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Here's a look at documents from the U.S. Executive Branch
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Smithsonian Craft Show Opens April 23
WASHINGTON, March 25 -- The Smithsonian Institution issued the following news release on March 24, 2026:* * *
Smithsonian Craft Show Opens April 23
Juried Fine Craft Show Celebrates American Artistry
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The 44th annual Smithsonian Craft Show will take place April 22-26 featuring the work of recognized masters and outstanding innovators of American craft. A panel of expert jurors has selected 120 American artists representing all facets of contemporary craft and design, including basketry, ceramics, decorative fiber, furniture, glass, jewelry, leather, metal, mixed-media, paper, wearable art ... Show Full Article WASHINGTON, March 25 -- The Smithsonian Institution issued the following news release on March 24, 2026: * * * Smithsonian Craft Show Opens April 23 Juried Fine Craft Show Celebrates American Artistry * The 44th annual Smithsonian Craft Show will take place April 22-26 featuring the work of recognized masters and outstanding innovators of American craft. A panel of expert jurors has selected 120 American artists representing all facets of contemporary craft and design, including basketry, ceramics, decorative fiber, furniture, glass, jewelry, leather, metal, mixed-media, paper, wearable artand wood. The works will be on display and for sale. Serious collectors and casual shoppers will find one-of-a-kind pieces at a wide range of prices.
The show will be held at the National Building Museum, located at 401 F St. N.W. in Washington, D.C. Admission is $25, and group sales of 10 or more are $20 each, both of which can be purchased in advance or online.
The show's Preview Night Benefit April 22 offers an early opportunity to view and purchase crafts while enjoying cocktails and dinner. Tickets and more information are available on the craft show website.
The 2026 honorary chair is Carol Sauvion, the former executive director of Craft in America, and the guiding force behind Handwork: Celebrating American Craft 2026, a nationwide initiative to showcase 250 years of American craft.
A highlight of the Preview Night Benefit will be the presentation of the Smithsonian Visionary Award to Wayne Higby for his significant achievements in sculptural art and design. Ceramic artist Cristina Cordova will receive the Delphi Award from the Smithsonian Women's Committee for her exceptional mid-career artistry and promise.
The Smithsonian Women's Committee produces this show to celebrate the finest in American contemporary craft and design. All proceeds go back to the Smithsonian through grants to multiple museums, research centers and the Zoo. To date, the organization has awarded more than $15 million to the Institution for projects that support innovative education and enhance knowledge, research and outreach in areas of culture, arts, mysteries of the universe, biodiversity and the American experience.
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About the Smithsonian Women's Committee
The Smithsonian Women's Committee is an all-volunteer organization of 180 members that raises funds through its annual Smithsonian Craft Show and Craft2Wear Show to fund its grants and endowment programs to support the initiatives of the Smithsonian's 21 museums, 21 libraries, the National Zoo and numerous education, research and conservation centers in the Washington, D.C., area and around the world.
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Original text here: https://www.si.edu/newsdesk/releases/smithsonian-craft-show-opens-april-23
Pakistani National Residing in Southern California Charged With Fraudulently Billing Medicare Plans
PORTLAND, Oregon, March 25 -- The office of the U.S. Attorney for the District of Oregon posted the following news release on March 24, 2026:* * *
Pakistani National Residing in Southern California Charged with Fraudulently Billing Medicare Plans
The owner of Oregon Clinical Laboratory in Klamath Falls, Oregon, has been charged by criminal complaint with healthcare fraud after allegedly participating in a scheme to fraudulently bill Medicare Advantage insurance plans for laboratory testing services never performed.
Jahangeer Ali, 34, a citizen of Pakistan, made his first appearance on February ... Show Full Article PORTLAND, Oregon, March 25 -- The office of the U.S. Attorney for the District of Oregon posted the following news release on March 24, 2026: * * * Pakistani National Residing in Southern California Charged with Fraudulently Billing Medicare Plans The owner of Oregon Clinical Laboratory in Klamath Falls, Oregon, has been charged by criminal complaint with healthcare fraud after allegedly participating in a scheme to fraudulently bill Medicare Advantage insurance plans for laboratory testing services never performed. Jahangeer Ali, 34, a citizen of Pakistan, made his first appearance on February27, 2026, in the Central District of California. A detention hearing was held on March 4, 2026, in the Central District of California and Ali was ordered detained pending further court proceedings.
According to court documents, from June 2025 through January 2026, Oregon Clinical Laboratory submitted more than $46 million in fraudulent claims to Medicare Advantage plans. However, no providers actually ordered testing services and none of the Medicare Advantage beneficiaries on the claims actually received testing services from the company. As a result of the fraud, Medicare Advantage plans paid out over $28 million on the fraudulent claims.
On February 26, 2026, Ali was arrested at the Los Angeles International Airport prior to boarding a flight to Turkey with an ultimate destination of Pakistan.
A detention hearing was held today in the District of Oregon and Ali was ordered to remain in custody pending further court proceedings.
The U.S. Department of Health and Human Services, Office of Inspector General and Federal Bureau of Investigation are investigating the case. Assistant U.S. Attorney Andrew T. Ho is prosecuting the case.
A criminal complaint is only an accusation of a crime, and a defendant is presumed innocent unless and until proven guilty.
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Original text here: https://www.justice.gov/usao-or/pr/pakistani-national-residing-southern-california-charged-fraudulently-billing-medicare
NOAA: Studies Will Improve Abundance Estimates for Ice Seals in Alaska
WASHINGTON, March 25 (TNSjou) -- The U.S. Department of Commerce National Oceanic and Atmospheric Administration issued the following news:* * *
New Studies Will Improve Abundance Estimates for Ice Seals in Alaska
March 24, 2026
New research on haul-out behavior helps to more accurately estimate the number of ice seals in the Arctic, and improve our efforts to conserve and monitor their populations.
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NOAA Fisheries scientists recently published two studies on bearded, ribbon, and spotted seal haul-out behavior (https://peerj.com/articles/18160/) and the spring "emergence" of ringed seals ... Show Full Article WASHINGTON, March 25 (TNSjou) -- The U.S. Department of Commerce National Oceanic and Atmospheric Administration issued the following news: * * * New Studies Will Improve Abundance Estimates for Ice Seals in Alaska March 24, 2026 New research on haul-out behavior helps to more accurately estimate the number of ice seals in the Arctic, and improve our efforts to conserve and monitor their populations. * NOAA Fisheries scientists recently published two studies on bearded, ribbon, and spotted seal haul-out behavior (https://peerj.com/articles/18160/) and the spring "emergence" of ringed seals(https://onlinelibrary.wiley.com/doi/10.1002/ece3.72948). This research provides critical information on the percentage of seals hauled out on sea ice to those remaining in the water. It also describes how seal behavior changes with the weather and time of day. This information enables us to account for seals that are not photographed because they are in the water during surveys or hidden in snow-covered dens. As a result, we can use a "correction model" to improve the accuracy of abundance estimates along with efforts to conserve and manage seal populations.
In spring 2025, scientists conducted a large-scale aerial survey of the Bering, Chukchi, and Beaufort seas of Alaska. They photographed and counted the number of ringed, bearded, ribbon, and spotted seals (collectively called "ice seals") hauled out on ice. Ice seals rely heavily on sea ice for resting and nurturing their pups. But, not all seals haul out on the ice at the same time. These new studies allow scientists to produce better overall abundance estimates. They can better estimate how many seals are in the water, and thereby missed by the aerial counts.
Multi-Year Study Provides Important Biological and Behavioral Information
The first study, published in PeerJ, relies on data from electronic devices known as biologgers attached to seals. The results provide insights on when seals are more likely to be hauled out on the ice. They also show how that behavior is impacted by season, time of day, and weather.
"We found that seals are more likely to haul out on ice in the middle of the day and when wind speed is low and temperatures are higher," said Josh London, lead author of the paper and marine mammal biologist at the Alaska Fisheries Science Center. "Haul-out behavior increased through March and April, peaking in May and early June before declining again."
This season matches the period during which seals are nursing their pups, breeding, and molting, when they benefit from more time out of the water. The specific timing and frequency of haul-out behavior also differs across age and sex.
"Before the study, these daily and monthly patterns were generally understood, but the biologgers allowed us to precisely quantify them for the first time," said London.
The biologgers in the study rely on special sensors that measure conductivity. Because saltwater is more conductive than air, they can determine whether the device--and therefore the seal--is in or out of the water. When on the surface, the device transmits the seal's haul-out behavior data to researchers through the Argos satellite network. Satellite transmission is essential for the research given the extremely remote location.
We have deployed biologgers on seals in several studies that have spanned 15 years. We partnered with the Alaska Department of Fish and Game and the North Slope Borough Wildlife Management. We also worked in close collaboration with Alaska Native community members.
For this study, researchers used two types of biologgers. The first type is glued to the seal's hair and provides location and behavioral (e.g., diving and hauling out) information via satellite until it falls off. These devices usually fall off during the molt, which also happens during our study period. We attach a second biologger device to the webbing of the seal's rear flipper. Biologgers attached to the flipper are much smaller with batteries that can last 1-2 years. Importantly, they stay attached to the seal during the molt period. These deployments provide location information when the seal is out of the water and can transmit up to several months of data indicating the portion of each hour the tag was out of the water.
Ice Seal Study Findings
Ice-associated seals rely on sea ice for pupping, breeding, molting, and resting. In the Arctic, many of these activities occur in spring (April through June) as sea ice begins to melt and the edge of the pack recedes northward. Warming of Arctic ecosystems could decrease the quantity and quality of suitable habitat. Robust estimates of seal population abundances are needed to properly monitor the impacts of these changes over time.
Results from the study also provide a clearer picture of how reliant these seal species are on sea ice in the Bering Sea during the spring months. Sub-adult ribbon seals start increasing their time hauled out on the ice in early April, followed by adult females who are about to give birth at that time. Adult males increase their use of the ice a short time later, in early to mid-May. In the early part of the spring, haul-out behavior is centered around solar noon--when the sun is at its highest point in the sky. As the season progresses, though, seals use the ice throughout the day. During their molt, seals shed their hair and grow an entirely new coat. This requires a lot of energy, and the seals benefit from extended hours resting, out of the water and in the warmer sun.
A Hidden Challenge: Ringed Seals in Snow Lairs
Ringed seals present a unique challenge. They build snow-covered dens ("lairs") on the sea ice. This means a ringed seal can be out of the water, but still remain hidden from aerial surveys.
Lairs provide a warm, dry place for ringed seals to rest during the winter and to have their pups in March and April. Later in the spring, ringed seals switch from using lairs to basking on the surface of the ice, a transition called "emergence." Understanding the timing of this behavioral switch is important for estimating what fraction of the seal population is visible to aircraft.
The second study, published in Ecology and Evolution, focuses on this puzzle. Researchers also used biologger data to estimate when emergence occurs. "We found that adult ringed seals typically emerged in mid-May, and that the likelihood of emergence increased substantially with warmer temperatures and longer days," said Jessica Lindsay, lead author of the paper and biologist at the Alaska Fisheries Science Center. After emergence, ringed seals spent more time out of the water and centered their haul-out behavior around solar noon. Authors on this study included NOAA scientists and co-authors from:
* Alaska Department of Fish and Game
* North Slope Borough Department of Wildlife Management
* University of Washington
The study also revealed that timing varies by latitude; seals farther north in the Beaufort Sea emerge later than those in the Bering Sea. Understanding when this transition happens geographically will help scientists time their surveys to get the most accurate counts in the different regions.
Benefit to Future Survey Efforts
Scientists will integrate information from these studies with data collected during aerial surveys to predict what portion of the seal population is on the ice and available to count. Together, these pieces of information allow researchers to estimate current abundances of bearded, ribbon, spotted, and ringed seals in Alaska. Accurate abundance estimates are essential for conservation of these species and co-management with Alaska Native communities. Over time, researchers will also be able to better monitor how these populations are responding to environmental changes in the ecosystem.
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Original text here: https://www.fisheries.noaa.gov/feature-story/new-studies-will-improve-abundance-estimates-ice-seals-alaska
FEMA Provides More Than $6.7 Million in Funding to Support Disaster Survivors in New Mexico, Oklahoma and Texas
WASHINGTON, March 25 -- The U.S. Department of Homeland Security Federal Emergency Management Agency issued the following news release:* * *
FEMA Provides More Than $6.7 Million in Funding to Support Disaster Survivors in New Mexico, Oklahoma and Texas
DENTON, Texas - FEMA has approved more than $6.7 million in funding to support state-managed recovery programs as a result of multiple disasters declared in 2024 and 2025. These funds directly support individuals, families and communities in FEMA Region 6 by addressing some of their most urgent needs after a disaster.
More than $963,000 was ... Show Full Article WASHINGTON, March 25 -- The U.S. Department of Homeland Security Federal Emergency Management Agency issued the following news release: * * * FEMA Provides More Than $6.7 Million in Funding to Support Disaster Survivors in New Mexico, Oklahoma and Texas DENTON, Texas - FEMA has approved more than $6.7 million in funding to support state-managed recovery programs as a result of multiple disasters declared in 2024 and 2025. These funds directly support individuals, families and communities in FEMA Region 6 by addressing some of their most urgent needs after a disaster. More than $963,000 wasawarded for Disaster Unemployment Assistance to the states of New Mexico and Texas. This assistance may help people who are not able to work as a direct result of the disaster. This assistance is funded by FEMA and administered by the states in partnership with the New Mexico Department of Homeland Security and Emergency Management and the Texas Division of Emergency Management.
Another $5.8 million was awarded to the states of New Mexico and Oklahoma to help people develop a long-term recovery plan and coordinate support with a case manager through FEMA's Disaster Case Management program. A case manager empowers households to return to a state of independence.
The six disasters receiving funding are:
* New Mexico South Fork Fire and Salt Fire; declaration date: June 20, 2024 (DR-4795-NM)
* New Mexico Severe Storms, Flooding, and Landslides; declaration date: July 22, 2025 (DR-4886-NM)
* Oklahoma Severe Storms, Straight-line Winds, Tornadoes, and Flooding; declaration date: April 30, 2024 (DR-4776-OK)
* Oklahoma Severe Storms, Straight-line Winds, Tornadoes, and Flooding; declaration date: June 14, 2024 (DR-4791-OK)
* Texas Severe Storms, Straight-line Winds, Tornadoes, and Flooding; declaration date: May 17, 2024 (DR-4781-TX)
* Texas Hurricane Beryl; declaration date: July 9, 2024 (DR-4798-TX)
FEMA will continue to work closely with New Mexico, Oklahoma and Texas to support individuals and communities throughout the state-led recovery efforts.
For more information on FEMA-funded, state-managed recovery programs, visit fema.gov/assistance/individual/disaster-survivors.
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About FEMA Region 6
The FEMA Region 6 office, located in Denton, Texas, partners with 68 Tribal Nations and the states of Arkansas, Louisiana, New Mexico, Oklahoma and Texas. Follow us at x.com/FEMARegion6 and at linkedin.com/showcase/fema-region-6/ and like us at facebook.com/FEMARegion6/
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Original text here: https://www.fema.gov/about/news-multimedia/press-releases
FDA Center for Tobacco Products Issues Warning Letter to Matesbrand.com
WASHINGTON, March 25 -- The U.S. Department of Health and Human Services Food and Drug Administration issued the following warning letter to matesbrand.com from its Center for Tobacco Products:* * *
Recipient: matesbrand.com, United States, hi@matesbrand.com
Issuing Office: Center for Tobacco Products, United States
WARNING LETTER
To Whom It May Concern:
The Center for Tobacco Products of the U.S. Food and Drug Administration (FDA) recently reviewed the website https://www.matesbrand.com and determined that nicotine pouch products listed there are offered for sale or distribution to customers ... Show Full Article WASHINGTON, March 25 -- The U.S. Department of Health and Human Services Food and Drug Administration issued the following warning letter to matesbrand.com from its Center for Tobacco Products: * * * Recipient: matesbrand.com, United States, hi@matesbrand.com Issuing Office: Center for Tobacco Products, United States WARNING LETTER To Whom It May Concern: The Center for Tobacco Products of the U.S. Food and Drug Administration (FDA) recently reviewed the website https://www.matesbrand.com and determined that nicotine pouch products listed there are offered for sale or distribution to customersin the United States.
Under section 201(rr) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. Sec. 321(rr)), these products are tobacco products because they are made or derived from tobacco or contain nicotine from any source and intended for human consumption. Certain tobacco products, including nicotine pouch products, are subject to FDA jurisdiction under section 901(b) of the FD&C Act (21 U.S.C. Sec. 387a(b)) and 21 C.F.R. Sec. 1100.1 and are required to be in compliance with the requirements in the FD&C Act.
Generally, to be legally marketed in the United States, the FD&C Act requires "new tobacco products" to have a premarket authorization order in effect. A "new tobacco product" is any tobacco product that was not commercially marketed in the United States as of February 15, 2007, or any modified tobacco product that was commercially marketed after February 15, 2007 (section 910(a) of the FD&C Act; 21 U.S.C. Sec. 387j(a)). Generally, a marketing authorization order under section 910(c)(1)(A)(i) of the FD&C Act (21 U.S.C. Sec. 387j(c)(1)(A)(i)) is required for a new tobacco product unless (1) the manufacturer of the product submitted a report under section 905(j) of the FD&C Act (21 U.S.C. Sec. 387e(j)) and FDA issues an order finding the product substantially equivalent to a predicate tobacco product (section 910(a)(2)(A) of the FD&C Act) or (2) the manufacturer submitted a report under section 905(j)(1)(A)(ii) of the FD&C Act (21 U.S.C. Sec. 387e(j)(1)(A)(ii)) and all modifications are covered by exemptions from the requirements of substantial equivalence granted by FDA under section 905(j)(3) of the FD&C Act (21 U.S.C. Sec. 387e(j)(3)).
New Tobacco Products Without Required Marketing Authorization Are Adulterated and Misbranded
FDA has determined that you offer for sale or distribution to customers in the United States nicotine pouch products that lack a marketing authorization order, including: Pouchmates Nicotine Pouches - Peach Smoothie and Pouchmates Nicotine Pouches - Strawberry Raspberry.
The tobacco products listed above are new tobacco products because they were not commercially marketed in the United States as of February 15, 2007. These products do not have FDA marketing authorization orders in effect under section 910(c)(1)(A)(i) of the FD&C Act and are not otherwise exempt from the marketing authorization requirement. Therefore, these products are adulterated under section 902(6)(A) of the FD&C Act (21 U.S.C. Sec. 387b(6)(A)). In addition, they are misbranded under section 903(a)(6) of the FD&C Act (21 U.S.C. Sec. 387c(a)(6)) because a notice or other information respecting these products was not provided as required by section 905(j) of the FD&C Act (21 U.S.C. Sec. 387e(j)).
Conclusion and Requested Actions
FDA has determined that your firm markets new tobacco products in the United States that lack premarket authorization. All new tobacco products on the market without the statutorily required premarket authorization are marketed unlawfully and are subject to enforcement action at FDA's discretion.
For a list of all products that have been authorized by the FDA and certain others that may be legally marketed, please visit the Searchable Tobacco Products Database: https://www.fda.gov/searchtobacco.
It is your responsibility to ensure that all tobacco products you sell and/or distribute in the United States and all related labeling and/or advertising on any websites or other media (such as e-commerce, social networking, or search engine websites), and in any retail establishments in which you advertise, comply with each applicable provision of the FD&C Act and FDA's implementing regulations. Failure to address any violations of the FD&C Act, 21 U.S.C. Sec. 301 et seq., or its implementing regulations relating to tobacco products including the tobacco regulations in 21 C.F.R. Parts 1140, 1141, and 1143, may lead to regulatory action, including, but not limited to, civil money penalties, seizure, and/or injunction. However, this Warning Letter does not constitute "written notice" for purposes of section 303(f)(9)(B)(i)(II) of the FD&C Act. Please note that tobacco products offered for import into the United States that appear to be adulterated and/or misbranded may be detained or refused admission.
The violations discussed in this letter do not necessarily constitute an exhaustive list. You should take prompt action to address any violations that are referenced above, as well as violations that are the same as or similar to the ones stated above, and take any necessary actions to bring these tobacco products into compliance with the FD&C Act.
Please submit a written response to this letter within 15 working days from the date of receipt describing your actions to address any violations and bring these products into compliance, including the dates on which you discontinued the violative sale and/or distribution of these tobacco products and your plan for maintaining compliance with the FD&C Act. If you believe that these products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration. This letter notifies you of our findings and provides you with an opportunity to address them. You can find the FD&C Act through links on FDA's homepage at https://www.fda.gov.
Please note your reference number, RW2602398, in your response and direct your response via email at CTPCompliance@fda.hhs.gov and to the following address:
DPAL-WL Response, Office of Compliance and Enforcement
FDA Center for Tobacco Products
c/o Document Control Center
Building 71, Room G335
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
If you have any questions about the content of this letter, please contact CTPCompliance@fda.hhs.gov.
Sincerely,
/S/ John E. Verbeten, Director, Office of Compliance and Enforcement, Center for Tobacco Products
VIA UPS and Electronic Mail
cc:
7D Holdings, LLC
7 Daze LLC
Attn: John Lau
1425 South Vineyard Avenue
Ontario, CA 91761
* * *
7D Holdings, LLC
8 The Green, Suite R
Dover, DE 19901
* * *
7 Daze LLC
Attn: John Lau
13170 Spring Street
Baldwin Park, CA 91706
info@7dazemfg.com
* * *
GoDaddy.com, LLC
abuse@godaddy.com
* * *
Shopify, Inc.
abuse@shopify.com
* * *
Original text here: https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/matesbrandcom-725802-03202026
FDA Center for Devices & Radiological Health Issues Warning Letter to Longhorn Vaccines & Diagnostics
WASHINGTON, March 25 -- The U.S. Department of Health and Human Services Food and Drug Administration issued the following warning letter to Longhorn Vaccines and Diagnostics LLC from its Center for Devices and Radiological Health:* * *
Recipient: Jeffrey D. Fischer, President, Longhorn Vaccines and Diagnostics LLC, 7272 Wisconsin Avenue, Ste 900, Bethesda, MD 20814, United States, jeff@lhnvd.com
Issuing Office: Center for Devices and Radiological Health, United States
WARNING LETTER
CMS # 721702
Dear Mr. Jeffrey D. Fischer:
During an inspection of your firm located in Bethesda, MD from ... Show Full Article WASHINGTON, March 25 -- The U.S. Department of Health and Human Services Food and Drug Administration issued the following warning letter to Longhorn Vaccines and Diagnostics LLC from its Center for Devices and Radiological Health: * * * Recipient: Jeffrey D. Fischer, President, Longhorn Vaccines and Diagnostics LLC, 7272 Wisconsin Avenue, Ste 900, Bethesda, MD 20814, United States, jeff@lhnvd.com Issuing Office: Center for Devices and Radiological Health, United States WARNING LETTER CMS # 721702 Dear Mr. Jeffrey D. Fischer: During an inspection of your firm located in Bethesda, MD fromOctober 20, 2025 through October 30, 2025, investigators from the United States Food and Drug Administration (FDA) determined that your firm is a specification developer of the PrimeStore(R) MTM (Molecular Transport Medium) device intended for the stabilization, transportation, and inactivation of infectious unprocessed nasal washes suspected of containing Influenza A virus RNA as well as unprocessed sputum samples suspected of containing Mycobacterium tuberculosis DNA from human samples. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. Sec. 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body.
Quality System Regulation Violations
This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. Sec. 351(h), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the current good manufacturing practice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820. These violations include, but are not limited to, the following:
1. Failure to maintain complaint files and establish and maintain procedures for receiving,reviewing, and evaluating complaints by a formally designated unit to ensure that allcomplaints are processed in a uniform and timely manner; oral complaints are documentedupon receipt; and complaints are evaluated to determine whether the complaint represents anevent which is required to be reported to FDA under part 803 of this chapter, Medical DeviceReporting, as required by 21 CFR 820.198(a) and 21 CFR 820.198(a)(1) through820.198(a)(3).
Specifically:
A. Complaints files are not adequately maintained, as required by 21 CFR 820.198(a). For example, alleged deficiencies of your PrimeStore(R) MTM devices received via thirteen (13) emails between 2020 and 2022 were not documented in controlled records.
B. Your firm did not have a procedure for complaint handling (QSP-COM-001; Rev. 1.0; Effective: 10/27/25), until during the inspection. This procedure lacks requirements for:
1) Uniform and timely processing of complaints, as required by 21 CFR 820.198(a)(1);
2) Documentation of oral complaints upon receipt, as required by 21 CFR 820.198(a)(2); and
3) Evaluation of complaints to determine whether the complaint represents an event which is required to be reported to FDA under 21 CFR 803 (Medical Device Reporting), as required by 21 CFR 820.198(a)(3). For example, your firm failed to evaluate complaints for medical device reportability received for your PrimeStore(R) MTM devices regarding leakage of "(b)(4)" between 2020 and 2022; two (2) incidents of ingestion in 2022; two (2) incidents of skin exposure in 2021; and FDA notification of cyanide release in 2020 due to usage on incompatible systems consisting of a bleach step (RES 86189).
2. Failure to review and evaluate all complaints to determine whether an investigation is necessary. When no investigation is made, the manufacturer shall maintain a record that includes the reason no investigation was made and the name of the individual responsible for the decision not to investigate, as required by 21 CFR 820.198(b).
For example, your firm did not review and evaluate whether the two (2) complaints of ingestion in 2022 and two (2) complaints of skin exposure in 2021 required investigations or document reasons for why no investigations were necessary.
3. Failure to investigate any complaint involving the possible failure of a device, labeling or packaging to meet any of its specifications, unless such investigation has already been performed for a similar complaint and another investigation is not necessary, as required by 21 CFR 820.198(c).
Specifically, your firm does not have any documented investigations for the following complaints which involve the possible failure of your PrimeStore(R) MTM device, labeling, or packaging to meet any of its specifications:
* Leakage of "(b)(4)" between 2020 and 2022;
* Release of cyanide after usage of device on incompatible systems (RES 86189)
4. Failure to establish and maintain procedures for implementing corrective and preventive action, including requirements for analyzing processes, work operations, concessions, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential causes of nonconforming product, or other quality problems using appropriate statistical methodology; investigating the cause of nonconformities relating to product, processes, and the quality system; identifying the action(s) needed to correct and prevent recurrence of nonconforming product and other quality problems; and verifying or validating the corrective and preventive action to ensure that such action is effective and does not adversely affect the finished device, as required by 21 CFR 820.100(a) and 21 CFR 820.100(a)(1) through 820.100(a)(4).
Specifically:
A. Your firm did not have a procedure for implementing corrective and preventive action (CAPA) (QSP-CAPA-001; Rev. 1.0; Effective: 10/27/25), until during this inspection, as required by 21 CFR 820.100(a).
B. Your firm failed to analyze your processes, work operations, complaints, and other sources of quality data to identify existing and potential causes of nonconforming product, or other quality problems, as required by 21 CFR 820.100(a)(1).
C. Your firm failed to investigate the cause and identify actions needed to prevent recurrence along with the verification or validation of the effectiveness of such actions, as required by 21 CFR 820.100(a)(2) through 21 CFR 820.100(a)(4), for the following known, systemic issues:
* Field correction RES 86189 initiated on June 3, 2020 urging users to apply labels to the (b)(4) PrimeStore(R) MTM devices which had been distributed without a label and avoid contact with bleach to prevent the release of cyanide gas.
* Complaints received for leakage of "(b)(4)" between 2020 and 2022.
5. Failure to establish and maintain procedures to control the design of the device in order to ensure that specified design requirements are met to demonstrate that the design was developed in accordance with the design control requirements, as required by 21 CFR 820.30(a) through 820.30(j).
Specifically:
A. Your firm did not have procedures to control the design of your PrimeStore(R) MTM devices ("PrimeStore(R) MTM - Design Control Document" created October 18, 2025), until during this inspection, as required by 21 CFR 820.30(a).
B. Your firm did not have a design and development plan in place for your PrimeStore(R) MTM devices ("Design and Development***" section of "PrimeStore(R) MTM - Design History File (DHF)" [Rev. 1.0; Effective: 10/21/25]), until during this inspection, as required by 21 CFR 820.30(b). Although the "Design and Development Plan" section of this document contains a historical summary of product development, it fails to define responsibility for implementation and identify and describe the interfaces with different groups or activities that provide, or result in, input to the design and development process.
C. Your firm did not have a design input procedure ("Design Inputs***" section of "PrimeStore(R) MTM - Design Control Document" created October 18, 2025 which was superseded by "Design Input Procedure***" [SOP-DV-004; Rev. 1.0; Effective: 10/27/25]), until during this inspection, as required by 21 CFR 820.30(c). Although the design input section of the "PrimeStore(R) MTM - Design Control Document" states "***(b)(4)***," it fails to include a mechanism for addressing incomplete, ambiguous, or conflicting requirements.
For example, the following design inputs, created as a part of the "PrimeStore(R) MTM - Design History File (DHF)" (Rev. 1.0; Effective: 10/21/25) at the time the "PrimeStore(R) MTM - Design Control Document" procedure was in effect, are ambiguous in that they lack or fail to make reference to clearly defined requirements:
* (b)(4)
* (b)(4)
* (b)(4)
* (b)(4)
D. Your firm did not have a design output procedure ("Design Outputs" section of "PrimeStore(R) MTM - Design Control Document" created on October 18, 2025 which was superseded by "Design Output Procedure***" [SOP-DV-005; Rev. 1.0; Effective: 10/27/25]), until during this inspection, as required by 21 CFR 820.30(d). Although the design output section of the "PrimeStore(R) MTM - Design Control Document" states "***(b)(4)***," it fails to require that acceptance criteria be included or referenced and that those design outputs that are essential for the proper functioning of the device are identified.
For example, the following design outputs, created as a part of the "PrimeStore(R) MTM - Design History File (DHF)" (Rev. 1.0; Effective: 10/21/25) at the time the "PrimeStore(R) MTM - Design Control Document" procedure was in effect, fail to contain or make reference to acceptance criteria or identify outputs that are essential for proper functioning of your PrimeStore(R) MTM devices:
* The "Tube system" design output only states "(b)(4)" with no further references to output documentation.
* The "Label set" design output only states "(b)(4)" with no further references to output documentation.
* The "Manufacturing documents" design output only states "(b)(4)" with no further references to output documentation.
* The "Packaging" design output only states "(b)(4)" with no further references to output documentation.
E. Your firm did not have a design review procedure ("Design Reviews" section of "PrimeStore(R) MTM - Design Control Document" created on October 18, 2025 which was superseded by "Design Review Procedure***" [SOP-DV-006; Rev. 1.0; Effective: 10/27/25]), until during this inspection, as required by 21 CFR 820.30(e).
F. Your firm did not have a design verification procedure ("Design Verification***" section of "PrimeStore(R) MTM - Design Control Document" created on October 18, 2025 which was superseded by "Design Verification Procedure ***" [SOP-DV-007; Rev. 1.0; Effective: 10/27/25]), until during this inspection, as required by 21 CFR 820.30(f).
G. Your firm did not have a design validation procedure ("Design Validation***" section of "PrimeStore(R) MTM - Design Control Document" created October 18, 2025 which was superseded by "Design Validation Procedure***" [SOP-DV-008; Rev. 1.0; Effective: 10/27/25]), until during this inspection, as required by 21 CFR 820.30(g).
H. Your firm did not have a design transfer procedure ("Design Transfer to Production" section of "PrimeStore(R) MTM - Design Control Document" created on October 18, 2025 which was superseded by "Design Transfer Procedure***" [SOP-DV-009; Rev. 1.0; Effective: 10/27/25]), until during this inspection, as required by 21 CFR 820.30(h).
I. Your firm did not have a design change procedure ("Change Control***" section of "PrimeStore(R) MTM - Design Control Document" created October 18, 2025 which was superseded by "Design Change Control Procedure***" [SOP-CC-001; Rev. 1.0; Effective: 10/27/25]), until during this inspection, as required by 21 CFR 820.30(i). Although the "Change Control" section of the "PrimeStore(R) MTM - Design Control Document" requires "***(b)(4)***" and "***(b)(4)***," there is no requirement for validation or where appropriate verification, review, and approval of design changes before their implementation.
For example, your firm was unable to provide validation or verification (where appropriate), evidence of review and approval, and assessment for the need of a new premarket authorization submission for the following design changes of your PrimeStore(R) MTM devices prior to implementation:
* Additional tube sizes and fill volume (2mL tube with a 1mL fill volume; 5mL tube with a 1.5mL fill volume; 12mL tube with a 2mL fill volume; and 12mL tube with a 3mL fill volume)
* Change in shelf life prior to use from 24 months to 30 months
* Changes in the tube
J. Your firm failed to define and document a design history file (DHF) ("PrimeStore(R) MTM - Design History File (DHF)" (Rev. 1.0; Effective: 10/21/25) and "DHF - History" dated 10/23/25) for your PrimeStore(R) MTM device, until during this inspection, as required by 21 CFR 820.30(j).
6. Failure to establish and maintain procedures to control product that does not conform to specified requirements, including the identification, documentation, evaluation, segregation, and disposition of nonconforming product. The evaluation of nonconformance shall include a determination of the need for an investigation and notification of the persons or organizations responsible for the nonconformance. The evaluation and any investigation shall be documented, as required by 21 CFR 820.90(a).
Specifically, your firm did not have a procedure to control product that does not conform to specified requirements (QSP-NC-001; Rev. 1; Effective: 10/27/25), until during this inspection. Additionally, your firm failed to identify, document, and evaluate the nonconformances noted in the email dated (b)(4) and (b)(4) from your contract manufacturers regarding (b)(4) underfilled (Lot # (b)(4)) and an unknown quantity of discolored (Lot # (b)(4)) PrimeStore(R) MTM devices, respectively, to determine the need for an investigation. In addition, your firm did not evaluate the need for investigations for the nonconformances associated with 2 leaky caps, 43 specks, and 21 floaters (misc.) of PrimeStore(R) MTM devices (Lot # (b)(4)) which were reworked between (b)(4) and (b)(4).
7. Failure to establish and maintain procedures for rework, to include retesting and reevaluation of the nonconforming product after rework, to ensure that the product meets its current approved specifications and documentation of rework and reevaluation activities, including determination of any adverse effect from the rework upon the product, in the device history record (DHR), as required by 21 CFR 820.90(b)(2).
Specifically, your firm did not have a procedure for rework (QSP-RWK-001; Rev. 1; Effective: 10/27/25), until during this inspection. For example, your firm failed to conduct retesting and reevaluation of the reworks conducted between July 15, 2025 and July 16, 2025 for nonconformances associated with 2 leaky caps, 43 specks, and 21 floaters (or misc.) for your PrimeStore(R) MTM devices (Lot # (b)(4)), to ensure that the product meets its current approved specifications, including a determination of any adverse effect from these reworks.
8. Failure to establish and maintain procedures to ensure that all purchased or otherwise received product and services conform to specified requirements, as required by 21 CFR 820.50.
Specifically, your firm did not have a procedure to ensure that all suppliers conform to specified requirements (QSP-SUP-001; Rev. 1.0; Effective: 10/27/25), until during this inspection. Additionally:
A. Your firm does not establish and maintain requirements, including quality requirements, that must be met by your suppliers, as required by 21 CFR 820.50(a). For example:
1) Your firm does not have documented evaluations that confirm the ability of (b)(4) out of (b)(4) of your suppliers to meet requirements, including quality requirements, as required by 21 CFR 820.50(a)(1). This includes suppliers of the bulk liquid media and plastic components as well as finished device contract manufacturers of your PrimeStore(R) MTM devices.
2) Your firm does not define the type as well as extent of controls to be exercised over your suppliers based on the results of supplier evaluations, as required by 21 CFR 820.50(a)(2).
3) Your firm did not have records of acceptable suppliers ("Longhorn Supplier List" dated 10/28/25), until during this inspection, as required by 21 CFR 820.50(a)(3).
B. Your firm does not have a purchasing agreement in place for (b)(4) out of (b)(4) of the finished device contract manufacturers of your PrimeStore(R) MTM devices which involves an agreement to notify you of changes so that you may determine whether the changes affect the quality of your finished device, as required by 21 CFR 820.50(b).
9. Failure of management with executive responsibility to review the suitability and effectiveness of the quality system at defined intervals and with sufficient frequency according to established procedures to ensure that the quality system satisfies the requirements of this part and the manufacturer's established quality policy and objectives, as required by 21 CFR 820.20(c).
Specifically, your firm did not have a procedure which requires that the management with executive responsibility review the suitability and effectiveness of the quality system at defined intervals and with sufficient frequency to ensure that your quality system satisfies the requirement of the regulation and your quality policy and objectives (QP-MR-001; Rev. 1.0; Effective: 10/27/25), until during this inspection. For example, the management review records retrospectively created for 2022, 2023, and 2024 from emails and memory during the inspection were inadequate because they were non-contemporaneous and based on data from incomplete quality metrics (e.g., nonconforming products, CAPAs, supplier and purchasing controls, etc.).
10. Failure to establish procedures for quality audits and conduct such audits to assure that the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system, as required by 21 CFR 820.22.
Specifically, your firm does not have a quality audit procedure and has not conducted quality audits to assure that your quality system is in compliance with established quality system requirements and to determine the effectiveness of your quality system.
On February 2, 2024, the FDA issued a final rule amending the device current good manufacturing practice (CGMP) requirements of the Quality System (QS) Regulation under 21 CFR 820 to align more closely with the international consensus standard for Quality Management Systems for medical devices used by many other regulatory authorities around the world. The revised part 820, referred to as the Quality Management System Regulation (QMSR), became effective on February 2, 2026. Your most recent inspection from October 20, 2025 through October 30, 2025 was conducted pursuant to the QS Regulation, which was in effect at the time of the inspection. However, any corrective actions you propose or implement must be pursuant to the QMSR requirements in effect as of February 2, 2026. For more information on the QMSR please refer to our frequently asked questions webpage: https://www.fda.gov/medical-devices/quality-system-qs-regulationmedical-device-current-good-manufacturing-practices-cgmp/quality-management-system-regulation-final-rule-amending-quality-system-regulation-frequently-asked.
Medical Device Reporting (MDR) Violations
Our inspection also revealed that your firm's PrimeStore(R) MTM devices are misbranded under section 502(t)(2) of the Act, 21 U.S.C. Sec. 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. Sec. 360i, and 21 CFR Part 803 - Medical Device Reporting. Significant violations include, but are not limited to, the following:
Failure to develop, maintain, and implement written MDR procedures as required by 21 CFR 803.17.
Unapproved Device Violations
Our inspection also revealed that the PrimeStore(R) MTM device is adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. Sec. 351(f)(1)(B), because your firm does not have an approved application for premarket approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C. Sec. 360e(a), or an approved application for an investigational device exemption under section 520(g) of the Act, 21 U.S.C. Sec. 360j(g). The device is also misbranded under section 502(o) the Act, 21 U.S.C. Sec. 352(o), because your firm did not notify the agency of its intent to introduce the device into commercial distribution, as required by section 510(k) of the Act, 21 U.S.C. Sec. 360(k) and 21 CFR 807.81(a)(3)(ii). For a device requiring premarket approval, the notification required by section 510(k) is deemed satisfied when a PMA is pending before the agency. [21 CFR 807.81(b)] The kind of information that your firm needs to submit in order to obtain approval or clearance for the device is described on the Internet at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/default.htm. The FDA will evaluate the information that your firm submits and decide whether the product may be legally marketed.
The PrimeStore(R) MTM was granted marketing authorization following FDA's review of your firm's De Novo request under DEN170029 with the following indications for use:
PrimeStore MTM is intended for the stabilization, transportation and inactivation of infectious unprocessed nasal washes suspected of containing Influenza A virus RNA. PrimeStore MTM is also intended for the stabilization, transportation and inactivation of infectious unprocessed sputum samples suspected of containing Mycobacterium tuberculosis DNA from human samples.
However, your website contains statements and information demonstrating that the PrimeStore MTM is intended for the stabilization and inactivation of numerous additional microorganisms, for the use of numerous additional specimen types and to improve sensitivity in low copy samples outside of the authorized indications. Your website and product brochure also show an intent to market the device for the detection of antimicrobial resistance (AMR) genes. These statements and representations constitute major changes or modifications to the device's intended use, for which your firm lacks clearance or approval. Examples from your firm's website include:
1. A list of additional organisms for which your device is intended for stabilization and inactivation, including Crimean-Congo hemorrhagic fever virus, Eastern equine encephalitis virus, Ebola virus, Mpox, as well as many other organisms. (https://www.lhnvd.com/primestore-mtm and https://www.lhnvd.com/product-development))
2. A statement, "PrimeStore MTM was optimized (and patented) to provide consistent results from simple samples like nasal swabs to the most challenging samples like tissue and stool." (https://www.lhnvd.com/primestore-mtm)
3. A statement, "The USDA recently expanded its use of PrimeStore MTM beyond SARS-CoV-2 and African Swine Fever to facilitate the tracking and surveillance of the avian influenza strain that is infecting wild bird populations and US poultry flocks." (https://www.lhnvd.com/product-development)
Examples from your firm's product brochure for the PrimeStore MTM include:
1. A statement "one device for multiple sample types" which lists 14 different sample types including cervical/vaginal, fecal/stool, urine, blood/plasma/serum, tissue, and genital skin.
2. A statement that the PrimeStore MTM can be used to detect "Viruses," "Parasites,""Bacteria," and "Fungi" and to detect "AMR Genes."
3. A statement, "The device can be used for molecular testing and sequencing of blood,plasma, respiratory samples, urine, tissues and stool in human, animal, avian, plant andenvironmental forensics." (https://www.lhnvd.com/product-development)
These major changes and/or modifications to the intended use of your device could significantly affect the safety and effectiveness of your device as they suggest that your device can stabilize, transport, and inactivate these new sample types and targets not previously reviewed in your De Novo request. Failure to stabilize a specimen and/or failure to inactivate a specimen can result in inaccurate test results as well as in risks to the user handling clinical specimens without appropriate precautions for the specific pathogen.
The performance data provided in your De Novo request indicates the performance of the previously cleared device to inactivate and stabilize nasal washes containing Influenza A virus RNA or unprocessed sputum samples suspected of containing Mycobacterium tuberculosis DNA. However, it does not demonstrate your device's ability to inactivate and stabilize other infectious agents or to be effective to inactivate or stabilize any infectious agent in sample types not addressed in the De Novo. FDA is not aware of any data demonstrating the safety and effectiveness of your device when intended for use with such infectious diseases and sample types. If you have data demonstrating these performance characteristics, please provide that information to the agency in a new premarket submission.
Your firm should take prompt action to address any violations identified in this letter. Failure to adequately address this matter may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and civil money penalties.
Other federal agencies may take your compliance with the Act and its implementing regulations into account when considering the award of federal contracts. Additionally, should FDA determine that you have QS regulation violations that are reasonably related to premarket approval applications for Class III devices, such devices will not be approved until the violations have been addressed. Should FDA determine that your devices or facilities do not meet the requirements of the Act, requests for Certificates to Foreign Governments (CFG) may not be granted.
Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to address the noted violations, as well as an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions (which must address systemic problems) that your firm has taken. If your firm's planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities. If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Your firm's response should be comprehensive and address any violations included in this Warning Letter. If you believe that your products are not in violation of the Act, include your reasoning and any supporting information for our consideration as part of your response.
Your firm's response should be sent via email to Gina Brackett, Establishment Assessment Team 1 Assistant Director at CDRHEnforcement@fda.hhs.gov. Please include in the subject line, "CMS Case 721702" when replying. If you have any questions about the contents of this letter, please contact: Sargum C. Morgan, Compliance Officer at sargum.morgan@fda.hhs.gov.
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm's facility. It is your firm's responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm's manufacturing and quality management systems. Your firm should investigate and determine the causes of any violations and take prompt actions to address any violations and bring the products into compliance.
Sincerely,
/S/ Barbara A. Marsden, Acting Director, Office of Regulatory Programs, Office of Product Evaluation and Quality, Center for Devices and Radiological Health
* * *
Original text here: https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/longhorn-vaccines-and-diagnostics-llc-721702-02262026
FDA Center for Devices & Radiological Health Issues Warning Letter to IsoTis OrthoBiologics
WASHINGTON, March 25 -- The U.S. Department of Health and Human Services Food and Drug Administration issued the following warning letter to IsoTis OrthoBiologics Inc. from its Center for Devices and Radiological Health:* * *
Recipient: Peter P. Nalbach, Vice President and General Manager of Spine Operations, IsoTis OrthoBiologics, Inc., 2 Goodyear, Ste A, Irvine, CA 92618, United States, (b)(4)
Issuing Office: Center for Devices and Radiological Health, United States
WARNING LETTER
CMS #723370
Dear Mr. Nalbach:
During an inspection of your firm located in Irvine, CA from October 6, 2025, ... Show Full Article WASHINGTON, March 25 -- The U.S. Department of Health and Human Services Food and Drug Administration issued the following warning letter to IsoTis OrthoBiologics Inc. from its Center for Devices and Radiological Health: * * * Recipient: Peter P. Nalbach, Vice President and General Manager of Spine Operations, IsoTis OrthoBiologics, Inc., 2 Goodyear, Ste A, Irvine, CA 92618, United States, (b)(4) Issuing Office: Center for Devices and Radiological Health, United States WARNING LETTER CMS #723370 Dear Mr. Nalbach: During an inspection of your firm located in Irvine, CA from October 6, 2025,through October 17, 2025, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufactures resorbable calcium salt bone void filler devices, branded under the Accell Family of products, to include the Accell Evo3c. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. Sec. 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body.
Quality System Regulation Violation(s)
This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. Sec. 351(h), in that the methods used in, or the facilities or controls used for, your manufacture, packing, storage, or installation are not in conformity with the current good manufacturing practice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820.
We received a response from your Director Quality Systems, dated November 7, 2025, concerning our investigator's observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that was issued to your firm. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
1. Failure to adequately establish procedures for corrective and preventive action, as required by 21 CFR 820.100(a). For example:
Your firm failed to adequately take action to correct the cause of nonconformities in order to prevent recurrence. Your firm's corrective and preventative action procedure, Corrective and Preventive Actions CP-1001 Rev. J Effective: 8/22/2022, requires your firm to perform an investigation, determine the need for containment, and assess the risk associated with the issue.
Your firm opened CAPA 157738 on 7/27/23 to address potential (b)(4) particulate contamination occurring during the demineralization process of bone tissue, due to the propeller blade contacting the bottom of the demineralization vessel. The issue was discovered by a manufacturing engineer and documented in emails dating back to 06/22/2023.
As part of CAPA 157738, your firm conducted a risk assessment for the demineralization process. In your risk analysis document, PFMEA-011 Rev. 12, effective October 23, 2023, your firm identified (b)(4) as a risk for particulate contamination. This risk was assigned a severity rating of Moderate and a probability of Improbable, resulting in an overall Acceptable risk rating. Despite discovering that the propeller blade was potentially shedding (b)(4) particles during demineralization, your firm did not investigate whether this finding affected your risk probability rating. In CAPA 157738, your firm classified the risk as low without providing justification for this conclusion and determined that containment action was not required due to your determined low risk. Your firm's CAPA investigation and actions are inadequate because it did not assess the potential impact to finished devices, including distributed product.
Additionally, your firm's Verification of Effectiveness included reviewing 18 work orders to confirm that visual inspection of the propeller was performed. The verification of effectiveness does not demonstrate that visual inspection of the propeller is sufficient to identify potential (b)(4) particulate in your firm's demineralized bone matrix (DBM). Your firm did not verify if the corrective actions performed were sufficient to correct the potential (b)(4) particulate contamination.
Your firm closed CAPA 157738 on 12/17/2024 without evidence that (b)(4) particulate contamination was no longer occurring during your demineralization process.
We reviewed your firm's response and conclude that it is not adequate. While your firm's response acknowledges procedural deficiencies and proposes process improvements, the CAPA defers critical product risk elements to separate CAPAs without clear indication that all deficiencies identified in CAPA-157738 have been adequately addressed. For example, in HHE-(b)(4), your firm identified (b)(4) complaints determined to be relevant now that (b)(4) contamination has been identified as a potential contributing factor. However, none of the related CAPAs indicate whether an MDR assessment was performed for these complaints.
Additionally, it is not clear why the scope of the CAPA retrospective review is from 01/01/2022 to present.
2. Failure to revalidate a validated process when changes or process deviations occurred, as required by 21 CFR 820.75(c). For example:
Your firm's procedure, Validation Program QA-035 Effective: 6/11/21, requires revalidation for previously validated process parameters, component changes, and major design changes; however, your firm did not revalidate your demineralization press when a major design change was made.
Your firm opened CAPA 157738 on 7/27/23 to address a finding that during the manufacturing process of demineralizing bone tissue, the propeller blade contacts the bottom of the demineralization vessel creating the potential shedding of (b)(4) particulates. Two corrective actions were implemented:
* (b)(4)
* (b)(4)
Your firm updated TL-0091 for the Demineralization Press in design change order (DCO), DCO 6306 Released: 5/24/24, which changed the equipment design by (b)(4). Your firm determined that qualification or validation is not required, though the DCO describes the change category as Major. Your firm answered No to the question: Is there a change in the manufacturing equipment while maintaining the existing process? on your Form CPF-0302-001 Decision Tree, although your firm changed the equipment design by (b)(4). Your firm's Director of Quality Systems and Assurance told the investigator that they considered the demineralization press to be a tool and not equipment.
Additionally, your firm determined that (b)(4) inspection was sufficient to identify potential (b)(4) contaminants and required training of your demineralization team to (b)(4) inspect the propellers, however your firm has not validated the (b)(4) inspection process for the propeller blades to demonstrate it is sufficient in identifying potential (b)(4) contaminants in your firm's demineralized bone matrix (DBM). In an email from your firm's manufacturing engineer, they note that (b)(4) particulates are (b)(4).
We reviewed your firm's response and conclude that it is not adequate. Your firm opened CAPA-100520 to address production and process related deficiencies identified in Observation 2. Actions include validating the (b)(4) inspection method with (b)(4) study, completing Installation Qualification for all (b)(4) demineralization assemblies, and establishing preventative maintenance and calibration programs. However, while your firm validated the inspection method and qualified equipment, there is no objective evidence that:
* An evaluation of the existing process validation was conducted to determine if the changes to the demineralization assemblies could impact the applicability of the existing Operational and Performance Qualifications.
* (b)(4) particulate contamination is no longer occurring in production and that the (b)(4)" clearance is sufficient to prevent all contact under all operating conditions
* Testing has been performed to confirm absence of (b)(4) particles in DBM
Furthermore, the verification of effectiveness plan measures compliance to procedures and execution of preventative maintenance but does not include testing for (b)(4) particulates in finished product.
Additionally, it is not clear why the scope identified in CAPA-100520 for reviewing tooling changes is January 2022 to present, when the affected timeframe extends back to 2008.
3. Failure to establish an adequate risk analysis, as required by 21 CFR 820.30(g). For example:
Your firm's procedure, CP-0305 Risk Management Rev. J1 Effective: 5/27/22, requires in Section 6.26.2 Perform Risk Reassessment (As Necessary), that if new or updated risk information is identified, it will be fed back into the risk management system and documented via update and approval of the appropriate risk management forms (such as the Hazard Analysis or FMEA).
Your firm opened CAPA 157738 on 7/27/23 to address a finding, during the manufacturing process of demineralizing bone tissue, the propeller blade contacts the bottom of the demineralization vessel creating potential shedding of (b)(4) particulates. The CAPA identified the risk in PFMEA-001 for OrthoBlast II and PFMEA-002 DynaGraft II as (b)(4) for Supplier error leading to particulate contamination resulting in transient inflammation, which defined a severity of Moderate and a probability occurrence of Improbable, and the Risk Acceptability as Acceptable.
Your firm identified the propeller blade was potentially shedding (b)(4) particulates during the demineralization process; however, your firm did not update PFMEA-001 for OrthoBlast II and PFMEA-002 DynaGraft II to identify this new risk factor. (b)(4) only addresses potential contaminants from your supplier resulting in transient inflammation and does not address the risk of contaminants during your firm's manufacturing processes. Your firm did not identify the risk of (b)(4) contaminants and the potential impact to patient harm. Your firm's risk management files were not updated after identifying this new risk, including identifying the severity of patient harm, as required by your procedure.
Additionally, your firm did not reevaluate the probability of occurrence for potential contaminants. (b)(4) Supplier error leading to particulate contamination resulting in transient inflammation defines a probability occurrence of Improbable. Your firm did not update the occurrence probability after identifying the new risk of potential (b)(4) contaminants.
According to your firm's Senior Manager, New Product Initiatives and Sustaining Engineering, since your firm implemented the demineralized process in 2008, (b)(4) particulates may have been present in your DBM, potentially impacting over (b)(4) devices.
We reviewed your firm's response and conclude that it is not adequate. Your firm opened CAPA-100520 to address risk management deficiencies identified in Observation 3. Although your firm acknowledges that risk assessment associated with CAPA 157738 and related PFMEAs and Hazard Analysis (HA-(b)(4)) required revision and initiated procedural changes, your response is still inadequate. Your firm's actions included:
* Updated PMFEAs ((b)(4)) to include (b)(4)
* Updated Hazard Analysis HA-(b)(4) to (b)(4)
* Conducted a retrospective Health Hazard Evaluation (HHE-(b)(4))
HHE-(b)(4) concluded that no correction, removal, or recall recommended, as the risk level assessed as Low and Acceptable. Your firm acknowledges that (b)(4) contamination occurred from 2008-2024, with over (b)(4) devices potentially affected, however no actual testing was performed to confirm the absence of (b)(4) in distributed product. The HHE is deficient in that:
* Your firm reviewed (b)(4) complaints and deemed (b)(4) clinically relevant for your probability calculation. There was no clear indication on which were not deemed clinically relevant and why. Your firm concluded that (b)(4) complaints related to (b)(4) contamination without adequately documenting an investigation showing how they ruled out (b)(4) contamination as a contributing factor.
* Your firm's Probability Assessment disregards potential inflammation or foreign body reaction due to (b)(4) particles as typical post-surgical inflammation
* Severity Assessment deemed Moderate, which firm has defined in your firm's procedure, Risk Management Rev. J1 Effective: 5/27/22 and identified in the Severity Ratings Table in HHE-(b)(4) as a minor intervention (i.e. Medical intervention that may result in procedural delay, requiring removal and re-insertion of device resulting in additional patient discomfort or increased anesthesia requirements; Minor, transient, or self-limiting injury not requiring medical intervention; Cancellation of an elective medical procedure / surgery). While complaint data included in HHE includes revision surgery, hospitalization, IV antibiotics, osteolysis consistent with a higher severity rating as noted in your procedure.
* Biocompatibility has not been adequately evaluated. Your firm states that (b)(4) is used in permanently implanted devices (stents, pledgets, endoprostheses), therefore, (b)(4) exposure is not expected to cause adverse effects. However, the cited devices use intact (b)(4) structures, not particulate contamination. Your firm provides no data demonstrating that they have:
o Characterized potential particle generation during normal use and wear.
o Conducted biocompatibility testing per ISO 10993 standards if particle release is expected.
o Assessed the clinical significance of any particle elution through risk analysis.
Your firm should take prompt action to address any violations identified in this letter. Failure to adequately address this matter may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and civil money penalties.
On February 2, 2024, the FDA issued a final rule amending the device current good manufacturing practice (CGMP) requirements of the Quality System (QS) Regulation under 21 CFR 820 to align more closely with the international consensus standard for Quality Management Systems for medical devices used by many other regulatory authorities around the world. The revised part 820, referred to as the Quality Management System Regulation (QMSR), became effective on February 2, 2026. Your most recent inspection on October 6, 2025 through October 17, 2025 was conducted pursuant to the QS Regulation, which was in effect at the time of the inspection. However, any corrective actions you propose, or implement must be pursuant to the QMSR requirements in effect as of February 2, 2026. For more information on the QMSR please refer to our frequently asked questions webpage: https://www.fda.gov/medical-devices/quality-system-qs-regulationmedical-device-current-good-manufacturing-practices-cgmp/quality-management-system-regulation-final-rule-amending-quality-system-regulation-frequently-asked.
Other federal agencies may take your compliance with the FD&C Act and its implementing regulations into account when considering the award of federal contracts. Additionally, should FDA determine that you have Quality System regulation violations that are reasonably related to premarket approval applications for Class III devices, such devices will not be approved until the violations have been addressed. Should FDA determine that your devices or facilities do not meet the requirements of the Act, requests for Certificates to Foreign Governments (CFG) may not be granted.
Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to address the noted violations, as well as an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions (which must address systemic problems) that your firm has taken. If your firm's planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities. If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Your firm's response should be comprehensive and address any violations included in this Warning Letter. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration as part of your response.
Your firm's response should be sent via email to CDRHEnforcement@fda.hhs.gov. Please include in the subject line, "CMS Case 723370" when replying. If you have any questions about the contents of this letter, please contact: Shaquenta Perkins at shaquenta.perkins@fda.hhs.gov.
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm's facility. It is your firm's responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm's manufacturing and quality management systems. Your firm should investigate and determine the causes of any violations and take prompt actions to address any violations and bring the products into compliance.
Sincerely,
/S/ Barbara C. Marsden, Acting Director, Office of Regulatory Programs, Office of Product Evaluation and Quality, Center for Devices and Radiological Health
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Original text here: https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/isotis-orthobiologics-inc-723370-02242026