its preliminary reporting, the EPA found an unreasonable risk to human health for phthalic anhydride in 38 of the 44 evaluated uses. Of these, 36 are a risk to workers. The remaining two uses—in adhesives and sealants, and in paints and coatings—pose a risk to consumers. The agency did not find any unreasonable risks of injury to human health or the environment for HHCB’s evaluated uses. In the draft hazard assessments for oDCB and pDCB, the EPA found serious noncarcinogenic risks to human health, including potential harm to the liver, kidneys, respiratory system, and nervous and reproductive systems.

The draft evaluations for all four chemicals are open for public comment. The EPA will hold a virtual public meeting on May 26 with the Science Advisory Committee on Chemicals (SACC) to discuss the draft charge questions for subsequent peer review meetings. The SACC and the EPA will then hold those peer review meetings online from June 8 to 12 to review each of the drafts.

This comment period will close for oDCB and pDCB on May 29, and for HHCB and phthalic anhydride on June 15.

According to the law firm Beveridge & Diamond, the EPA is under a legally binding agreement to finish 11 risk evaluations by the end of the year. The agency published final scopes for each of the risk evaluations in August 2020 but still hasn’t finished draft risk evaluations for seven of these compounds.

—Leigh Krietsch Boerner

Virginia and Maryland enact laws to manage PFAS-containing sewage sludge

Virginia and Maryland have both recently passed legislation restricting how sewage sludge that contains per- and polyfluoroalkyl substances (PFAS) can be used.

Virginia’s HB1443/SB 386, signed by Governor Abigail Spanberger (D) on April 13, requires owners of sewage treatment plants to get permits before marketing and distributing sewage sludge to farmers or letting it be applied to land. The law also requires treatment plants to test samples of the sewage sludge for PFAS, beginning in January. After July 1, 2027, sludge with perfluorooctanoic acid (PFOA) or perfluorooctane sulfonic acid (PFOS) concentrations above 50 μg/kg cannot be applied to land or otherwise marketed or distributed. The application rate of sludge with PFOA or PFOS between 25 and 50 μg/kg will be limited.

Maryland’s HB925/SB719 would set the same limits on the use of sewage sludge containing PFOA or PFOS but beginning in October 2028, more than a year after Virginia. The legislation has passed both chambers and awaits Governor Wes Moore’s (D) signature.

Local environmental advocates say the Virginia and Maryland bills are an important first step but call for stricter limits.

“States like Maryland and Virginia are stepping up where the federal government has failed—and that matters,” says Betsy Nicholas, president of Potomac Riverkeeper Network, in a written statement. “Requiring testing and disclosure is a critical first step, because you cannot manage what you don’t measure. But we also know that PFAS are harmful at far lower levels than allowed by these laws.”

—Delger Erdenesanaa

Release of NOAA funding spares researchers from furloughs

Funds are flowing again to the National Oceanic and Atmospheric Administration’s Global Monitoring Laboratory (GML), sparing its scientists and administrative staff from a possible furlough. After much delay, the US Office of Management and Budget (OMB) released $4.28 million in federal funding to GML on April 16.

Earlier this month, the University of Colorado Boulder, which employs around half of the researchers at GML through its Cooperative Institute for Research in Environmental Sciences (CIRES), put out a statement saying that even though funding had already been approved, “the US Office of Management and Budget (OMB) has not released these funds.” The delay in funding, the university said, meant that CIRES researchers at GML were at “risk of elimination” and would have been furloughed had funding not arrived by May 15.

Those furlough notices have now been rescinded.

“The release of these funds and the resumption of work at the Global Monitoring Lab is welcome news—not only for the scientists and staff directly affected, but for the broader scientific mission we share as a research university,” says Massimo Ruzzene, senior vice chancellor for research and innovation at CU Boulder, in the updated statement. At GML, CIRES researchers work alongside NOAA scientists to measure stratospheric ozone recovery, track greenhouse gas emissions, and monitor changes in clouds, aerosols, and surface radiation.

NOAA isn’t the only federal agency that has had to deal with funding delays, which are happening even though Congress finalized the budgets for these agencies back in late January and early February. Typically, after Congress appropriates these funds, agencies are allowed to use this money in 30-day increments until the OMB approves their spending plans. But, last August, the OMB updated its guidance to agencies, saying they can use this portion of their funding only to cover essential expenses “that are obligated as a matter of law.”

According to reporting by Nature, it took 3 weeks after the budget for the US National Science Foundation was finalized on Jan. 23 for the OMB to release the agency’s funds. It didn’t release appropriated funds for the National Institutes of Health, finalized on Feb. 3, until nearly 6 weeks later.

NOAA’s budget had been finalized at the same time as the NSF’s.

The OMB did not respond to C&EN’s request for comment in time for publication.

—Krystal Vasquez

EPA delays PFAS reporting, starts water system outreach program

The US Environmental Protection Agency is once again delaying the timeline for companies to report information about per- and polyfluoroalkyl substances (PFAS) they manufactured or imported between 2011 and 2022 as part of a 2023 rule (PDF) under the Toxic Substances Control Act section 8(a)(7).

In November 2025, the EPA proposed changes to the 2023 rule that would exempt imports of many PFAS-containing products from the reporting requirements and received more than 8,000 public comments in response.

The agency is now pushing back the start of the PFAS reporting period to 60 days after the effective date of the forthcoming revision or Jan. 31, 2027, whichever comes sooner. Officials expect to finalize those changes “well before that fallback date,” according to the April 13 Federal Register notice. The revised rule will include the deadline for reporting. The original 2023 rule gave companies 6 months.

Separately, the EPA announced on April 14 that it is beginning to implement its new PFAS OUT program for public drinking-water systems. The agency will reach out this summer to water systems with levels of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) above 4 parts per trillion and connect them with resources to address those substances.

The program’s goal, according to the announcement, is to prepare these water systems to comply with new federal maximum contaminant levels for PFOA and PFOS, which will be enforced beginning in 2029 or 2031. The EPA also plans to host a webinar series later this year that will be open to all water systems.

—Delger Erdenesanaa