Delivery Method:Via EmailProduct:DrugsRecipient:Shabdan AkylbekovHyaluron Pen Store, LLC dba Glow Nest Beauty3700 S Iron StChicago,IL60609United Statesteam@hyaworld.storeIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWARNING LETTERMarch 3, 2025Glow Nest Beauty339 Abington Woods Drive,Aurora IL, 60502glownestbeauty@gmail.comRE: 700256Dear Shabdan Akylbekov:This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your websites at the internet addresses https://www.glownestbeauty.com/ and https://www.hyaworld.store/ in January 2025 and has observed that your websites offers various injectable lipolytic products such as “PineBottle,” “Super V-Line Sol,” “LipoLab PPC Solution (brown bottle),” and “Deolipo” for sale in the United States. We have also reviewed your social media websites at https://www.facebook.com/hyaluronpenoriginal/ and https://www.instagram.com/glownestbeauty/. Your social media websites direct consumers to your https://www.glownestbeauty.com/ and/or https://www.hyaworld.store/ websites to purchase your products. As described below, your injectable lipolytic products including “PineBottle,” “Super V-Line Sol,” “LipoLab PPC Solution (brown bottle),” and “Deolipo” are unapproved new drugs introduced or delivered for introduction into interstate commerce in violation of sections 505(a) and 301(d) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a) and 331(d).These products are especially concerning from a public health perspective because injectable drug products can pose risks of serious harm to users. Injectable products are delivered directly into the body, sometimes directly into the bloodstream, and therefore, bypass some of the body’s key defenses against toxins and microorganisms that can lead to serious and life-threatening conditions.Your products are drugs as defined by section 201(g)(1) of the FD&C Act, 21 U.S.C. 321(g)(1), because they are intended to prevent, treat, or cure disease conditions and/or affect the structure or function of the body. Examples of claims observed on your websites that establish the intended use of your products as drugs for human use include, but may not be limited to, the following:PineBottleOn your webpage https://www.glownestbeauty.com/product-page/pinebottle-fat-burber:???? “Enhance Skin Elasticity, Reduce Wrinkles. Pine Bottle enhances skin elasticity and reduces wrinkles. Unlike typical lipolysis products that can cause wrinkles”???? “During fat dissolution, our solution, combined with Riboflavin, Cyanocobalamin, and L-Carnitine, accelerates lipolysis, [s]afely dissolving fat cells and addressing potential wrinkles.”Super V-Line SolOn your webpages https://www.glownestbeauty.com/product-page/super-v-line-sol and https://www.hyaworld.store/shop#!/Super-V-Line-Sol/p/586905325:???? “[I]ntended for removing fat deposits from different facial zones. After the procedure the skin gets lifted and facial contours obtain delicate V-shape.”???? “Removes fat deposits and lifts the skin simultaneously.”???? “Speeds up regeneration and skin renewal processes.”???? “It is used on contour plastics for correcting facial contours.”On a February 19, 2024 post on your Instagram social media website at https://www.instagram.com/glownestbeauty:???? “Lipolytic”???? “Tightens the skin and improves elasticity.”???? “Removes the formation of fat in the chin, cheeks, ears, nose, hernias around the eyes.”???? “Promotes skin regeneration, creates a lifting effect.”LipoLab PPC Solution (brown vial)On your webpages https://www.glownestbeauty.com/product-page/+ LipoLab-fatdissolver and https://www.hyaworld.store/#!/+ LipoLab/p/610135630:???? “[O]ne of the safest and most effective fat dissolving products in existence today. It offers fast subcutaneous fat removal. It fights obesity in two main ways - by speeding up metabolism and melting the fat tissues in a natural and health-friendly manner. This PPC (Phosphatidyl Choline) solution can also increase the elasticity of the skin and remove cellulite.”???? “More efficacious, easier treatment and cheaper than liposuction surgery.”???? “Unlike existing methods such as mesotherapy which only reduces the size of fat cells, Lipo Lab PPC dissolves, destroys fat cells and exhausts them out of the body through sweat, urine and internal combustion.”???? “Effective for removing cellulites and enhances skin elasticity”???? “Promotes adipocytes”On a November 13, 2024 post on your Instagram social media website at https://www.instagram.com/glownestbeauty:???? “[L]ipolytic”???? “[D]rugs for correction of excess adipose tissue.”???? “They are injected under the skin and allow you to remove fat deposits locally.”???? “The technique itself can not only get rid of excess, but also improve the condition of the skin, restore metabolism in tissues.”???? “Fat is converted into an emulsion, then into water and the body easily removes it naturally.”On a February 9, 2022 post on your Facebook social media website at https://www.facebook.com/hyaluronpenoriginal/:???? “Lipo Lab is a safe and effective lipolytics [sic] designed to activate the breakdown of fat cells and remove them from the body.”???? “A lipolytic destroys cell membranes by converting the fat in the cells into an emulsion.”On a July 10, 2023 post on your Facebook social media website at https://www.facebook.com/hyaluronpenoriginal/:???? “The Ultimate Fat Burner! Ignite Your Fat Burning Potential! Are you tired of struggling with stubborn fat that just won’t budge? Say goodbye to your worries because Lipolab is here to rescue you!”???? “[R]amp up your metabolism, turning your body into a fat-burning machine . . . excess pounds melt away!???? “[H]elps enhance endurance and stamina.”DeolipoOn your webpages https://www.glownestbeauty.com/product-page/deolipo and https://www.hyaworld.store/#!/Deolipo/p/586901883:???? “DEOLIPO is an innovative contouring serum that's specifically designed to enhance the appearance and profile of moderate to severe fat on the face or body. By inducing a reduction in redundant lipids or fat, DEOLIPO helps provide a natural and well-defined line that complements your facial features or body shape.”???? “DEOLIPO serves as a supportive aid for the treatment of various forms of obesity, including the most common dyslipidemias that often accompany this condition. Its main ingredient, deoxycholic acid, is an FDA-approved fat dissolving material and a human bile acid that's produced by intestinal bacteria in the human body.”On a February 15, 2024 post on your Instagram social media website at https://www.instagram.com/glownestbeauty:???? “Completely removes excess fat without the need for any operations”Your “PineBottle,” “Super V-Line Sol,” “LipoLab PPC Solution (brown bottle),” and “Deolipo” products are not generally recognized as safe and effective for the above referenced uses and, therefore, are “new drugs” under section 201(p) of the FD&C Act, 21 U.S.C. 321(p). Subject to certain exceptions not applicable here, new drugs may not be legally introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect, as described in sections 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(d) and 355(a). No approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355 are in effect for these products. Accordingly, the introduction or delivery for introduction into interstate commerce of these products violates sections 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(d) and 355(a).ConclusionThis letter is not intended to be an all-inclusive statement of violations that may exist in connection with your products. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.This letter notifies you of our concerns and provides you an opportunity to address them. Failure to adequately address this matter may result in legal action including, without limitation, seizure and injunction.Please notify FDA in writing, within fifteen working days of receipt of this letter, of the specific steps you have taken to correct any violations. Include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. 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. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the time within which you will complete the correction.Your response should be sent to U.S. Food and Drug Administration, CDER/OC/Office of Unapproved Drugs and Labeling Compliance by email to FDAADVISORY@fda.hhs.gov. Please include your firm name and the unique identifier “700256” in the subject line of the email.Sincerely,/S/Tina Smith, M.S.Captain, U.S. Public Health ServiceDirectorOffice of Unapproved Drugs and Labeling ComplianceOffice of ComplianceCenter for Drug Evaluation and ResearchFood and Drug Administration

Delivery Method:Via EmailProduct:DrugsRecipient:Julie EllisJulian Naya Beauty LLC1298 Antwerp LaneSan Jose,CA95118United StatesInfo@juliannayabeauty.comIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWARNING LETTERMarch 3, 2025RE: 699782Dear Julie Ellis:This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your website at the internet address https://juliannayabeauty.com/ in January 2025 and has observed that your website offers various injectable lipolytic products such as “Kabelline,” “Lipo Lab PPC Solution,” “Lipo Lab V-Line,” “LemonBottle Ampoule Solution,” “Lipo Vela,” and “Neobella” for sale in the United States. We have also reviewed your social media websites at https://www.facebook.com/juliannayabeauty/ and https://www.instagram.com/juliannayabeauty/. Your social media websites direct consumers to your https://juliannayabeauty.com/ website to purchase your products. Asdescribed below, your “Kabelline,” “Lipo Lab PPC Solution,” “Lipo Lab V-Line,” “LemonBottle Ampoule Solution,” “Lipo Vela,” and “Neobella” products are unapproved new drugs introduced or delivered for introduction into interstate commerce in violation of sections 505(a) and 301(d) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a) and 331(d).These products are especially concerning from a public health perspective because injectable drug products can pose risks of serious harm to users. Injectable products are delivered directly into the body, sometimes directly into the bloodstream, and therefore, bypass some of the body’s key defenses against toxins and microorganisms that can lead to serious and life-threatening conditions.Your products are drugs as defined by section 201(g)(1) of the FD&C Act, 21 U.S.C. 321(g)(1), because they are intended to prevent, treat, or cure disease conditions and/or affect the structure or function of the body. Examples of claims observed on your website and social media websites that establish the intended use of your products as drugs for human use include, but may not be limited to, the following:On your “Kabelline” webpage https://juliannayabeauty.com/product/kabelline/:???? “Kabelline is one of the highest-rated fat dissolver [sic] on the market. Kabelline Fat Reduction Solution is a contouring solution that helps to improve the appearance and profile of moderate to severe fat on the body. Kabelline products include the active ingredient synthetic deoxycholic acid. Deoxycholic acid aids in the breakdown of fat and its absorption; it is a naturally occurring body molecule.”???? An image of application sites on a woman’s body with the quote “Point Injection Apply 0.2-0.3ml at each point.”On your “Lipo Lab PPC Solution” webpage https://juliannayabeauty.com/product/lipolab/:???? “It efficiently eliminates fat deposits and cellulite in different parts of the body. LipoLab is one of the safest and most effective fat dissolving products in existence today. It offers fast subcutaneous fat removal. It fights obesity in two main ways – by speeding up metabolism and melting the fat tissues in a natural and health-friendly manner.”???? “Areas recommended for injection are: - double chin - shoulders and forearms - armpits - back and abdomen - lateral folds - buttock - knees”On your “Lipo Lab V-Line” webpage https://juliannayabeauty.com/product/lipo-lab-vline/:???? “This advanced product helps redefine facial contours by breaking down fat cells”???? “Benefits and Effects . . . Facial fat reduction”???? “Inject into the subcutaneous fat layer: Use a thin needle to inject the solution into the subcutaneous fat layer”On your “LemonBottle Ampoule Solution” webpage https://juliannayabeauty.com/product/lemonbottlefat/:???? “LEMONBOTTLE is a high-concentration, premium solution combining Riboflavin (Vitamin B2) with advanced fat-decomposition ingredients. This innovative formula boosts fat cell metabolism, accelerates their breakdown, and enhances lipase activity, all while soothing inflammation.”???? Image of a syringe and human arm with the quote “Under Arms.” Similar images for “Abdomen,” “Love Handle,” “Outer Thighs,” and “Inner Thighs.”On your “Lipo Vela” webpage https://juliannayabeauty.com/product/lipo-vela/#:???? “LIPO VELA is a high-purity PPC solution designed for enhanced fat reduction. Enriched with Sodium Deoxycholate, L-carnitine, and vitamin B12, it accelerates lipolysis, effectively and safely dissolving fat cells while promoting fat cell metabolism.”???? “Permanently Eliminates Fat Cells”On your “Neobella” webpage https://juliannayabeauty.com/product/neobella/:???? “Permanent fat removal and skin tightening in one system. Dissolve localized fat and cellulite.”???? “With the help of Deoxycholic Acid, the Neobella injection triggers a natural lipolytic process, encouraging the organism to dissolve fatty acids stored in the target treatment zones.”On your Facebook social media website at https://www.facebook.com/juliannayabeauty/:???? November 15, 2024 post: “V-Line Solution Premium Lab V-Line is an advanced, non-surgical treatment designed for facial contouring and lifting, specifically optimized for facial applications. This innovative fat-dissolving lipolysis solution delivers superior results compared to traditional liposuction surgery.”On your Instagram social media website at https://www.instagram.com/juliannayabeauty/:???? April 4, 2022 post: “Kabeline Fat Dissolver Get Rid of Fat, Permanently!”On your Facebook and Instagram social media websites at https://www.facebook.com/juliannayabeauty/ and https://www.instagram.com/juliannayabeauty/:???? September 12, 2024 post: “Lemon Bottle Fat Dissolving Injections”Your “Kabelline,” “Lipo Lab PPC Solution,” “Lipo Lab V-Line,” “LemonBottle Ampoule Solution,” “Lipo Vela,” and “Neobella” products are not generally recognized as safe and effective for the above referenced uses and, therefore, are “new drugs” under section 201(p) of the FD&C Act, 21 U.S.C. 321(p). Subject to certain exceptions not applicable here, new drugs may not be legally introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect, as described in sections 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(d) and 355(a). No approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, are in effect for these products. Accordingly, the introduction or delivery for introduction into interstate commerce of these products violates sections 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(d) and 355(a).ConclusionThis letter is not intended to be an all-inclusive statement of violations that may exist in connection with your products. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.This letter notifies you of our concerns and provides you an opportunity to address them. Failure to adequately address this matter may result in legal action including, without limitation, seizure and injunction.Please notify FDA in writing, within fifteen working days of receipt of this letter, of the specific steps you have taken to correct any violations. Include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. 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. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the time within which you will complete the correction.Your response should be sent to U.S. Food and Drug Administration, CDER/OC/Office of Unapproved Drugs and Labeling Compliance by email to FDAADVISORY@fda.hhs.gov. Please include your firm name and the unique identifier “699782” in the subject line of the email.Sincerely,/S/Tina Smith, M.S.Captain, U.S. Public Health ServiceDirectorOffice of Unapproved Drugs and Labeling ComplianceOffice of ComplianceCenter for Drug Evaluation and ResearchU.S. Food and Drug Administration

Delivery Method:Via EmailProduct:DrugsRecipient:Lisa L. CurrinVivid-Scientific LLC203 East Main StreetJamestown,NC27282United Statessupport@vividscientific.comvividscientificllc@gmail.comIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWARNING LETTERMarch 3, 2025RE: 699226Dear Lisa Currin:This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your website at the internet address https://www.vividscientific.com/ in January 2025 and has observed that your website offers various injectable lipolytic products, such as “LemonBottle Ampoule Solution,” “Lipo Lab PPC Solution,” “Neobella Extreme,” and “Deoxycholic Acid Booster,” for sale in the United States. As described below, your “LemonBottle Ampoule Solution,” “Lipo Lab PPC Solution,” “Neobella Extreme,” and “Deoxycholic Acid Booster” products are unapproved new drugs introduced or delivered for introduction into interstate commerce in violation of sections 505(a) and 301(d) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a) and 331(d).These products are especially concerning from a public health perspective because injectable drug products can pose risks of serious harm to users. Injectable products are delivered directly into the body, sometimes directly into the bloodstream, and therefore, bypass some of the body’s key defenses against toxins and microorganisms that can lead to serious and life-threatening conditions.Your products are drugs as defined by section 201(g)(1) of the FD&C Act, 21 U.S.C. 321(g)(1), because they are intended to prevent, treat, or cure disease conditions and/or affect the structure or function of the body. Examples of claims observed on your websites that establish the intended use of your products as drugs for human use include, but may not be limited to, the following:On your “LemonBottle Ampoule Solution” webpage https://www.vividscientific.com/lemonbottle-fat-dissolver-5-vials--no-kit.html:???? “FAT DISSOLVER”???? “The plant and vitamin based formulation dissolves localized cellulite and fat, tightens skin, and improves overall health.”???? “Dissolve Fat & Cellulite - immediately breaks down fat cells (including cellulite) and speeds up metabolism.”???? “Anti Aging – Centella Asiatica extract stimulates collagen, has anti-inflammatory properties, and is an excellent antioxidant”???? “Increased Metabolism & Energy – Riboflavin (Vit B2) specializes in extracting energy from food while burning fat + functions as an antioxidant supporting the immune system, healthy skin, and hair.”On your “Lipo Lab PPC Solution” webpage https://www.vividscientific.com/LipoLab-Max-NO-KIT_p_57.html:???? “Permanently dissolve fat and cellulite while increasing collagen and elastin with Lipo Lab's proprietary lipolysis formula.”???? “Treatment with Lipo Lab produces rapid fat loss and prevents wrinkles and sagging as the fat layer shrinks.”???? “Dissolve stubborn fat and cellulite”???? “Increase metabolism”???? “Boost energy levels”???? “[S]odium deoxycholate breaks down the membranes of fat cells allowing phosphatidylcholine (PPC) to enter and dissolve fatty acid molecules.”???? “L-carnitine, the third active ingredient, acts as a carrier molecule, facilitating the transport of fatty acids into the mitochondria, where they are converted into energy.”???? “The active ingredients are naturally occurring molecules that dissolve fat and cellulite permanently. Treated fat cells can no longer store fat.”On your “Neobella Extreme” webpage https://www.vividscientific.com/NEOBELLAEXTREME-5-VIALS-NO-KIT_p_64.html:???? “Target stubborn cellulite and fatty problem areas. . . . Results are permanent! Once the fat cells are dissolved, they are gone for good.”???? “PERMANENT FAT REMOVAL + SKIN TIGHTENING IN ONE SYSTEM.”???? “Fat dissolving injections provide a non-surgical, gentle method of sculpting the body gradually and artistically.”???? “The main active ingredient is deoxycholic acid, a naturally occurring molecule that breaks down and destroys fat.”On your “Deoxycholic Acid Booster” webpage https://www.vividscientific.com/deoxycholic-acid-fat-dissolving-booster-10ml.html:???? “DEOXYCHOLIC ACID FAT DISSOLVING BOOSTER contains the same deoxycholic acid formulation as KYBELLA.”???? “The BOOSTER can be added to lipolysis serums (Neobella, LipoLab, etc.) to increase efficacy and accelerate results.”Your “LemonBottle Ampoule Solution,” “Lipo Lab PPC Solution,” “Neobella Extreme,” and “Deoxycholic Acid Booster” products are not generally recognized as safe and effective for the above referenced uses and, therefore, are “new drugs” under section 201(p) of the FD&C Act, 21 U.S.C. 321(p). Subject to certain exceptions not applicable here, new drugs may not be legally introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect, as described in sections 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(d) and 355(a). No approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, are in effect for these products. Accordingly, the introduction or delivery for introduction into interstate commerce of these products violates sections 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(d) and 355(a).ConclusionThis letter is not intended to be an all-inclusive statement of violations that may exist in connection with your products. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.This letter notifies you of our concerns and provides you an opportunity to address them. Failure to adequately address this matter may result in legal action including, without limitation, seizure and injunction.Please notify FDA in writing, within fifteen working days of receipt of this letter, of the specific steps you have taken to correct any violations. Include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. 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. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the time within which you will complete the correction.Your response should be sent to U.S. Food and Drug Administration, CDER/OC/Office of Unapproved Drugs and Labeling Compliance by email to FDAADVISORY@fda.hhs.gov. Please include your firm name and the unique identifier “699226” in the subject line of the email.Sincerely,/S/Tina Smith, M.S.Captain, U.S. Public Health ServiceDirectorOffice of Unapproved Drugs and Labeling ComplianceOffice of ComplianceCenter for Drug Evaluation and ResearchFood and Drug Administration

Product:DrugsRecipient:USApeptide.comGermanyIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesFROM: The United States Food and Drug AdministrationRE: Notice of Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the InternetDATE: February 26, 2025WARNING LETTERThis is to advise you that the United States (U.S.) Food and Drug Administration (FDA) recently reviewed your website at the Internet address www.usapeptide.com and has observed that your website introduces into interstate commerce misbranded and unapproved new drugs in violation of sections 301(a), 301(d), 301(k), 503(b), and 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) [21 U.S.C. §§ 331(a), 331(d), 331(k), 353(b), and 355(a)].As discussed below, FDA has observed that www.usapeptide.com introduces into interstate commerce unapproved and misbranded semaglutide and tirzepatide drug products. There are inherent risks to consumers who purchase unapproved new drugs and misbranded drugs. Unapproved new drugs do not carry the same assurances of safety and effectiveness as those drugs subject to FDA oversight. Drugs that have circumvented regulatory safeguards may be contaminated, counterfeit, contain varying amounts of active ingredients, or contain different ingredients altogether. Accordingly, FDA requests that www.usapeptide.com cease offering any unapproved and misbranded drugs for sale to U.S. consumers. This is critical to protect the public from harm.Unapproved New Drugs:Despite statements on your product labeling and website such as “research use only,” “not for human consumption,” “lab purposes only,” and “not intended to diagnose, cure, mitigate, treat or prevent disease,” evidence obtained from your website establishes that certain products offered for sale by www.usapeptide.com are drugs intended for human use.Examples of claims from the products’ labeling, including on your website listed above, that provide evidence of the intended use (as defined in 21 CFR 201.128) of these products as drugs for human use includes the following:Semaglutide (GLP-1 Analogue) 5mg and Semaglutide (GLP-1 Analogue) 10mg: “Semaglutide, also marketed under the brand names Ozempic, Rybelsus and Wegovy, is an FDA-approved injectable for weight loss…” “Semaglutide is a potent once-weekly GLP-1 RA, significantly reducing HbA1c, body weight and systolic blood pressure.”5mg Tirzepatide (Mounjaro) 5mg and 10mg Tirzepatide (Mounjaro) 10mg: “… recently approved in the US to help type 2 diabetes patients better manage blood sugar.” “Tirzepatide is a compound that has been shown to help with weight loss…” “… stimulates the release of hormones that signal the brain to reduce food intake and increase feelings of fullness.”These products are drugs within the meaning of section 201(g) of the FD&C Act [21 U.S.C. § 321(g)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease and/or because they are intended to affect the structure or function of the body. These drugs are also new drugs as defined by section 201(p) of the FD&C Act [21 U.S.C. § 321(p)], because they are not generally recognized as safe and effective for their labeled uses. With certain exceptions not applicable here, new drugs may not be legally introduced or delivered for introduction into interstate commerce without prior approval from FDA, as described in section 505(a) of the FD&C Act [21 U.S.C. § 355(a)]. No approved applications pursuant to section 505 of the FD&C Act are in effect for these products. Accordingly, their introduction or delivery for introduction into interstate commerce violates sections 301(d) [21 U.S.C. § 331(d)] and 505(a) of the FD&C Act.On www.usapeptide.com, you offer semaglutide marketed as “Semaglutide (GLP-1 Analogue) 5mg” and “Semaglutide (GLP-1 Analogue) 10mg.” While there are FDA-approved versions of semaglutide on the market in the U.S., there are no approved drug applications pursuant to section 505 of the FD&C Act in effect for the “Semaglutide (GLP-1 Analogue) 5mg” and “Semaglutide (GLP-1 Analogue) 10mg” offered by www.usapeptide.com. Currently there are three semaglutide products that are FDA-approved for the U.S. market and these products are only available pursuant to a prescription from a licensed practitioner. FDA-approved semaglutide injection marketed under the brand name Ozempic is indicated as an adjunct to diet and exercise to improve glycemic control in individuals with type 2 diabetes mellitus and to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease. FDA-approved semaglutide injection marketed under the brand name Wegovy is indicated as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management in certain adult and pediatric patients. FDA-approved semaglutide tablets marketed under the brand name Rybelsus are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. FDA-approved semaglutide products bear a boxed warning, commonly referred to as a “black box warning,” which is the strongest warning FDA requires, indicating that the drug carries a significant risk of serious or even life-threatening adverse effects. The boxed warning addresses the risk of thyroid C-cell tumors.In addition, on www.usapeptide.com you offer tirzepatide marketed as “5mg Tirzepatide (Mounjaro) 5mg” and “10mg Tirzepatide (Mounjaro) 10mg.” While there are FDA-approved tirzepatide products on the market in the U.S., there are no approved drug applications pursuant to section 505 of the FD&C Act in effect for the 5mg Tirzepatide (Mounjaro) 5mg” and “10mg Tirzepatide (Mounjaro) 10mg” offered by www.usapeptide.com. Currently there are two tirzepatide products that are FDA-approved for the U.S. market and these products are only available pursuant to a prescription from a licensed practitioner. FDA-approved tirzepatide injection marketed under the brand name Mounjaro is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. FDA-approved tirzepatide injection marketed under the brand name Zepbound is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in certain adult patients. FDA-approved tirzepatide also bears a boxed warning addressing the risk of thyroid C-Cell tumors.Misbranded Drugs:A drug is misbranded under section 502(f)(1) of the FD&C Act [21 U.S.C. § 352(f)(1)] if its labeling fails to bear adequate directions for use. “Adequate directions for use” means directions under which a layperson can use a drug safely and for the purposes for which it is intended (see 21 CFR 201.5). Prescription drugs, as defined in section 503(b)(1) of the FD&C Act [21 U.S.C. § 353(b)(1)] include those that, because of their toxicity or other potentiality for harmful effect, or the method of their use, or the collateral measures necessary for their use, are not safe for use except under supervision of a practitioner licensed by law to administer them. Prescription drugs, as defined in section 503(b)(1) of the FD&C Act, can be used safely only at the direction, and under the supervision, of a licensed practitioner.Because the aforementioned drugs are prescription drugs intended for conditions that are not amenable to self-diagnosis and treatment by a layperson, adequate directions cannot be written such that a layperson can use the products safely for their intended use. Consequently, the labeling for these drugs fails to bear adequate directions for use, causing them to be misbranded under section 502(f)(1) of the FD&C Act. In addition, because the drugs are not approved in the U.S., they are also not exempt under 21 CFR 201.115(a) from the requirements of section 502(f)(1) of the FD&C Act. By offering these drugs for sale to U.S. consumers, www.usapeptide.com is causing the introduction of misbranded drugs into interstate commerce in violation of section 301(a) of the FD&C Act [21 U.S.C. § 331(a)].Additionally, “Semaglutide (GLP-1 Analogue) 5mg,” “Semaglutide (GLP-1 Analogue) 10mg,” “5mg Tirzepatide (Mounjaro) 5mg,” and “10mg Tirzepatide (Mounjaro) 10mg” offered by www.usapeptide.com are intended for injection, which heightens the public health concern associated with these products and may further contribute to the potential for patient harm. On www.usapeptide.com you offer “Bacteriostatic Water 20ml Vial” and “10 PACK OF INSULIN SYRINGES ASST. SIZES.” Injectable drug products can pose a serious risk of harm to users because they bypass many of the body’s natural defenses against toxic ingredients, toxins, or dangerous organisms that can lead to serious and life-threatening conditions such as septicemia or sepsis.Furthermore, under U.S. law, prescription drugs can be dispensed only pursuant to a prescription from a healthcare practitioner licensed by law to administer prescription drugs. By offering the aforementioned drugs without requiring a prescription, www.usapeptide.com jeopardizes patient safety and misbrands the drugs under section 503(b)(1) of the FD&C Act. Dispensing a prescription drug without a prescription is an act which results in the drug being misbranded while held for sale, in violation of section 301(k) of the FD&C Act [21 U.S.C. § 331(k)].FDA is sending this warning letter to www.usapeptide.com because of the inherent risks to consumers who purchase misbranded and unapproved new drugs. This letter is not intended to identify all the ways in which your products or operations might be in violation of the law. It is your responsibility to ensure that all products you offer for sale are in compliance with the FD&C Act and its implementing regulations. You should take prompt action to address any violations of the FD&C Act (which may include the offer for sale of similarly misbranded and/or unapproved new drugs other than the drugs noted above). We advise you to review your websites, product labels, and other labeling and promotional materials to ensure that you are not misleadingly representing your products as safe and effective for a use for which they have not been approved by FDA and that you are not distributing misbranded products in violation of the FD&C Act.Please notify this office in writing within 15 working days describing the specific steps you have taken to address any violations and to prevent their recurrence. Include an explanation of each step being taken to remedy and prevent the recurrence of any violations, as well as copies of related documentation. Failure to adequately address this matter may result in legal action, including, without limitation, seizure and injunction, without further notice. If you cannot complete corrective action within 15 working days, state the reason for the delay and the time within which you will complete the corrections. This letter notifies you of our concerns and provides you with an opportunity to address them. 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 within 15 working days.If you are not located in the U.S., please note that products that appear to be misbranded or unapproved new drugs may be detained or refused admission. We may advise the appropriate regulatory officials in the country from which you operate that your products referenced above appear to be unapproved and misbranded products that cannot be legally sold to consumers in the U.S.Please direct your response and any inquiries to FDA at FDAInternetPharmacyTaskForce-CDER@fda.hhs.gov.Sincerely,/S/S. Leigh Verbois, Ph.D.Director, Office of Drug Security, Integrity, and ResponseOffice of ComplianceCenter for Drug Evaluation and Research

Delivery Method:Via EmailProduct:DrugsRecipient:Andy JassyCEOAmazon.com, Inc.410 Terry Ave. NSeattle,WA98109-5210United StatesRegulatory-inquiries@amazon.coIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWARNING LETTERMarch 3, 2025RE: 695821Dear Mr. Jassy:This letter concerns your firm’s distribution of products that violate the Federal Food, Drug, and Cosmetic Act (the “FD&C Act”). The United States Food and Drug Administration (FDA) reviewed injectable lipolytic drug products that were purchased on your website, www.amazon.com. As discussed further below, your firm is responsible for introducing or delivering for introduction into interstate commerce these products, which are unapproved new drugs under section 505(a) of the Federal Food, Drug, and Cosmetic Act (the “FD&C Act”), 21 U.S.C. 355(a). As explained further below, introducing or delivering these products for introduction into interstate commerce is prohibited under sections 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(d) and 355(a).FDA purchased “LemonBottle Ampoule Solution,” “L-Carnitine Body Serum Ampoule,” and “Matrigen PPC Ampoule” through your website, www.amazon.com. These products, which are drugs as defined by section 201(g)(1) of the FD&C Act, 21 U.S.C. 321(g)(1), were introduced or delivered for introduction into interstate commerce by Amazon via your Fulfillment by Amazon service.1These products are especially concerning from a public health perspective because injectable drug products can pose risks of serious harm to users. Injectable products are delivered directly into the body, sometimes directly into the bloodstream, and therefore, bypass some of the body’s key defenses against toxins and microorganisms that can lead to serious and life-threatening conditions.Unapproved New Drugs“LemonBottle Ampoule Solution,” “L-Carnitine Body Serum Ampoule,” and “Matrigen PPC Ampoule” are drugs as defined by section 201(g)(1) of the FD&C Act, 21 U.S.C. 321(g)(1) because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease and/or intended to affect the structure or any function of the body.Examples of claims observed on the labeling that establish the intended use of these products as drugs include, but may not be limited to, the following:LemonBottle Ampoule SolutionThe QR code sticker on the product package directs to the URL website, https://makesolutions.kr/?A=453691044904, which includes a link to the website, www.lemonbottle.net, which redirects consumers to the website, www.sidmedicos.com.From www.sidemedicos.com:???? “LEMONBOTTLE LIPOLYSIS”???? “How LEMONBOTTLE Treatment works and why it is safety [sic] . . . howLEMON BOTTLE DISSOLVES fat . . .Riboflavin in LEMONBOTTLE helps discharge dissolved fat from our body faster than normal metabolism speed. . . . Lecithin breaks down first cell fat membrane.”The website, www.sidmedicos.com, includes a link to the social media website for “Lemonbottleofficial,” www.instagram.com/lemonbottle_official, which includes the following:???? January 4, 2023 post: “NEW GAME CHANGER to lipolysis”???? October 15, 2024 post: “HEALTHY FAT LOSS TIPS You Need!”“LEMONBOTTLE for Stubborn fat.”???? July 30, 2024 post: “Target stubborn fat that exercise and diet alone can’t seem to eliminate . . . Struggling with stubborn fat that just won’t budge despite your best efforts? Discover a non-surgical alternative to liposuction that effectively targets and eliminates unwanted fat, giving you the body confidence you’ve been striving for . . . #lemonbottlefatdissolving.”???? July 18, 2024 post: “Are you bothered by belly fat that folds when you sit? Have your favorite pants suddenly become too snug? Trust LemonBottle to solve your stubborn fat concerns.”L-Carnitine Body Serum AmpouleFrom the product label???? “lipolytic solution”Matrigen PPC AmpouleFrom product label???? “Scientific lipolysis effects for balanced body lineBy applying PPC Ampoule into the fat tissues, it separates and destroys connection among fat cells around applied areas and decomposes fat. The decomposed fat is removed through body’s venous system and lymph system, because by this way PPC destroys applied area’s fat permanently, the treatment is also called ‘non-incision permanent fat removal treatment.”???? “PPC Ampoule Mechanism Diagram” accompanied by images of what appears to be the human abdominal area that reduces in size along with each the following stated steps:o “STEP 1 – Fat cells necessary to be treated on the body parts”o “STEP 2 – Apply PPC Ampoule and be delivered into targeted area”o “STEP 3 – Fat cells then separate and harden”o “STEP 4 – Harden fat cells break out and are excreted through the body”“LemonBottle Ampoule Solution,” “L-Carnitine Body Serum Ampoule,” and “Matrigen PPC Ampoule” are not generally recognized as safe and effective for the above referenced uses and, therefore, are “new drugs” under section 201(p) of the FD&C Act, 21 U.S.C. 321(p). Subject to certain exceptions not applicable here, new drugs may not be legally introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect, as described in sections 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(d) and 355(a). There are no FDA-approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, in effect for these products. Accordingly, the introduction or delivery for introduction into interstate commerce of these products violates sections 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(d) and 355(a).ConclusionThe violations cited in this letter are not intended to be an all-inclusive statement of past or present violations that may exist in connection with the products you distribute. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.This letter notifies you of our concerns and provides you an opportunity to address them. Failure to adequately address this matter may result in legal action including, without limitation, seizure and/or injunction. Please submit a written response to this letter within fifteen working days from the date of receipt, explaining the specific steps you have taken to address any violations. Include an explanation of each step being taken to prevent the recurrence of violations, including steps you will take to ensure that Amazon will no longer introduce, or deliver for introduction into interstate commerce unapproved injectable lipolytic drug products, as well as copies of related documentation. If you believe that the products you distribute are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration within fifteen working days from the date of receipt of this letter.Your response should be sent to U.S. Food and Drug Administration, CDER/OC/Office of Unapproved Drugs and Labeling Compliance by email to FDAADVISORY@fda.hhs.gov. Please include your firm name and the unique identifier “CMS 695821” in the subject line of the email.Sincerely,/S/Tina Smith, M.S.Captain, U.S. Public Health ServiceDirectorOffice of Unapproved Drugs and Labeling ComplianceOffice of ComplianceCenter for Drug Evaluation and ResearchFood and Drug Administration_________________1Amazon distributed each of the products directly to individual U.S. consumers on behalf of third parties. Each of the products discussed below was “fulfilled” by Amazon; your website states, “Fulfillment by Amazon (FBA) is a program that lets you outsource order fulfillment to Amazon and offer customers free, two-day shipping through Prime. By enrolling in FBA, you can send your products into Amazon’s global network of fulfillment centers, and we’ll pick, pack, and ship orders, as well as handle customer service and returns. FBA is part of a fully automated set of services we call Supply Chain by Amazon.” (See https://sell.amazon.com/fulfillment-by-amazon).

Delivery Method:Via EmailRecipient:Anakaren LopezC & A Naturistics2424 Hoover Ave, Ste NNational City,CA91950United Statesnaturisticsca@gmail.comIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWARNING LETTERMarch 4, 2025RE: 693439Dear Anakaren Lopez:This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your website at the Internet address https://www.productosnaturalesca.com from May 2024 to February 2025, and has observed that during this time your website offered the products “AK Forte,”1 “TE DE MORONEL,” “Jengibre en Polvo,” “Té Uva Ursi,” “RenaLimp,” “Miel de Abeja Para Limpiar tus Ojos,” and “Ojo Roja Para Limpiar tus Ojos” for sale in the United States. In addition, FDA has obtained a sample of your “AK Forte” product.As described below, these products are unapproved new drugs introduced or delivered for introduction into interstate commerce in violation of sections 505(a) and 301(d) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a) and 331(d). Furthermore, your “AK Forte,” “TE DE MORONEL,” “Jengibre en Polvo,” “Té Uva Ursi,” and “RenaLimp” products are misbranded drugs under section 502 of the FD&C Act, 21 U.S.C. 352, and introduced or delivered for introduction into interstate commerce in violation of section 301(a) of the FD&C Act, 21 U.S.C. 331(a). FDA confirmed through laboratory analysis that a sample of your “AK Forte” product contains the undeclared active pharmaceutical ingredients acetaminophen and diclofenac. Acetaminophen is a drug used to reduce pain and fever that is found in many prescription and over-the-counter drug products. Use of the product “AK Forte” poses a serious threat to consumers because it may result in unintentional acetaminophen overdose, especially if it is used in combination with other acetaminophen-containing products. Acetaminophen overdose can cause liver damage (hepatoxicity), ranging in severity from abnormalities in liver function to acute liver failure, and even death. People who experience unintentional acetaminophen overdose may not seek prompt medical attention because the symptoms of liver damage can take several days to emerge, even in severe cases. Acetaminophen may also cause serious skin reactions. Symptoms may include skin reddening, rash, and blisters.Diclofenac is a non-steroidal anti-inflammatory drug (NSAID). NSAIDs may cause increased risk of cardiovascular events, such as heart attack and stroke, as well as serious gastrointestinal damage, including bleeding, ulceration, and fatal perforation of the stomach and intestines. Diclofenac may also interact with other medications and significantly increase the risk of adverse events, particularly when consumers use multiple NSAID-containing products.Information on the label and/or labeling of your “AK Forte” product demonstrates that this product is marketed as a dietary supplement. However, under section 201(ff)(3)(B)(i) of the FD&C Act, 21 U.S.C. 321(ff)(3)(B)(i), a dietary supplement may not include an article that is approved as a new drug under section 505 of the FD&C Act unless that article was marketed as a dietary supplement or food before its approval as a drug. FDA approved diclofenac, under the trade name Voltaren, as a new drug on July 28, 1988. Given that diclofenac was not marketed as a dietary supplement or as food before Voltaren was approved, “AK Forte,” which contains diclofenac, is excluded from the definition of a dietary supplement under section 201(ff)(3)(B)(i) of the FD&C Act, 21 U.S.C. 321(ff)(3)(B)(i).Moreover, we note regardless of whether your “AK Forte” product is excluded from the definition of a dietary supplement, it is a drug under section 201(g)(1)(B) of the FD&C Act, 21 U.S.C. 321(g)(1)(B), because it is intended for, among other things, use as an arthritis treatment.We also note that your “Miel de Abeja Para Limpiar tus Ojos” and “Ojo Roja Para Limpiar tus Ojos” products are especially concerning from a public health perspective. Ophthalmic drug products, which are intended for administration into the eyes, in general pose a greater risk of harm to users because the route of administration for these products bypasses some of the body’s natural defenses.Unapproved New DrugsYour “AK Forte,” “TE DE MORONEL,” “Jengibre en Polvo,” “Té Uva Ursi,” “RenaLimp,” “Miel de Abeja Para Limpiar tus Ojos,” and “Ojo Roja Para Limpiar tus Ojos” products are drugs as defined by section 201(g)(1) of the FD&C Act 21, U.S.C. 321(g)(1) because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease and/or intended to affect the structure or any function of the body. Examples of claims observed on your website that provide evidence of the intended use of these products as drugs include, but may not be limited to, the following:AK ForteOn your webpage, https://www.productosnaturalesca.com/product-page/ak-forte-con-ortiga-yomega100tab:???? “Highly effective in cartilage reconstruction”???? “Fight Arthritis”???? “Stops the advance of breakdown in joints”???? “Anti-inflammatory and analgesic”???? “Effective in joint problems of sports lessons”???? “Improves mobility and normal joint function”TE DE MORONELOn your webpage, https://www.productosnaturalesca.com/product-page/moronel-te-100-calidad-la-plantade-la-vida-2oz-4oz-dist-by-aj-herbs:???? “Moronel is a medicinal plant that is used very effectively in the treatment of cancer, diabetes, cholesterol, blood pressure, prostatitis, arthritis, kidney problems, liver poisoning, among other diseases, in addition to naturally combating viruses and bacteria. [sic] & fungus.”Jengibre en PolvoOn your webpage, https://www.productosnaturalesca.com/product-page/jengibre-en-polvo-120-grs-ginger:???? “Assistant in: Gastritis . . . Nervous colitis . . . Colon Cancer”Té Uva UrsiOn your webpage, https://www.productosnaturalesca.com/product-page/uva-ursi-100-natural-no-caffeine:???? “It decreases the accumulation of uric acid and reduces the risk of developing kidney stones.”???? “It has antibacterial action against multiple bacteria such as Escherichia coli, staphylococci or pseudomonas, it also has antifungal activity against candida albicans.”???? “[U]va ursi is effective in the treatment of herpes, wounds and burns.”???? “[I]t is useful in the treatment of rheumatism and arthritis”RenaLimpOn your webpage, https://www.productosnaturalesca.com/product-page/renalimpc%C3%A1lculosrenales-piedras-en-los-ri%C3%B1ones:???? “RenaLimp Dissolves Kidney Stones”???? “Assist in the treatment for kidneys [sic] symptoms such as kidney pain, infections, stones or kidney stones.”Miel de Abeja Para Limpiar tus OjosOn your webpage, https://www.productosnaturalesca.com/product-page/gotas-miel-de-abeja-para-limpiartus-ojos-eye-drops:???? “HONEYBEETo Clean Your EyesNatural SolutionIndicated For:Conjunctivitis. . .Inflamed Eyelids. . .mild infections”Ojo Roja Para Limpiar tus OjosOn your webpage, https://www.productosnaturalesca.com/product-page/ojo-rojo-gotas-40ml:???? “Indicated For:Conjunctivitis. . .Inflamed Eyelidsmild infections”Your “AK Forte,” “TE DE MORONEL,” “Jengibre en Polvo,” “Té Uva Ursi,” “RenaLimp,” “Miel de Abeja Para Limpiar tus Ojos,” and “Ojo Roja Para Limpiar tus Ojos” products are not generally recognized as safe and effective for their above referenced uses and, therefore, are “new drugs” under section 201(p) of the FD&C Act, 21 U.S.C. 321(p). With certain exceptions not applicable here, a new drug may not be legally introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect, as described in sections 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(d) and 355(a). Because “AK Forte,” “TE DE MORONEL,” “Jengibre en Polvo,” “Té Uva Ursi,” “RenaLimp,” “Miel de Abeja Para Limpiar tus Ojos,” and “Ojo Roja Para Limpiar tus Ojos” are new drugs and there are no FDA-approved applications in effect for these products, these products are unapproved new drugs.Introduction or delivery of these unapproved new drug products into interstate commerce violates sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C. 355(a) and 331(d).Misbranded DrugsYour “AK Forte” product is misbranded under section 502(a) of the FD&C Act, 21 U.S.C. 352(a). Under section 502(a) of the FD&C Act, 21 U.S.C. 352(a), a drug is misbranded if its labeling is false or misleading in any particular. Section 201(n) of the FD&C Act, 21 U.S.C. 321(n), provides that, in determining whether an article’s labeling or advertising “is misleading there shall be taken into account . . . not only representations made or suggested . . . but also the extent to which the labeling or advertising fails to reveal facts material in light of such representations.” The labeling for your “AK Forte” product does not declare that the product contains acetaminophen or diclofenac. As previously mentioned, these undeclared ingredients in your “AK Forte” product may pose serious health risks because consumers with underlying medical issues may take the products without knowing that they can cause serious harm or interact in dangerous ways with other drugs they may be taking. The failure to disclose these ingredients in the product labeling renders your “AK Forte” product misbranded under section 502(a) of the FD&C Act, 21 U.S.C. 352(a).Additionally, a drug is misbranded under section 502(f)(1) of the FD&C Act, 21 U.S.C. 352(f)(1) if the drug fails to bear adequate directions for its intended use(s). “Adequate directions for use” means directions under which a layperson can use a drug safely and for the purposes for which it is intended (21 CFR 201.5). Prescription drugs, as defined in section 503(b)(1)(A) of the Act, 21 U.S.C. 353(b)(1)(A), can only be used safely at the direction, and under the supervision, of a licensed practitioner.Your “TE DE MORONEL,” “Jengibre en Polvo,” “Té Uva Ursi,” and “RenaLimp” products are intended for prevention or treatment of one or more diseases that are not amenable to self-diagnosis, prevention, or treatment without the supervision of a licensed practitioner. Therefore, it is impossible to write adequate directions for a layperson to use these products safely for their intended purposes. Accordingly, your “TE DE MORONEL,” “Jengibre en Polvo,” “Té Uva Ursi,” and “RenaLimp” products fail to bear adequate directions for their intended uses and, therefore, are misbranded under section 502(f)(1) of the Act, 21 U.S.C. 352(f)(1). The introduction or delivery for introduction into interstate commerce of these misbranded drug products is a prohibited act under section 301(a) of the FD&C Act, 21 U.S.C. 331(a).We also documented that your website https://productosnaturalesca.com offered for sale “Artri Ajo King,”2“Artri King,”3“Ortiga Mas Ajo,”4“RM Flex,”5Reumo Flex,”6and “Umary”7to consumers in the United States. Previous FDA lab analyses of products similarly named to those sold on your website revealed these products contained the undeclared drug ingredients. While the Agency has not sampled and tested these product variations from your inventory to date, this letter also expresses our serious concern about the safety of these products and emphasizes that it is your legal responsibility under federal law to ensure that products you sell do not contain any undeclared or potentially harmful ingredients, and that they are marketed in compliance with applicable laws.ConclusionThis letter is not intended to be an all-inclusive statement of violations that may exist in connection with your products. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.This letter notifies you of our concerns and provides you an opportunity to address them. Failure to adequately address this matter may result in legal action including, without limitation, seizure and/or injunction.Please notify FDA in writing, within fifteen working days of receipt of this letter, of the specific steps you have taken to correct any violations. Include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. 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. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the time within which you will complete the correction.Your response should be sent to U.S. Food and Drug Administration, CDER/OC/Office of Unapproved Drugs and Labeling Compliance by email to FDAAdvisory@fda.hhs.gov. Please include your firm name and the unique identifier “CMS 693439” in the subject line of the email.Sincerely,/S/Tina Smith, M.S.Captain, U.S. Public Health ServiceDirectorOffice of Unapproved Drugs and Labeling ComplianceOffice of ComplianceCenter for Drug Evaluation and ResearchU.S. Food and Drug Administration___________________1FDA issued a warning to consumers not to use your “AK Forte” product (see: https://www.fda.gov/drugs/medication-healthfraud/public-notification-ak-forte-contains-hidden-drug-ingredients). Further, we acknowledge that you recalled your “AK Forte” 400 mg tablets product in October 2024 due to the presence of undeclared Diclofenac, Dexamethasone, and Methocarbamol (see https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/ca-naturistics-issues-voluntary-nationwide-recall-ak-fortetablets-con-ortiga-y-omega-3-due-presence).2https://www.fda.gov/drugs/medication-health-fraud/public-notification-artri-ajo-king-contains-hidden-drug-ingredient3https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-consumers-not-purchase-or-use-artri-and-ortiga-productswhich-may-contain-hidden-drug4https://www.fda.gov/drugs/medication-health-fraud/public-notification-ortiga-mas-ajo-rey-contains-hidden-drug-ingredient5https://www.fda.gov/drugs/medication-health-fraud/public-notification-rmflex-contains-hidden-drug-ingredient6https://www.fda.gov/drugs/medication-health-fraud/reumo-flex-contains-hidden-drug-ingredient7https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-consumers-not-purchase-or-use-umary-and-amazy-productsthey-may-be-harmful-your-health

Delivery Method:VIA EMAIL CONFIRMED DELIVERYProduct:DrugsRecipient:Evan GilbertCEORight Value Drug Stores, LLC dba Carie Boyd Pharmaceuticals2501 W. Oak StreetDenton,TX76201United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWARNING LETTERWL # 69468712/17/2024Dear Mr. Gilbert:You registered your facility with the U.S. Food and Drug Administration (FDA) as an outsourcing facility under section 503B of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. § 353b]1on July 3, 2019, and most recently on December 12, 2023. From May 28, 2024, to June 21, 2024, an FDA investigator inspected your facility, Right Value Drug Stores, LLC dba Carie Boyd Pharmaceuticals, located at 8400 Esters Blvd, Suite 190, Irving, TX 75063. During the inspection, the investigator noted that drug products you produced failed to meet the conditions of section 503B of the FDCA necessary for drugs produced by an outsourcing facility to qualify for exemptions from certain provisions of the FDCA. In addition, the investigator noted serious deficiencies in your practices for producing drug products, which put patients at risk.FDA issued a Form FDA 483 to your facility on June 21, 2024. FDA acknowledges receipt of your facility’s response, dated July 15, 2024. Based on this inspection, it appears you produced drug products that violate the FDCA.A. Compounded Drug Products under the FDCAUnder section 503B(b) of the FDCA, a compounder can register as an outsourcing facility with FDA. Drug products compounded by or under the direct supervision of a licensed pharmacist in an outsourcing facility qualify for exemptions from the drug approval requirements in section 505 of the FDCA [21 U.S.C. § 355(a)], the requirement in section 502(f)(1) of the FDCA [21 U.S.C. § 352(f)(1)] that labeling bear adequate directions for use and the Drug Supply Chain Security Act requirements in section 582 of the FDCA [21 U.S.C. § 360eee-1] if the conditions in section 503B of the FDCA are met.2An outsourcing facility, which is defined in section 503B(d)(4) of the FDCA [21 U.S.C. § 353b(d)(4)], is a facility at one geographic location or address that — (i) is engaged in the compounding of sterile drugs; (ii) has elected to register as an outsourcing facility; and (iii) complies with all of the requirements of this section. Outsourcing facilities must comply with other applicable provisions of the FDCA, including section 501(a)(2)(B) [21 U.S.C. § 351(a)(2)(B)], regarding current good manufacturing practice (CGMP), and section 501(a)(2)(A) [21 U.S.C. § 351(a)(2)(A)], regarding insanitary conditions. Generally, CGMP requirements for the preparation of drug products are established in Title 21 of the Code of Federal Regulations (CFR) parts 210 and 211.For a compounded drug product to qualify for the exemptions under section 503B, the labeling of the drug must include certain information (section 503B(a)(10) of the FDCA [21 U.S.C. §353b(a)(10)]).B. Failure to Meet the Conditions of Section 503BDuring the inspection, the FDA investigator noted that drug products produced by your facility failed to meet the conditions of section 503B. For example, the investigator noted that some of your facility’s drug products, such as Ketoconazole 2%(b)(4)Cream, Testosterone Cypionate 200 mg/ml injections, and Testosterone Cypionate 200 mg/ml + Testosterone Propionate 10 mg/ml injections, did not include the following information on the label: The quantity or proportion of each inactive ingredient.Because your compounded drug products have not met all of the conditions of section 503B, they are not eligible for the exemptions in that section from the FDA approval requirements of section 505, the requirement under section 502(f)(1) that labeling bear adequate directions for use, and the Drug Supply Chain Security Act requirements described in section 582 of the FDCA.Specific violations are described below.C. Violations of the FDCAAdulterated Drug ProductsFDA investigator noted that drug products intended or expected to be sterile were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health, causing your drug products to be adulterated under section 501(a)(2)(A) of the FDCA. For example, the investigator observed:1. Your firm failed to perform adequate smoke studies under dynamic conditions to demonstrate unidirectional airflow within the ISO 5 area. Therefore, your products intended to be sterile are produced in an environment that may not provide adequate protection against the risk of contamination. Specifically, your smoke studies demonstrated disruption in unidirectional airflow in your BSC hood 19-00133.2. Your media fills were not performed under the most challenging or stressful conditions. Therefore, there is a lack of assurance that your firm can aseptically produce drug products within your facility. Specifically, your firm’s media fill vial quantity per technician fails to reflect the most challenging conditions.FDA investigator also noted CGMP violations at your facility, that caused your drug product(s) to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA. The violations include, for example:1. Your firm failed to follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)).2. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).3. Your firm failed to clean and sterilize and process, where indicated by the nature of the drug, container closures to remove pyrogenic properties to assure they are suitable for their intended use (21 CFR 211.94(c)).4. Your firm failed to establish and follow adequate written procedures for cleaning and maintenance of equipment (21 CFR 211.67(b)).5. Your firm failed to provide equipment for adequate control over air pressure, micro-organisms, dust, humidity, and temperature when appropriate for the manufacture, processing, packing, or holding of a drug product (21 CFR 211.46(b)).Outsourcing facilities must comply with CGMP requirements under section 501(a)(2)(B) of the FDCA. FDA’s regulations regarding CGMP requirements for the preparation of drug products have been established in 21 CFR parts 210 and 211. FDA intends to promulgate more specific CGMP regulations for outsourcing facilities. FDA has issued a revised draft guidance,Current Good Manufacturing Practice — Guidance for Human Drug Compounding Outsourcing Facilities under Section 503B of the FD&C Act.This draft guidance, when finalized, will describe FDA’s expectations regarding outsourcing facilities and the CGMP requirements in 21 CFR parts 210 and 211 until more specific CGMP regulations for outsourcing facilities are promulgated.Under section 301(a) of the FDCA [21 U.S.C. § 331(a)], the introduction or delivery for introduction into interstate commerce of any drug that is adulterated is a prohibited act. Further, it is a prohibited act under section 301(k) of the FDCA [21 U.S.C. § 331(k)] to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being adulterated.Unapproved New Drug ProductsYou do not have any FDA-approved applications on file for drug products that you compound.3Under sections 505(a) and 301(d) of the FDCA [21 U.S.C. §§ 331(d)] a new drug may not be introduced into or delivered for introduction into interstate commerce unless an application approved by FDA under section 505 of the FDCA is in effect for the drug. Marketing of these products, or other applicable products, without an approved application violates these provisions of the FDCA.Misbranded Drug ProductsYou compound drug products that are intended for conditions not amenable to self-diagnosis and treatment by individuals who are not medical practitioners; therefore, adequate directions for use cannot be written so that a layman can use these products safely for their intended uses. Consequently, their labeling fails to bear adequate directions for their intended uses causing them to be misbranded under section 502(f)(1) of the FDCA.4The introduction or delivery for introduction into interstate commerce of these products therefore violates section 301(a) of the FDCA. Further, it is also a prohibited act under section 301(k) of the FDCA to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being misbranded.D. Corrective ActionsWe have reviewed your facility’s responses to the Form FDA 483. Some of your corrective actions appear adequate; however, we are unable to fully evaluate some of your corrective actions due to lack of adequate supporting documentation:1. Regarding your firm’s failure to establish and follow adequate written procedures for cleaning and maintenance of equipment:a. We acknowledge that your staff were re-trained on the Cleaning and(b)(4)of Glassware SOP. In your response, you stated you are working on a Glassware Hold Study; however, we are unable to review the adequacy of your response until your hold studies are completed and submitted for review.2. Regarding your firm’s failure to provide equipment for adequate control over air pressure, micro-organisms, dust, humidity, and temperature when appropriate for the manufacture, processing, packing, or holding of a drug product:a. You stated you are purchasing additional equipment to control environmental variables, such as temperature and humidity in your DEA Lockup area, however, we are unable to review the adequacy of your response until you submit further details about your proposed corrective actions (e.g., implementation time frame, equipment qualification and written procedures, etc.).b. You stated that you intend to execute process validation for other product families stored in the Lockup area. However, details of your plan, such as the names of the other product families and how you plan to implement these validation protocols were not provided.Some of your corrective actions appear deficient:1. We acknowledge that on July 5, 2024, your firm re-executed smoke studies. Some of the smoke studies provided for review demonstrated non-unidirectional, recirculating airflow within the hood. For example, video 19-00133 Transfer of Vials into the Hood,(b)(4)currents were detected from time stamp 00:25 and could be identified throughout the video duration. Video 19-00133 EM Sampler Running and Filling of(b)(4)Vials,(b)(4)currents were identified from time stamp 12:07-12:17 and 13:20-14:54. In both videos, the disruption in airflow appeared to be in the far-right hand side of the BSC hood where empty vials were sitting. The ISO-5 area is critical because sterile drug products are exposed and therefore vulnerable to contamination. Your aseptic manufacturing process should be designed, and operations should be executed to minimize contamination hazards to your sterile drug product.2. Regarding your Aseptic Process Simulations, batch records reveal that each operator is required to fill a minimum of(b)(4)units, however, during production an operator can fill up to(b)(4)units. Gowned personnel are the greatest source of microbial contamination in an aseptic process. Operators performing a media fill of less than their typical production volume and duration does not represent the worst-case challenge and stressful condition as it does not take into regard operator fatigue. Your firm failed to provide a robust media fill that mimics an operator’s actual production activity.3. We acknowledge your initiation of deviations, DEV-2024-046 and DEV-2024-047 and investigation IR-2024-013 in relation to the power outage that occurred on 05/28/2024. However, utilizing visual inspection as your method in identifying the impact of humidity on your in-process pellets is inadequate. Your proposed method of visually inspecting pellets for “swelling” is not scientifically sound, nor data driven.4. Regarding DEV-2023-073 and DEV-2023-074 o, we acknowledge your firm performed an investigation regarding the Total Airborne Particles exceeding the ISO 5 specifications on 12/20/2023 during the filling of Testosterone Cypionate/Testosterone Propionate 200/10 mg/ml with Miglyol R 812N, Lot(b)(4). However, upon reviewing the production Batch Record(b)(4), it was noted there were 26 major defects identified during the visual inspection, including dark particulates and filaments in vials. Despite those vials being removed, it appears no further investigation occurred.5. Regarding the preparation of container closures to remove pyrogenic properties, your firm failed to adequately validate the(b)(4)process for your pellet vial caps and continued to use this process in the manufacturing of drug products. The process validation report, GS-2023-025 (dated 07/03/2023) cited multiple samples failing a(b)(4)in endotoxins. Your firm launched an investigation, IR-2023-036 (dated 09/06/2023) and it was concluded that the rinsing time needed to be increased and the process validation was to be repeated. It appears from your response and the documents provided, the process validation was never repeated. Additionally, your firm concluded the impact of endotoxin being present on a vial cap as low and stated in IR-2023-036, “there is minimal, if any, interaction/contact between the pellet within the vial and the cap,” and thus “there is no impact against any product which has or is being processed using caps that are processed by the current(b)(4)by rinsing procedure. There is no scientific basis for the justification of your claim.In addition to the issues discussed above, you should note that CGMP requires the implementation of quality oversight and controls over the manufacture of drugs, including the safety of raw materials, materials used in drug manufacturing, and finished drug products. See section 501 of the FDCA. If you choose to contract with a laboratory to perform some functions required by CGMP, it is essential that you select a qualified contractor and that you maintain sufficient oversight of the contractor’s operations to ensure that it is fully CGMP compliant. Regardless of whether you rely on a contract facility, you are responsible for assuring that drugs you produce are neither adulterated nor misbranded. See 21 CFR 210.1(b), 21 CFR 200.10(b).In addition, regarding observations related to the conditions of section 503B of the FDCA, your corrective actions appear adequate: you provided corrected labels that included the specific amounts of inactive ingredients or the quantity or proportion of each inactive ingredient.Should you continue to compound and distribute drug products that do not meet the conditions of section 503B, the compounding and distribution of your drugs would be subject to the new drug approval requirement, the requirement to label drug products with adequate directions for use, and the Drug Supply Chain Security Act requirements.FDA strongly recommends that your management undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance, materials, and systems. In particular, this review should assess your aseptic processing operations. A third party consultant with relevant sterile drug manufacturing expertise should assist you in conducting this comprehensive evaluation.E. ConclusionThe violations cited in this letter are not intended to be an all-inclusive statement of violations at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.You should take prompt action to address any violations. Failure to adequately address any violations may result in legal action without further notice, including, without limitation, seizure and injunction.Within fifteen (15) working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to address any violations. Please include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. This letter notifies you of our concerns and provides you an opportunity to address them. If you believe your products are not in violation of the FDCA, include your reasoning and any supporting information for our consideration. If you cannot completely address this matter within fifteen (15) working days, state the reason for the delay and the time within which you will do so.Your response and any questions regarding the contents of this letter should be sent to compoundinginspections@fda.hhs.gov. In your response, refer to the Warning Letter Number above (WL # 694687) and include a subject line that clearly identifies the submission as a Response to Warning Letter.Sincerely,/S/F. Gail Bormel, JD, RPhDirectorOffice of Compounding Quality and ComplianceOffice of ComplianceCenter for Drug Evaluation and Research_______________________1See Pub. L. No. 113-54, § 102(a), 127 Stat. 587, 587-588 (2013).2We remind you that there are conditions, other than those discussed in this letter, that must be satisfied to qualify for the exemptions in section 503B of the FDCA.3The specific products made by your firm are drugs within the meaning of section 201(g) of the FDCA [21 U.S.C. § 321(g)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of diseases and/or because they are intended to affect the structure or any function of the body. Further, they are “new drugs” within the meaning of section 201(p) of the FDCA [21 U.S.C. § 321(p)] because they are not generally recognized as safe and effective for their labeled uses.4Your compounded drug products are not exempted from the requirements of section 502(f)(1) of the FDCA by regulations issued by the FDA (see, e.g., 21 CFR 201.115).

Delivery Method:Via EmailReference #:320-25-47Product:DrugsRecipient:Changhui QiLinghai ZhanWang Biotechnology Co., LtdNo. 7-2, Dalinghe Industrial ParkLinghai ShiJinzhou ShiLiaoning Sheng,121200ChinaIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-47February 25, 2025Dear Changhui Qi:Your facility is registered with the United States Food and Drug Administration (FDA) as a manufacturer of over-the-counter (OTC) drug products. FDA has reviewed the records you submitted in response to our February 26, 2024 request, and subsequent correspondence, for records and other information pursuant to section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) for your facility, Linghai ZhanWang Biotechnology Co., Ltd, FEI 3015248821, at No. 7-2, Dalinghe Industrial Park, Linghai, Jinzhou, Liaoning 121200, China.This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding of drugs as described in your response to our 704(a)(4) request do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 351(a)(2)(B)).Following review of records and other information provided pursuant to section 704(a)(4) of the FD&C Act, significant violations were observed including, but not limited to, the following:1. Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality (21 CFR 211.84(d)(1) and 211.84(d)(2)).Your firm manufactured OTC drug products, including anti-microbial wipes. Based on the records and information you provided, you did not demonstrate that you are adequately testing the identity of components used in the manufacture of your drug products. For example, you did not test your active ingredient, ethanol, for methanol content.Additionally, you did not demonstrate the purity and quality of the components used in the manufacture of your drug products. For example, you did not test your glycerin and(b)(4)components for the presence of diethylene glycol (DEG) and ethylene glycol (EG).Component testing is fundamental to quality. Without adequate testing you do not have scientific evidence that your raw materials conform to appropriate specifications prior to use in the manufacture of your drug products. As a manufacturer, you have a responsibility to sample, test, and examine drug components before use in production to assure adequate quality.The use of ethanol contaminated with methanol has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document,Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol, at https://www.fda.gov/media/173005/download.The use of ingredients contaminated with DEG or EG has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance documentTesting of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycolto help you meet the CGMP requirements when manufacturing drugs containing ingredients at high-risk for DEG or EG contamination at https://www.fda.gov/media/167974/download.2. Your firm failed to establish an adequate written testing program designed to assess the stability characteristics of drug products and to use results of stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).The records and information you provided did not demonstrate that your firm has an adequate stability program for the OTC anti-microbial wipes you manufacture. For example, you conducted stability studies under “accelerated aging experiments” for your anti-microbial wipes without scientific justification. These experiments were conducted over a(b)(4)period at(b)(4)°C and 75% relative humidity. In addition, you did not perform stability studies under long-term storage conditions to support the(b)(4)expiration date on the label.Without appropriate stability studies, you do not have scientific evidence to support whether your drug products meet established specifications and retain their quality attributes through their labeled expiry.3. Your firm failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products (21 CFR 211.22(a)).The records and information you provided demonstrate that your quality unit (QU) did not effectively exercise its responsibilities to oversee the quality of your OTC drug manufacturing operations. Your QU is responsible for fully exercising its authority and responsibilities. FDA is concerned that your QU may not be conducting appropriate oversight regarding drug CGMP operations.See FDA’s guidance documentQuality Systems Approach to Pharmaceutical CGMP Regulationsfor help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211 at https://www.fda.gov/media/71023/download.ConclusionThe violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.FDA placed all drugs and drug products offered for import into the United States from your firm on Import Alert 66-40 on February 10, 2025.Correct any violations promptly. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may inspect to verify that you have completed corrective actions to any violations.Failure to address any violations may also result in the FDA continuing to refuse admission of articles manufactured at Linghai ZhanWang Biotechnology Co., Ltd, FEI 3015248821, located at No. 7-2, Dalinghe Industrial Park, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated may be detained or refused admission.This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3015248821 and ATTN: Carrie Hughes.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research

Delivery Method:VIA Electronic MailReference #:320-25-49Product:DrugsRecipient:Mr. V. Vishnu Murthy RajuManaging DirectorShree Jaya Laboratories PVT. LTD.Plot No. 11, Road No. 3, ALEAP Industrial EstateNear Pragathi Nagar, Kukatpally Hyderabad500090IndiaIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-49February 28, 2025Dear Mr. Raju:The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Shree Jaya Laboratories PVT. LTD., FEI 3011845012, at Sy. No. 299, Malkapur Village and Post, Choutuppal Mandal, Yadadri Bhuvanagiri District, Telangana from September 4 to 12, 2024.This warning letter summarizes significant deviations from Current Good Manufacturing Practice (CGMP) for active pharmaceutical ingredients (APIs).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your APIs are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).We reviewed your October 1, 2024 response to our Form FDA 483 in detail.During our inspection, our investigators observed specific deviations including, but not limited to, the following.1. Failure to clean equipment and utensils to prevent contamination or carry-over of a material that would alter the quality of the intermediates beyond the official or other established specifications.You failed to have adequate procedures for the cleaning and maintenance of manufacturing equipment and facilities. Our inspection found manufacturing equipment labeled as “Cleaned” and found the following deficiencies. For example:•(b)(4)#B-(b)(4)-404 in Production Block-(b)(4)was documented on the equipment usage log as “Cleaned as per SOP” on September 5, 2024; however, excessive(b)(4)colored residues were observed inside the(b)(4)later this same day. This(b)(4)is used to manufacture(b)(4).•(b)(4)#BI/(b)(4)in Room #(b)(4)used to manufacture(b)(4)intermediate, was documented on the equipment usage log as “Cleaned as per SOP” on August 30, 2024; however,(b)(4)was observed on the inside and outside of the equipment’s product discharge area.In addition, buildings used in the manufacture of key starting materials and intermediates used in the production of APIs are not maintained in a good state of repair. For example, the ceiling above(b)(4)located outside Production Block-(b)(4)was observed to be heavily stained, and with cracks and fallen plaster. These(b)(4)are used to manufacture(b)(4).In your response, you state that the equipment used in the(b)(4)processing areas is dedicated and the(b)(4)found on the equipment surfaces corresponds to the same compound, therefore, no cross-contamination is expected. You acknowledge there was insufficient oversight in ensuring compliance with cleaning procedures and inadequate monitoring of cleaning intervals. In addition, you state that daily sanitation procedures were not adequately enforced to prevent material accumulation, but they will be reinforced. You also state that an immediate corrective action was to repair and restore the ceiling outside Production Block-(b)(4).Your response is inadequate. Although you indicate cross-contamination may not be expected, product carryover and unknown impurities may form as a result of product build up on unclean equipment. You also do not acknowledge why personnel signed off on equipment usage logs as equipment being clean when it was not clean. In addition, no evidence of the ceiling repair was provided.In response to this letter, provide the following:A comprehensive, independent retrospective assessment of your cleaning effectiveness to evaluate the scope of cross-contamination hazards. Include the identity of residues, other manufacturing equipment that may have been improperly cleaned, and an assessment whether cross-contaminated products may have been released for distribution. The assessment should identify any inadequacies of cleaning procedures and practices, and encompass each piece of manufacturing equipment used to manufacture more than one product.A corrective action and preventive action (CAPA) plan, based on the retrospective assessment of your cleaning program, that includes appropriate remediations to your cleaning processes and practices, and timelines for completion. Provide a detailed summary of vulnerabilities in your process for lifecycle management of equipment cleaning. Describe improvements to your cleaning program, including enhancements to cleaning effectiveness; improved ongoing verification of proper cleaning execution for all products and equipment; and all other needed remediations.2. Failure of your quality unit to ensure that quality-related complaints are investigated and resolved.You failed to adequately investigate a complaint of(b)(4)particles in the intermediate,(b)(4), Stage-(b)(4), batch(b)(4). The root cause was attributed to improper cleaning/usage of the(b)(4)bag. A CAPA to change the(b)(4)bag more frequently (i.e., after(b)(4)batches instead of(b)(4)batches) was proposed.The complaint investigation was deficient because it did not extend to other batches, as required by your procedure, and it failed to identify other potential causes of the(b)(4)particles. Despite CAPA implementation of more frequent(b)(4)bag changes, the(b)(4)in Production Block –(b)(4)was observed during the inspection to be in disrepair, with the interior lining worn and corroded. The(b)(4)is located outdoors, exposed to the outside environment, and was also observed to contain heavy rust and a dead insect. Your management acknowledged the condition of the equipment and environmental conditions were not evaluated as potential source(s) of the contamination.In your response, you acknowledge your procedure for handling complaint investigations, but did not account for environmental conditions, which likely contributed to the complaint. You provided an addendum investigation report extending the investigation to other batches and including environmental conditions. You also state that the(b)(4)equipment will be upgraded and enclosed to create a controlled environment.Your response is inadequate. You do not commit to conduct a retrospective review of all complaints to ensure they were adequately investigated, extended to other batches, and considered environmental conditions, if necessary.In response to this letter, provide a comprehensive assessment of your overall system for investigating deviations, discrepancies, complaints, out-of-specification results, and failures. Provide a detailed action plan to remediate this system. Your action plan should include, but not be limited to, significant improvements in investigation competencies, scope determination, root cause evaluation, CAPA effectiveness, quality unit oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.3. Failure of your quality unit to exercise its responsibility to ensure the intermediates manufactured at your facility are in compliance with CGMP.Several original batch production records were found torn in your scrapyard. The investigator asked to review the batch records associated with the torn documents. Your management then provided a second set of these batch records in question. During the inspection, no explanation was provided regarding how there could be two sets of original batch production records or who authorized the disposition of these documents.In addition, batch production records are not completed contemporaneously. Batch records were observed to be stored in the Quality Assurance (QA) department while manufacturing operations were ongoing. Production tasks performed by operators were recorded later by the production supervisor, who was overseeing five production rooms at the same time.In your response, you state that some of the batch production record pages were damaged by chemical spillages and the pages were replaced by the QA department. The damaged pages werenot returned to QA and were sent to the scrapyard. You explain that your production supervisor fills out the batch production records because your operators lack proficiency in English. You also state that several production staff members were unable to attend work due to illness, which is why one production supervisor had to oversee and record operations in multiple areas.Your response is inadequate. You failed to provide supporting evidence of any incident or deviation regarding chemical spills on CGMP documents. You also do not address your practice of tearing CGMP documents and its potential impact, including ensuring accurate results were reported when the batch production records were recreated. In addition, there is no assurance that CGMP activities are adequately performed and documented, given that the records are not in a language understood by your employees executing such activities.Complete and accurate batch production and control records must be contemporaneously documented to ensure that manufacturing processes are consistently followed and reproducible. Additionally, incomplete manufacturing records deprive you of the ability to adequately investigate deviations.Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture. See FDA’s guidance documentData Integrity and Compliance With Drug CGMPfor guidance on establishing and following CGMP compliant data integrity practices athttps://www.fda.gov/media/119267/download.In response to this letter provide a current risk assessment of the potential effects of the observed failures on the quality of your drugs. Your assessment should include analyses of the risks to patients caused by the release of drugs affected by a lapse of data integrity and analyses of the risks posed by ongoing operations.Additional API and Intermediate CGMP GuidanceFDA considers the expectations outlined in ICH Q7 when determining whether APIs and intermediates are manufactured in conformance with CGMP. See FDA’s guidance documentQ7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredientsfor guidance regarding CGMP for the manufacture of APIs and intermediates at https://www.fda.gov/files/drugs/published/Q7-Good-Manufacturing-Practice-Guidance-for-Active-Pharmaceutical-Ingredients-Guidance-for-Industry.pdf.ConclusionThe deviations cited in this letter are not intended to be an all-inclusive list of deviations that exist at your facility. You are responsible for investigating and determining the causes of any deviations and for preventing their recurrence or the occurrence of other deviations.If you are considering an action that is likely to lead to a disruption in the supply of drugs produced at your facility, FDA requests that you contact CDER’s Drug Shortages Staff immediately, at drugshortages@fda.hhs.gov, so that FDA can work with you on the most effective way to bring your operations into compliance with the law. Contacting the Drug Shortages Staff also allows you to meet any obligations you may have to report discontinuances or interruptions in your drug manufacture under 21 U.S.C. 356C(b). This also allows FDA to consider, as soon as possible, what actions, if any, may be needed to avoid shortages and protect the health of patients who depend on your products.Correct any deviations promptly. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any deviations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to any deviations.Failure to address any deviations may also result in the FDA refusing admission of articles manufactured at Shree Jaya Laboratories PVT. LTD., at Sy. No. 299, Malkapur Village and Post, Choutuppal Mandal, Yadadri Bhuvanagiri District, Telangana, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated may be detained or refused admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days1. Specify what you have done to address any deviations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3011845012 and ATTN: Emily Stoklosa.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research__________________1Under program enhancements for the Generic Drug User Fee Amendments (GDUFA) reauthorization for fiscal years (FYs) 2023-2027, also known as the GDUFA III Commitment Letter, your facility may be eligible for a Post-Warning Letter Meeting to obtain preliminary feedback from FDA on the adequacy and completeness of your corrective action plans.

Delivery Method:VIA Electronic MailProduct:Medical DevicesRecipient:Jodie C. FamChief Executive OfficerQ’Apel Medical, Inc.4245 Technology DriveFremont,CA94538United StatesIssuing Office:Center for Devices and Radiological HealthUnited StatesWARNING LETTERFebruary 5, 2025Dear Ms. Fam:During an inspection of your firm located in Fremont, CA on July 29, 2024, through August 8, 2024, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufactures the 072 Aspiration System (also marketed under the trade name “HIPPO”). Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 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.FDA has reviewed information collected during the inspection of your firm located in Fremont, California on July 29, 2024, through August 8, 2024, and determined that the 072 Aspiration System (HIPPO) is adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. §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. § 360e(a), or an approved application for an investigational device exemption (IDE) under section 520(g) of the Act, 21 U.S.C. § 360j(g), for the device as described and marketed. The device is also misbranded under section 502(o) the Act, 21 U.S.C. § 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.Specifically, FDA cleared, under K222786, the device that you identified in your submission to the agency as the 072 Aspiration System with the following indications, “072 Aspiration Catheter: As part of the 072 Aspiration System, the 072 Aspiration Catheter with a compatible suction pump is indicated for use in the revascularization of patients with acute ischemic stroke secondary to intracranial large vessel occlusive disease (within the internal carotid, middle cerebral - M1 and M2 segments, basilar, and vertebral arteries) within 8 hours of symptom onset. Patients who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who failed IV t-PA therapy are candidates for treatment. Aspiration Tubing: As part of the 072 Aspiration System, the Aspiration Tubing is intended to connect the 072 Aspiration Catheter to a compatible suction pump.” The 072 Aspiration System that was presented to us was cleared under K222786 with a design that included a catheter shaft with an inner diameter of 0.072 inch and an outer diameter of 0.0855 inch for the entire catheter working length. The submission that we numbered K222786 did not describe technological characteristics of the distal nitinol tip that would enable expansion of the distal tip to larger diameters or compression of the distal tip during clinical use. However, your firm’s promotion of the device and information collected during the inspection provides evidence that the device as it was designed and developed but not described in your submission includes a nitinol tip with technological characteristics that allow for expansion in diameter and compression in length, i.e., a device for which your firm lacks clearance or approval. Examples of the promotion and information include:(b)(4)data report of tip compression testing (“Hippo Tip Vacuum Ball Testing”) was shared via emails exchanged within Q’Apel Medical(b)(4). The data include tip diameter and length measurements of multiple catheter tips (“bad units” and “good units”) while vacuum was applied to a(b)(4)ball with a diameter larger than the HIPPO distal tip diameter. Multiple images show increased diameters of the distal region of the nitinol tip expanding around the surface of the(b)(4)ball with reported increases in diameters of(b)(4)for “good units” and increases in diameter of(b)(4)for “bad units.” The(b)(4)data reports tip diameters ranging from(b)(4)inch with aspiration applied to the(b)(4)ball, compared to the relaxed tip diameter of(b)(4)inch to(b)(4)inch. The(b)(4)data reports accompanying changes in tip length of(b)(4)(relaxed tip lengths of(b)(4)inch, compressed under ball aspiration to lengths of(b)(4)inch) for “good units” and(b)(4)(relaxed tip lengths of(b)(4)inch, compressed under ball aspiration to lengths of(b)(4)inch) for “bad units.” The distinction of “good units” and “bad units” is not described in the(b)(4)data. However, both “good units” and “bad units” describe evidence of increased HIPPO distal tip diameters and compressed tip lengths when aspiration was applied to the(b)(4)balls. The submission K222786 did not provide images or information to show expansion of the distal tantalum markers or compression of tip length of the nitinol tip as shown in the images included in the(b)(4)data of tip compression testing (“Hippo Tip Vacuum Ball Testing”).The “(b)(4)” includes a video on page 35 of 45 titled “Mechanism of action,” that shows the nitinol tip of the HIPPO catheter aspirating a simulated clot. The video shows the catheter tip compress near the mid-point of the nitinol tip structure (with possible increased diameter), while the distal tantalum petal markers are obscured by the simulated clot. A second distinct slow-motion video also titled, “Mechanism of action,” is included on page 36 of 45 of the “(b)(4)” that shows the nitinol tip of the HIPPO catheter aspirating a simulated clot. This video shows the HIPPO catheter tip prior to contact with the simulated clot and upon contact with the simulated clot, the distal tantalum petal markers on the most distal struts of the nitinol tip are shown to flare at the edges combined with longitudinal compression of the nitinol tip while aspiration is applied to the clot until the clot is fully ingested through the catheter lumen. Page 37 of 45 of the “(b)(4)” includes a slow-motion video titled, “Mechanism of action: RED 72,” that shows aspiration of simulated clot with the cleared RED 72 Reperfusion Catheter (K211654) that was cited as a reference device during review of K222786 for the 072 Aspiration System (HIPPO). The video of the RED 72 Reperfusion Catheter does not show compression of the catheter tip or expansion of the distal catheter tip as observed in the videos of the HIPPO device on pages 35 and 36 of 45 of the “(b)(4).” Page 45 of 45 of the “(b)(4)” also includes a claim that the HIPPO provides “insightful navigation from a tip that flexes to any clot morphology.” The submission K222786 of the 072 Aspiration System (HIPPO) did not provide images that showed compression of the nitinol tip nor flaring of the distal petals of the nitinol tip as shown in videos presented in the “(b)(4).”• Drawing CS00788, “072 Catheter Nitinol Tip,” descriptions in the “Design History” notes that revision E updates included, “(b)(4).” The version of the drawing provided in K222786/S001, Appendix 27, was revision D and did not include descriptions of(b)(4)specification changes or “(b)(4)compression testing with tip compression tool.” The “(b)(4), CS 00788 Catheter Nitinol Tip,” document number QI 01560 describes(b)(4). The images and test methods for compression of the nitinol tip were not described in drawing CS00788, revision D, provided in K222786. The submission K222786 otherwise did not provide images that showed compression of the nitinol tip as described in document QI 01560.During review of K222786, FDA asked for a description of the principle of operation and mechanism of action of the 072 Aspiration Catheter distal tip, including the tip dimensions related to the dimensions of the remainder of the catheter shaft, in the Refuse-to-Accept (RTA) notification dated September 30, 2022. The response provided in the document “002_Cover Letter_RTA_Final.pdf” of the K222786/S001 submission dated October 24, 2022, stated that the 072 Aspiration Catheter tip had “the same Internal (0.072”) and External (0.0855”) dimensions (ID, OD) as the rest of the catheter’s usable length. The length of the tip is(b)(4)”. The flexible tip is a passive structure that does not have an active mechanism of action and is not self-expanding.” The information gathered in the inspection conducted July 29, 2024, through August 8, 2024, at your firm raises concerns that the information provided to FDA for review in K222786 did not accurately disclose the technological characteristics of the nitinol tip and the changes in diameter and length of the distal tip that could be exhibited during use conditions for aspiration of thrombus from patients experiencing acute ischemic stroke. These different technological characteristics of the nitinol tip to change in length and diameter constitute a change or modification in the device that could significantly affect the safety or effectiveness of the device (e.g., a significant change or modification in design, material, chemical composition, energy source, or manufacturing process) (21 CFR 807.81(a)(3)).For a device requiring premarket approval, the notification required by section 510(k) of the Act, 21 U.S.C. § 360(k), is deemed satisfied when a PMA is pending before the FDA. See 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.Our office requests that Q’Apel Medical cease any activities that result in the misbranding or adulteration of the 072 Aspiration System (HIPPO), such as the commercial distribution of the device for the uses discussed above.This inspection also revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. § 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.We received response from Jim Talbot, Vice President Regulatory, Quality, and Clinical Affairs dated August 28, 2024, September 26, 2024, and November 27, 2024, 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 document design input requirements as required by 21 CFR 820.30(c).For example, your firm did not adequately define the physical, performance, and other design requirements for design inputs to include tip compression, aspiration/suction pump, tip deflection, and treatment location for your firm’s 072 Aspiration System (Hippo), which are identified in your documents titled, Product Specification 072 Aspiration System (PS 00922, Rev. G) and Customer Requirement Specification Form (CRS 00848, Rev. D).We reviewed your firm’s response and conclude that it is not adequate. Your firm has not adequately defined specifications for tip elongation and compression (PS-11.5.2), aspiration flow rate (PS-11.5.3) and tip deflection (PS-11.5.9) that are identified in your document titled, Product Specification, PS 00922, Revision H.Your firm provided the document titled, Draft Research Report, Aspiration System, Aspiration Flowrate Acceptance Criteria, RR 02139, in your response dated August 28, 2024. This document appears to leverage previous testing of the Aspiration flowrate to define measurable acceptance criteria for future Aspiration Flowrate testing. The comparative device testing was conducted on a sample size of three(b)(4). The conclusion states an acceptance interval for the average flow rate is(b)(4). This value was not reflected in your Product Specification documentation or the Test Protocol, TP 00927, which is to be executed for future verification testing by a third-party service provider. It is not clear what this data will be used for.Please evaluate the adequacy of your corrective actions related to design inputs and continue to provide us information related to your ongoing corrective actions.2. Failure to adequately establish and maintain procedures for design verification as required by 21 CFR 820.30(f).For example, your firm did not adequately define acceptance criteria that can be verified for Aspiration Flowrate, Tip Deflection, and Tip Compression and Elongation in your protocol titled, Test Protocol, Device Performance Design Verification Validation, FG 00806, FG 00995 (TP 00927, Rev. C).Additionally, the verification test performed for Aspiration Flowrate and documented in Test Report 072 Aspiration System, Design Verification Validation, FG00806, FG 00995, Aspiration Flowrate (TR 00927-15, Rev. A), was conducted using(b)(4)vacuum setting, whereas the Instructions for Use for the device describes(b)(4)vacuum settings the device can be used with. There is no documented rationale to justify why testing flowrate at(b)(4)setting is adequate.We reviewed your firm’s response and conclude that it is not adequate. Your firm still has not implemented your design control procedure, in that your design verification protocol continues to not establish acceptance criteria for specifications to include tip deflection, elongation and compression, and aspiration flow rate that can be verified. Additionally, your firm’s rationale for testing a(b)(4)vacuum pressure is inadequate. Verification testing should be performed for all(b)(4)ranges utilized by the device.Your firm stated that you are(b)(4). However, the Test Report has not been provided to FDA.Please evaluate the adequacy of your corrective actions related to design verification and continue to provide us information related to your ongoing corrective actions.3. Failure to adequately establish and maintain procedures for design change as required by 21 CFR 820.30(i).For example, your firm has not implemented your procedure for design changes titled, Design Control (SOP 00003, Rev. C, effective date 02/01/2021 & Rev. D, effective date 11/14/2022) (revisions in effect when design changes were processed), which states that design changes are subject to original verification or validation tests and if no test(s) or a subset is planned, a justification is required. Specifically, your firm has not evaluated the impact changes may have to original verification or validation tests or provided a justification if no test(s) or a subset is required. Design changes were made to update the specification for your 072 Cather, Nitinol Tip(b)(4)(under ECO 1142) and to update the(b)(4)specification (under ECO 1360)(b)(4)acceptability range(b)(4). No assessment was documented of the potential impact the changes could have on completed verification and/or validation tests.We reviewed your firm’s response and conclude that it is not adequate. Your firm’s reevaluation of ECO 1360 states that the firm’s risk management document, RM 00951, Design FMEA, 072 Aspiration System, was updated in ECO 1300 to capture the new risk identified with SA 00570(b)(4). It further states that testing was performed via(b)(4). Your firm determined that verification and/or validation testing was not required. This assessment is inadequate. Testing should be documented and performed according to a defined protocol.Please evaluate the adequacy of your corrective actions related to design changes and continue to provide us information related to your ongoing corrective actions.4. Failure to adequately establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit as required by 21 CFR 820.198(a).For example, your firm has not adequately implemented your complaint procedure, Complaint Handling and Customer Feedback (SOP 00148, Rev. M, effective date 02/27/2024), which requires returned product analysis to be completed within 30 days after receiving the product from the field. Specifically,CN 0251 was opened to document a complaint reporting resistance was felt while the Hippo 072 Aspiration Catheter was inside an access catheter. The associated complaint product was received by your firm on 06/12/2024 under RMA0494 and logged in RMA log. As of 08/02/2024 the complaint product has not been investigated.CN 0252 was opened to document a complaint reporting stretching on the distal portion of the 072 Aspiration Tubing. The associated complaint product was received by your firm on 06/27/2024 under RMA0493 and logged in RMA log. As of 08/02/2024 the complaint product has not been investigated.We reviewed your firm’s response and conclude that it is not adequate. Removing the 30-day timeframe for completing the returned product analysis may impact your firm’s assessment of complaints that are determined to be malfunctions and thus your firm’s adherence to reporting timeframes required as part of the Medical Device Reporting (MDR) Regulation (see 21 CFR Part 803). Your firm should provide a risk-based justification for the removal of the requirement and evaluate complaints to determine if any unreported MDRs were found.5. Failure to adequately establish and maintain procedures for document control as required by 21 CFR 820.40.For example, your firm did not adequately implement your document control procedures as outlined in(b)(4)(SOP 00002, Rev. R, effective date 05/24/2024 (current revision), Rev. P, effective date 02/02/2024, and Rev. N, effective date 07/14/2023. Section 6.1 of your procedure titled(b)(4)(SOP 00460, Rev, A, effective date 9/14/2020)(b)(4). Specifically, the following promotional material for the 072 Aspiration System (Hippo) was not developed and approved per the firm’s document control procedures:A video clip depicting the tip of the Hippo aspiration catheter flaring outA video clip referring the to the Hippo aspiration catheter tip as adaptive, depicting the tip of the Hippo aspiration catheter flaring out, and referencing R&D Aspiration Grip Force dataA press release announcing the clearance of the Hippo 072 Aspiration System that describes the aspiration tip as adaptiveWe reviewed your firm’s response and cannot determine the adequacy at this time. Your firm extended the target completion date to 11/25/2025, for compiling of a list of marketing/ promotional content for their Armadillo and Walrus devices and evaluating if product claims were found.(b)(4); therefore, we request that you continue to provide information related to the(b)(4).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 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 e-mail to: Jessica Mu, Assistant Director at CDRHWarningLetterResponses@fda.hhs.gov. Refer to the Unique Identification Number,CMS # 699244, when replying. If you have any questions about the contents of this letter, please contact: Shaquenta Perkins at shaquenta.perkins@fda.hhs.gov or 619-941-3763.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 yours,/S/RDML Sean M. Boyd, MPH, USPHSDirectorOffice of Regulatory ProgramsOffice of Product Evaluation and QualityCenter for Devices and Radiological Health