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Tuesday, June 11, 2019

PFAS in food, and findings from recent FDA surveys

Statement From:
Acting
Commissioner of Food and Drugs – Food and Drug Administration
Norman E. “Ned” Sharpless MD
Deputy Commissioner for Food Policy and Response – Food and Drug Administration
Frank Yiannas
At the U.S. Food and Drug Administration, increasing our scientific knowledge and capabilities is a cornerstone to ensuring the safety of the foods that Americans consume. We do this by reviewing all available scientific evidence to determine the safety of foods and food packaging and conducting our own research to fill in gaps in the science. As part of these efforts, the FDA has been working to develop new methods to quantify certain per- and polyfluoroalkyl substances (PFAS) in foods. We have employed these new methods to test samples of foods Americans typically consume for certain types of PFAS, and today we are making available recently analyzed data from these initial testing initiatives.
Overall, our findings did not detect PFAS in the vast majority of the foods tested. In addition, based on the best available current science, the FDA does not have any indication that these substances are a human health concern, in other words a food safety risk in human food, at the levels found in this limited sampling. These data give our scientists a benchmark to use as we continue our critical work studying this emerging area of science.
Background on PFAS
PFAS are a family of human-made chemicals that are found in a wide range of products used by consumers and industry. There are nearly 5,000 types of PFAS, some of which have been more widely used and studied than others. Many PFAS are impermeable to grease, water and oil. For this reason, beginning in the 1940s, PFAS have been used for many different applications including in stain- and water-resistant fabrics and carpeting, cleaning products, paints and fire-fighting foams, as well as in limited, authorized uses in cookware and food packaging and processing, referred to as food contact substances.
The widespread use of PFAS and their ability to remain intact in the environment means that over time PFAS levels from past and current uses can result in increasing levels of contamination of groundwater and soil. This same accumulation also can occur in humans and animals, with PFAS found in the blood of humans and animals worldwide. While the science surrounding the potential health effects of PFAS is developing, current evidence suggests that the bioaccumulation of certain PFAS may cause serious health conditions. However, with the decrease in production and use of certain PFAS, levels in humans in the U.S. have been declining.
PFAS can occur in food through environmental contamination, including contaminated water and soil used to grow the food. This type of contamination can occur in a specific geographic area; for example, a water well or farm near an industrial facility where PFAS were produced, or an oil refinery, airfield, or other location at which PFAS were used for firefighting. PFAS can also come into contact with food as a result of the limited authorized uses as food contact substances.
FDA Testing
Addressing potential effects of Americans’ PFAS exposure is a national priority and effort and work is underway in this area by several government agencies. The U.S. Environmental Protection Agency, the U.S. Department of Agriculture, the National Institutes of Health, and the Centers for Disease Control and Prevention are advancing knowledge around environmental exposures and potential health risks from PFAS, and the Agency is working on issues related to PFAS contamination with these and other federal partners, including the Department of Defense. State health partners are also investigating exposure and working to reduce exposure in local communities. The FDA recognizes its important role in generating, applying and evaluating the science that is needed to begin to estimate exposures from food. As we continue this research, we will be better able to detect, evaluate, and respond more quickly to potential contamination issues involving food.
The FDA has tested foods for PFAS coming from specific geographic areas with known environmental contamination. Recent limited surveys were conducted on dairy products from certain farms in New Mexico and produce from North Carolina, both of which were from specific areas with known PFAS contamination. For every sample for which PFAS was detected, a safety assessment was performed by FDA scientists. In the case of one dairy farm in New Mexico, milk samples were determined to be a potential health concern and all milk from the farm was discarded and not distributed into the American food supply, and milk production from those cattle has been suspended. The Agency continues to work closely with our regulatory partners in the New Mexico Department of Agriculture on these issues. In the case of the produce samples from North Carolina, the levels of PFAS detected were low and, based on our safety assessment using the best available science, samples were determined not likely to be a health concern at the levels found through testing.
To conduct these safety assessments, the FDA reviews relevant information, such as the levels of PFAS found in that food, consumption of that food and the most current toxicological information for PFAS, which we use to determine whether the levels of PFAS found in that food may pose a health concern, especially to vulnerable populations.
Over the last year, we have expanded our testing to analyze for PFAS in foods typically eaten by Americans, and not associated with specific contamination areas. The samples analyzed were from foods originally collected as part of the FDA’s Total Diet Study (TDS) in 2017 and analyzed in 2019. This is the first time the FDA has tested for PFAS in such a highly diverse sample of foods. While no PFAS compounds were detected in the majority of the foods sampled, varying levels of PFAS were found in 14 samples out of 91, but our safety assessment determined the products were not likely to be health concern at the levels that were detected. We plan to continue this testing and currently have new TDS samples in the lab for analysis. Combined with our other sampling, the testing will help us calculate the risks of exposure through food.
Next Steps
Our findings on dairy, produce, and the samples from the TDS were recently presented by FDA scientists at this year’s annual meeting of the Society of Environmental Toxicology and Chemistry (SETAC) in Helsinki, Finland. The purpose of this scientific presentation was to share, with the scientific community, the new methodologies being advanced by the FDA for measuring concentrations of these substances across a wide variety of foods, and the early findings generated from the application of these methods. The FDA has published information on PFAS testing in other foods in the past, but FDA scientists also shared information on its recent limited PFAS testing.
Since PFAS contamination is not specific to the U.S., sharing the FDA’s knowledge and analytical advances with scientists from across the world working on this issue is an important part of our work to begin to address this problem globally. Overall, the FDA’s testing to date has shown that very few foods contain detectable levels of PFAS. However, we know that levels may not be uniform and there is more work to be done. To ensure we are taking the best approach to this complex issue, we have established an internal agency PFAS workgroup with representatives from the human and animal foods programs. A key objective of this workgroup is to establish base-line levels for PFAS in foods, which requires data from these initial and future surveys, and will be used to then estimate overall PFAS exposure. The workgroup will use a systematic, risk-based approach to identify and prioritize FDA activities to reduce exposure to PFAS in human and animal food, guided by available data.
Measuring PFAS concentrations in food, estimating dietary exposure and determining the associated health effects is an emerging area of science. Although the FDA’s scientists are at the forefront of developing new and more sensitive testing methods to measure PFAS in foods, this work does not occur in isolation. We’re also working closely with our federal and state partners to advance the science of PFAS detection and better understand the potential health risks associated with PFAS exposure.
As the FDA continues to evaluate the food supply, we are committed to using the advanced analytical capabilities of FDA labs to generate and share new scientific information, such as our testing methodologies. By working closely with our state partners and helping them to develop their own testing capacities, we can work together to increase the baseline knowledge of PFAS occurrence in foods. We will also continue to support response to local requests about known or possible contamination events.
Federal and state partners each have important roles to play to better understand PFAS exposures and potential health effects, and the FDA will continue to work with these partners to help inform appropriate next steps to protect and promote public health. As part of an era of smarter food safety, the FDA is committed to testing more foods, collaborating with other federal agencies, helping states develop their own testing capacities, and continuing to support responses to contamination events. It is critical that we continue to share our knowledge and leverage existing and new resources as local, state and federal agencies work together to study this emerging public health issue.
We remain committed to sharing further updates as our ongoing surveillance work into PFAS exposure in foods continues.

FDA Issues Guidelines for E-Cig Makers Seeking Approval Of Vape Devices

The Food and Drug Administration released new guidelines Tuesday for manufacturers seeking approval to continue selling e-cigarettes, or vaping devices, and the liquids used in the devices to deliver nicotine.

What Happened

Under FDA regulation of e-cigarettes that began in 2016, e-cigarettes, known by the agency as electronic nicotine delivery systems, or ENDS, that were already on the market had to apply for FDA approval to remain available after August 2021.
As part of the process, manufacturers must submit a “Premarket Tobacco Product Application” in which they have to show the product is “appropriate for the protection of public health.”
The guidelines released Tuesday give companies an idea of what they must do to stay on the market. So far, no e-cigarettes have reached the end of the process.

What It Means

“The final guidance issued today provides companies seeking to market e-cigarette and ENDS products with recommendations to consider as they prepare a premarket tobacco product application to help the FDA evaluate the public health benefits and harms of a product,” Acting FDA Commissioner Ned Sharpless said in a statement.
“There are no authorized e-cigarettes currently on the market.”
Federal officials were caught off guard by research showing growing youth use of e-cigarettes last year and have made reducing the figure a major focus.

The E-Cig Market

Juul has about 75 percent of the U.S. e-cigarette market, according to Nielsen data cited by The Financial Times. U.S. cigarette maker Altria Group IncMO 2.03% has a 35-percent stake in Juul.
British American Tobacco PLC BTI 1.32% makes the second-largest e-cigarette brand, Vuse.
Philip Morris International IncPM 1.56% received approval through the premarket application process April 30 to sell an electronic device that heats tobacco without burning it to produce a nicotine-infused aerosol. That device, iQOS, is already sold in several countries.

Merck’s Keytruda, passing Opdivo, bags double head and neck cancer OK

Tuesday was a twofer for Merck & Co., which notched two new FDA approvals for blockbuster Keytruda in previously untreated head and neck cancer patients.
Regulators green-lighted the immuno-oncology star as monotherapy in patients whose tumors bear the biomarker PD-L1 and in combination with a commonly used chemo regimen in patients regardless of PD-L1 status.
The regulatory wins follow a quick review from the agency, which bestowed its priority designation on Keytruda back in February.
FDA staffers based the speed-up on data showing that that, when facing off against a standard-of-care regimen commonly referred to by the name “Extreme,” Keytruda could lower the risk of death by 22% in PD-L1 positive patients. And when paired with chemo, Keytruda slashed the risk of death by 23% regardless of patients’ PD-L1 status.
With the OKs, Keytruda becomes the first in its class of PD-1/PD-L1 drugs into the first-line head and neck cancer market. The go-ahead unlocks potential use in more than 65,000 patients diagnosed each year in the U.S., Merck said.
It also puts Keytruda ahead of archrival Opdivo from Bristol-Myers Squibb, which is cleared only for patients who have already failed on chemo—meaning those who start out on Keytruda instead of chemo won’t be eligible for Opdivo treatment later.

And the last thing Bristol-Myers needs is to trail Keytruda in another therapy area. It’s already ceded the lead in lung cancer, immuno-oncology’s most lucrative market—and Keytruda has run away with it. And in kidney cancer, an area that’s been historically important to Opdivo sales, Merck recently arrived on the scene with a competing combo approval.

$285M counter-marketing cost to correct opioid misinformation: Expert witness

Countless lawsuits have sought to estimate the costs of fixing the U.S. opioid and addiction epidemic. Now, thanks to an expert in Oklahoma’s ongoing trial against Johnson & Johnson, we have one dollar figure.
Oklahoma would have to spend nearly $285 million to mount a counter-marketing campaign that would offset pharma’s influence over pain prescribing, Saxum Strategic Communications chairman and CEO Renzi Stone testified during the state’s trial against Johnson & Johnson on Monday.
And that’s just the cost of a campaign to spread awareness about the harms of opioids, Stone pointed out in testimony reported by the Oklahoman. It doesn’t include the other costs of fixing the state’s opioid crisis.
“Frankly, I am blown away and impressed,” Stone said of J&J’s opioid marketing at the trial, according to testimony posted by the newspaper. “The marketing materials, the depth of research, the significance of stakeholder mapping, the creation of budgets, the size of budgets, the quarterly review is breathtaking.”
Stone said he was “very surprised” about a lack of training on potential abuse in the J&J materials he reviewed for the trial.
On cross-examination by J&J’s attorney Larry Ottaway, Stone admitted his marketing plan wouldn’t require J&J to stop doing anything.
Ottaway also pressed Stone on opioid prescribing decisions. Who should decide how best to treat patients—the state or the physician? Stone responded that it’s “certainly not the sales and marketing team.”
Stone’s testimony came on day 10 of the state’s trial against J&J. Oklahoma sued the company—plus Teva Pharmaceutical and Purdue Pharma—in 2017, but the other drugmakers settled ahead of trial. Purdue and its founding family agreed to fork over $270 million, and Teva settled for $85 million in an agreement that’s still pending court approval.
Oklahoma alleged opioid makers “manipulated” residents into believing their pain drugs were safe to use for long periods of time. Prosecutors aim to recoup “catastrophic” damages the state has suffered as misleading marketing fueled the opioid addiction crisis.
It remains to be seen just how the nationwide opioid litigation will play out, but Oklahoma is certainly an early test for the industry. And it’s a test that pushed two out of three defendants into a settlement as thousands of other lawsuits are pending. J&J has opted not to settle and argues it marketed opioid painkillers responsibly.

Russia Scientist Wants to Use CRISPR to Modify Babies Despite Call for Global Ban

In November, a Chinese researcher, He Jiankui, used CRISPR-Cas9 gene editing to alter the DNA of embryos for seven couples. The announcement was met by widespread condemnation, investigations and the call for a global moratorium against such research.
Now, Russian molecular biologist Denis Rebrikov told the journal Nature he was considering doing the same thing by the end of this year if he gets approval.
Jiankui used CRISPR to modify the CCR5 genes in the embryos of the Chinese couples. The intention, at least according to He, was to make the babies more resistant to HIV infection. In all seven couples, the fathers had controlled HIV infections, and inactivated CCR5 genes appear to provide some protection against infection. From the point of view of medical necessity, there was no need for the procedure, which was only part of the criticism of it.

In Rebrikov’s case, he wants to disable the gene in embryos that will be implanted into mothers who are HIV-positive. This confers a greater risk of HIV infection to the children than having HIV-positive fathers. The procedure would decrease the risk of passing the virus on to the babies and, according to Rebrikov, would have fewer risks and be more ethically justifiable.
Rebrikov is the director of a genome-editing laboratory at the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology in Moscow. He is also a researcher at the Pirogov Russian National Research Medical University, also in Moscow. Rebrikov indicates he has an agreement with an HIV center to recruit HIV-positive women who want to take part in the procedure.
Further complicating the story is that researchers at UC-Berkeley recently published research that suggested—as many feared—disabling the CCR5 gene has unintended side effects. Analyzing 400,000 records in the UK Biobank, they studied the history of children born naturally with the same edits He Jiankui performed. The researchers found that individuals with two mutated copies of the CCR5 gene had a significantly higher death rate between the ages 41 and 78 than people with one or no copies. They also had a four-fold increased risk of dying from the flu. That research was published in the journal Nature Medicine.
Many countries prohibit the implantation of gene-edited embryos. Russia, for example, has a law that bans genetic engineering in most situations. However, as Nature reports, it’s not clear whether or how the ban would be enforced when it comes to gene editing in an embryo. The Russian laws don’t specifically refer to gene editing. Nature also points out that the China law is ambiguous as well.
Rebrikov indicates he plans to ask for approval from three government agencies, including Russia’s health ministry. He told Nature that could take anywhere from one month to two years.

Jennifer Doudna, one of the discoverers of CRISPR and a molecular biologist at the University of California-Berkeley, told Nature, “The technology is not ready. It is not surprising, but it is very disappointing and unsettling.”
Konstantin Severinov, a molecular geneticist who splits his time between Rutgers University and the Skolkovo Institute of Science and Technology near Moscow, recently assisted the Russian government in designing a funding program for gene-editing research. Severinov told Naturethat getting the government approvals might be difficult. For example, he cites Russia’s Orthodox church, which opposes gene editing.
Although Rebrikov argues that there is a clear medical need in his situation, most geneticists do not think enough is known about the safety of gene editing to conduct it in embryos, and the value, even in this situation, does not justify the risk. There is also skepticism about Rebrikov’s conclusions about his own techniques, which he published in the Bulletin of the RSMU, of which he is the editor-in-chief.
Rebrikov claims that his technique disables both copies of the CCR5 gene more than half the time. Both Doudna and Gaetan Burgio, of the Australian National University in Canberra, expressed doubts about Rebrikov’s data, particularly on whether there were off-target gene edits.
At least in Rebrikov’s case, he appears willing to be turned down by regulators.

Lilly’s Taltz shows long-term benefit in psoriasis study

Five-year data from a Phase 3 clinical trial evaluating Eli Lilly’s (LLY +0.4%) Taltz (ixekizumab) in patients with moderate-to-severe plaque psoriasis showed a durable treatment benefit. The results are being presented at the World Congress of Dermatology in Milan.
More than 90% of treated patients maintained PASI 75 (75% reduction in Psoriasis Area and Severity Index) for five years while almost half maintained completely clear skin.
The FDA approved Taltz for plaque psoriasis in March 2016 followed by approval in Europe a month later.

AbbVie’s Skyrizi shows durable effect in late-stage psoriasis study

Two-year data from a Phase 3 clinical trial, IMMhance, evaluating AbbVie (ABBV +2.3%) and collaboration partner Boehringer Ingelheim’s SKYRIZI (risankizumab) in adult patients with moderate-to-severe plaque psoriasis showed a sustained treatment benefit. The results are being presented at the World Congress of Dermatology in Milan.
After 94 weeks of continuous therapy, 72 – 73% achieved/maintained clear skin (PASI 100/sPGA 0) compared to 2% who were randomized to withdraw at week 28.
The FDA and EC approved the IL-23 inhibitor in April.