

#### [63] nuvo-life-health-inc-dba-nuvo-life-health-715794-09092025 | issued 09/09/2025 | Nuvo Life Health Inc. dba Nuvo Life Health | SUBJ: Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the Internet (Telehealth)
WARNING LETTER September 9, 2025 Nuvo Life Health: This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your website content at the internet address https://nuvolifehealth.com in August 2025 and has observed that your website offers various compounded drug products, including semaglutide and tirzepatide. [B47] [B14] [B12] The following claims concerning compounded semaglutide and tirzepatide products appear on your website: • “Semaglutide Injection (similar to Ozempic and Wegovy)” • “Tirzepatide (similar to Mounjaro)” Compounded drug products are not FDA-approved. [B24] [B15] [B11] [B23] [B43] [B9] [B10] [B2] [B3] [B19] [B1] [B8] [B17] [B0] [B16] [B4] [B13] [B21] [B7] [B6] Sincerely, /s/ George Tidmarsh, M.D., Ph.D. [B18] [B92] [B5] [B22] Content current as of: 09/16/2025 Regulated Product(s)

#### [64] remedy-meds-716830-09092025 | issued 09/09/2025 | Remedy Meds | SUBJ: Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the Internet (Telehealth)
WARNING LETTER September 9, 2025 Remedy Meds: This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your website content at the internet address https://remedymeds.com in August 2025 and has observed that your website offers various compounded drug products, including semaglutide and tirzepatide. [B47] [B14] [B12] [B74] “Semaglutide (Compounded) Same active ingredient as Ozempic and Wegovy” “Tirzepatide (Compounded) Same active ingredient as Mounjaro and Zepbound” Compounded drug products are not FDA-approved. [B24] [B15] [B11] [B23] [B43] [B9] [B10] [B2] [B3] [B19] [B1] [B8] [B17] [B0] [B16] [B4] [B13] [B21] [B7] [B6] Sincerely, /S/ George Tidmarsh, M.D., Ph.D. [B18] Food and Drug Administration _____________________________ 1 The semaglutide and tirzepatide products offered on your website 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. [B5] [B22] Content current as of: 09/16/2025 Regulated Product(s)

#### [65] reset-iv-llc-dba-reset-iv-716488-09092025 | issued 09/09/2025 | Reset IV, LLC dba Reset IV | SUBJ: Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the Internet (Telehealth)
WARNING LETTER September 9, 2025 Reset IV: This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your website content at the internet address https://resetiv.com in August 2025 and has observed that your website offers various compounded drug products, including semaglutide and tirzepatide. [B47] [B14] [B12] [B74] “Semaglutide (the same ingredient in Wegovy & Ozempic)” “Tirzepatide (the same ingredient in Zepbound & Mounjaro)” Compounded drug products are not FDA-approved. [B24] [B15] [B11] [B23] [B43] [B9] [B10] [B2] [B3] [B19] [B1] [B8] [B17] [B0] [B16] [B4] [B13] [B21] [B7] [B6] Sincerely, /S/ George Tidmarsh, M.D., Ph.D. [B18] Food and Drug Administration _______________________ 1 The semaglutide and tirzepatide products offered on your website 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. [B5] [B22] Content current as of: 09/16/2025 Regulated Product(s)

#### [66] semabio-715866-09092025 | issued 09/09/2025 | SemaBio | SUBJ: Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the Internet (Telehealth)
WARNING LETTER September 9, 2025 SemaBio: This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your website content at the internet address https://sema.bio in August 2025 and has observed that your website offers various compounded drug products, including semaglutide. [B229] [B14] [B12] The following claim concerning compounded semaglutide products repeatedly appears on your website: • “generic semaglutide” Compounded drug products are not FDA-approved. [B111] [B112] [B11] [B127] [B89] [B9] [B10] [B2] [B3] [B19] [B1] [B8] [B17] [B0] [B16] [B4] [B13] [B21] [B7] [B6] Sincerely, /s/ George Tidmarsh, M.D., Ph.D. [B18] [B88] [B5] [B22] Content current as of: 09/16/2025 Regulated Product(s)

#### [67] simplerx-715874-09092025 | issued 09/09/2025 | SimpleRx | SUBJ: Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the Internet (Telehealth)
WARNING LETTER September 9, 2025 SimpleRx: This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your website content at the internet address https://rxmadesimple.com in August 2025 and has observed that your website offers various compounded drug products, including semaglutide and tirzepatide. [B47] [B14] [B12] [B74] “Semaglutide (Ozempic)” “Tirzepatide (Zepbound)” “Tirzepatide (generic Zepbound)” Compounded drug products are not FDA-approved. [B24] [B15] [B11] [B23] [B43] [B9] [B10] [B2] [B3] [B19] [B1] [B8] [B17] [B0] [B16] [B4] [B13] [B21] [B7] [B6] Sincerely, /S/ George Tidmarsh, M.D., Ph.D. [B18] Food and Drug Administration __________________________ 1 The semaglutide and tirzepatide products offered on your website 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. [B5] [B22] Content current as of: 09/16/2025 Regulated Product(s)

#### [68] slendid-716700-09092025 | issued 09/09/2025 | Slendid | SUBJ: Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the Internet (Telehealth)
WARNING LETTER September 9, 2025 Slendid: This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your website content at the internet address https://slendid.com in August 2025 and has observed that your website offers various compounded drug products, including semaglutide and tirzepatide. 1 As described below, your claim concerning compounded semaglutide and tirzepatide products is false or misleading under sections 502(a) and 502(bb) of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. §§ 352(a) and 352(bb)], resulting in products being introduced or delivered for introduction into interstate commerce in violation of section 301(a) of the FDCA [21 U.S.C. § 331(a)]. [B14] [B12] The following claim concerning compounded semaglutide and tirzepatide products appears on your website: “Clinically proven weight loss treatments” Compounded drug products are not FDA-approved. [B111] [B112] [B11] [B127] [B43] [B9] [B10] [B2] [B3] [B19] [B1] [B8] [B17] [B0] [B16] [B4] [B13] [B21] [B7] [B6] Sincerely, /S/ George Tidmarsh, M.D., Ph.D. [B18] Food and Drug Administration ____________________ 1 The semaglutide and tirzepatide products offered on your website 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. [B5] [B22] Content current as of: 09/16/2025 Regulated Product(s)

#### [69] sprout-health-partners-llc-dba-sprout-health-715879-09092025 | issued 09/09/2025 | Sprout Health Partners LLC dba Sprout Health | SUBJ: Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the Internet (Telehealth)
WARNING LETTER September 9, 2025 Sprout Health: This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your website content at the internet address https://joinsprouthealth.com in August 2025 and has observed that your website offers various compounded drug products, including semaglutide and tirzepatide. 1 As described below, your claim concerning compounded semaglutide and tirzepatide products is false or misleading under sections 502(a) and 502(bb) of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. §§ 352(a) and 352(bb)], resulting in products being introduced or delivered for introduction into interstate commerce in violation of section 301(a) of the FDCA [21 U.S.C. § 331(a)]. [B14] [B12] The following claim concerning compounded semaglutide and tirzepatide products appears on your website: “GLP-1 medications are FDA-approved and backed by extensive clinical research….” Compounded drug products are not FDA-approved. [B111] [B112] [B11] [B127] [B43] [B9] [B10] [B2] [B3] [B19] [B1] [B8] [B17] [B0] [B16] [B4] [B13] [B21] [B7] [B6] Sincerely, /S/ George Tidmarsh, M.D., Ph.D. [B18] Food and Drug Administration _____________________ 1 The semaglutide and tirzepatide products offered on your website 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. [B5] [B22] Content current as of: 09/16/2025 Regulated Product(s)

#### [70] trym-health-inc-dba-trym-health-716699-09092025 | issued 09/09/2025 | TRYM Health, Inc. dba TRYM Health | SUBJ: Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the Internet (Telehealth)
WARNING LETTER September 9, 2025 TRYM Health: This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your website content at the internet address https://trymhealth.com in August 2025 and has observed that your website offers various compounded drug products, including semaglutide and tirzepatide. [B47] [B14] [B12] [B74] “Clinically Proven to Work” “Contains the same active ingredient as Mounjaro and ZepBound [sic].” “Contains the same active ingredient as Ozempic and Wegovy.” Compounded drug products are not FDA-approved. [B24] [B15] [B11] [B23] [B43] [B9] [B10] [B2] [B3] [B19] [B1] [B8] [B17] [B0] [B16] [B4] [B13] [B21] [B7] [B6] Sincerely, /S/ George Tidmarsh, M.D., Ph.D. [B18] Food and Drug Administration ______________________ 1 The semaglutide and tirzepatide products offered on your website 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. [B5] [B22] Content current as of: 09/16/2025 Regulated Product(s)

#### [71] hcg-institute-716512-09092025 | issued 09/09/2025 | The HCG Institute | SUBJ: Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the Internet (Telehealth)
WARNING LETTER September 9, 2025 The HCG Institute: This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your website content at the internet address https://thehcginstitute.com in August 2025 and has observed that your website offers various compounded drug products, including semaglutide. [B207] [B14] [B12] The following claims concerning compounded semaglutide products appear on your website: • “Clinically proven to reduce appetite, lower food cravings, improve food intake regulation and glycemic control.” • “Compounded Generic Semaglutide is a revolutionary FDA-inspected medication for rapid weight loss that is given once weekly.” • “All of that said, we recognize that due to American drug marketing, many people only know of semaglutide either as ‘a GLP-1’ or ‘Ozempic’ rather than by the actual name or the preferred brand name. ‘Generic’ or compounded semaglutide, like what we sell here at the HCG Institute, are the same medication, as well.” Compounded drug products are not FDA-approved. [B24] [B15] [B11] [B23] [B89] [B9] [B10] [B2] [B3] [B19] [B1] [B8] [B17] [B0] [B16] [B4] [B13] [B21] [B7] [B6] Sincerely, /S/ George Tidmarsh, M.D., Ph.D. [B18] [B88] [B5] [B22] Content current as of: 09/16/2025 Regulated Product(s)

#### [72] try-nova-716695-09092025 | issued 09/09/2025 | Try Nova | SUBJ: Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the Internet (Telehealth)
WARNING LETTER September 9, 2025 Try Nova: This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your website content at the internet address https://trynovamd.com in August 2025 and has observed that your website offers various compounded drug products, including semaglutide. [B229] [B14] [B12] The following claim concerning compounded semaglutide products appears on your website: • “Same active ingredient as Wegovy & Ozempic.” Compounded drug products are not FDA-approved. [B111] [B112] [B11] [B127] [B89] [B9] [B10] [B2] [B3] [B19] [B1] [B8] [B17] [B0] [B16] [B4] [B13] [B21] [B7] [B6] Sincerely, /S/ George Tidmarsh, M.D., Ph.D. [B18] [B88] [B5] [B22] Content current as of: 09/16/2025 Regulated Product(s)

#### [73] tuyo-health-inc-dba-tuyo-health-716502-09092025 | issued 09/09/2025 | Tuyo Health, Inc. dba Tuyo Health | SUBJ: Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the Internet (Telehealth)
WARNING LETTER September 9, 2025 Tuyo Health: This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your website content at the internet address https://www.tuyohealth.com in August 2025 and has observed that your website offers various compounded drug products, including semaglutide and tirzepatide. [B47] [B14] [B12] The following claims concerning compounded semaglutide and tirzepatide products appear on your website: • “Same active as Wegovy and Ozempic” • “Same active ingredient as Zepbound and Mounjaro” • “With compounded semaglutide, you get the same trusted active ingredient as in brand-name medications….” Compounded drug products are not FDA-approved. [B24] [B15] [B11] [B23] [B43] [B9] [B10] [B2] [B3] [B19] [B1] [B8] [B17] [B0] [B16] [B4] [B13] [B21] [B7] [B6] Sincerely, /S/ George Tidmarsh, M.D., Ph.D. [B18] [B92] [B5] [B22] Content current as of: 09/16/2025 Regulated Product(s)

#### [74] vitals-rx-715868-09092025 | issued 09/09/2025 | Vitals RX | SUBJ: Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the Internet (Telehealth)
WARNING LETTER September 9, 2025 Vitals RX: This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your website content at the internet address https://vitalsrx.com in August 2025 and has observed that your website offers various compounded drug products, including semaglutide and tirzepatide. 1 As described below, your claim concerning compounded semaglutide and tirzepatide products is false or misleading under sections 502(a) and 502(bb) of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. §§ 352(a) and 352(bb)], resulting in products being introduced or delivered for introduction into interstate commerce in violation of section 301(a) of the FDCA [21 U.S.C. § 331(a)]. [B14] [B12] The following claim appears on your website, where the only semaglutide and tirzepatide products offered are compounded: • “Vitals RX - Semaglutide/Tirzepatide/Ozempic Weight Loss Clinic” Compounded drug products are not FDA-approved. [B111] [B112] [B11] [B127] [B43] [B9] [B10] [B2] [B3] [B19] [B1] [B8] [B17] [B0] [B16] [B4] [B13] [B21] [B7] [B6] Sincerely, /s/ George Tidmarsh, M.D., Ph.D. [B18] [B92] [B5] [B22] Content current as of: 09/16/2025 Regulated Product(s)

#### [75] directmedscom-inc-dba-directmeds-716822-09092025 | issued 09/09/2025 | directmeds.com, Inc. dba DirectMeds | SUBJ: Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the Internet (Telehealth)
WARNING LETTER September 9, 2025 DirectMeds: This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your website content at the internet address https://directmeds.com in August 2025 and has observed that your website offers various compounded drug products, including semaglutide and tirzepatide. [B47] [B14] [B12] The following claims concerning compounded semaglutide and tirzepatide products appear on your website: • “If you’ve looked into brand-name versions of semaglutide, you know the cost can be steep – especially without insurance. That’s where buying compounded semaglutide online can make a big difference. Compounded medications are created by licensed compounding pharmacies using the same active ingredients.” • “Compounded semaglutide contains the same active ingredient as branded semaglutide.” • “Don’t give up hope if brand-name Mounjaro is out of reach due to cost. You may be able to get compounded tirzepatide online, which is an effective and budget-friendly alternative. Compounded formulations use the same active ingredient as the brand-name drug, customized by licensed compounding pharmacies to meet your needs.” Compounded drug products are not FDA-approved. [B24] [B15] [B11] [B23] [B43] [B9] [B10] [B2] [B3] [B19] [B1] [B8] [B17] [B0] [B16] [B4] [B13] [B21] [B7] [B6] Sincerely, /s/ George Tidmarsh, M.D., Ph.D. [B18] [B92] [B5] [B22] Content current as of: 09/16/2025 Regulated Product(s)

#### [76] edrugstore-716505-09092025 | issued 09/09/2025 | eDrugstore | SUBJ: Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the Internet (Telehealth)
WARNING LETTER September 9, 2025 eDrugstore: This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your website content at the internet address https://www.edrugstore.com in August 2025 and has observed that your website offers various compounded drug products, including tirzepatide. 1 As described below, your claims concerning compounded tirzepatide products are false or misleading under sections 502(a) and 502(bb) of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. §§ 352(a) and 352(bb)], resulting in products being introduced or delivered for introduction into interstate commerce in violation of section 301(a) of the FDCA [21 U.S.C. § 331(a)]. [B14] [B12] The following claims concerning compounded tirzepatide products appear on your website: “FDA-Approved Active” “eDrugstore guarantees that all Tirzepatide medications are genuine, FDA-approved formulations for maximum efficacy and safety.” “Tirzepatide (Zepbound)….” Compounded drug products are not FDA-approved. [B24] [B15] [B11] [B23] 2 For the reasons discussed above, your compounded tirzepatide products are misbranded drugs under sections 502(a) and 502(bb) of the FDCA [21 U.S.C. §§ 352(a) and 352(bb)], introduced or delivered for introduction into interstate commerce in violation of section 301(a) of the FDCA [21 U.S.C. § 331(a)]. [B9] [B10] [B2] [B3] [B19] [B1] [B8] [B17] [B0] [B16] [B4] [B13] [B21] [B7] [B6] Sincerely, /S/ George Tidmarsh, M.D., Ph.D. [B18] Food and Drug Administration _________________________ 1 The tirzepatide products offered on your website 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. [B5] [B22] Content current as of: 09/16/2025 Regulated Product(s)

#### [77] ivisitdoc-inc-dba-ivisitdoc-716826-09092025 | issued 09/09/2025 | iVisitDoc, Inc. dba iVisitDoc | SUBJ: Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the Internet (Telehealth)
WARNING LETTER September 9, 2025 iVisitDoc: This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your website content at the internet address https://ivisitdoc.com in August 2025 and has observed that your website offers various compounded semaglutide drug products.1 As described below, your claims concerning compounded semaglutide products are false or misleading under sections 502(a) and 502(bb) of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. §§ 352(a) and 352(bb)], resulting in products being introduced or delivered for introduction into interstate commerce in violation of section 301(a) of the FDCA [21 U.S.C. § 331(a)]. [B14] [B12] The following claims concerning compounded semaglutide products appear on your website: • “Compounded semaglutide from iVisitDoc has the same active ingredients as Wegovy and Ozempic, but doesn’t come in a preloaded pen.” • “Clinically Validated Ingredients” Compounded drug products are not FDA-approved. [B24] [B15] [B11] The claims identified in this letter put you on notice of our concerns but do not represent an exhaustive list of misbranding violations.2 For the reasons discussed above, your compounded semaglutide products are misbranded drugs under sections 502(a) and 502(bb) of the FDCA [21 U.S.C. §§ 352(a) and 352(bb)], introduced or delivered for introduction into interstate commerce in violation of section 301(a) of the FDCA [21 U.S.C. § 331(a)]. [B9] [B10] [B2] [B3] [B19] [B1] [B8] [B17] [B0] [B16] [B4] [B13] [B21] [B7] [B6] Sincerely, /S/ George Tidmarsh, M.D., Ph.D. [B18] [B247] 09/16/2025 Regulated Product(s)

#### [78] inspireclinic-715799-09092025 | issued 09/09/2025 | inspire.clinic | SUBJ: Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the Internet (Telehealth)
WARNING LETTER September 9, 2025 inspire.clinic: This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your website content at the internet address https://www.inspire.clinic in August 2025 and has observed that your website offers various compounded drug products, including semaglutide and tirzepatide. [B47] [B14] [B12] The following claims concerning compounded semaglutide and tirzepatide products appear on your website: • “Semaglutide (similar to Ozempic) 2.5 mg vial” • “Tirzepatide (similar to Mounjaro) 10 mg vial” • “5 mg of semaglutide comparable to Ozempic. [sic]” Compounded drug products are not FDA-approved. [B24] [B15] [B11] [B23] [B43] [B9] [B10] [B2] [B3] [B19] [B1] [B8] [B17] [B0] [B16] [B4] [B13] [B21] [B7] [B6] Sincerely, /s/ George Tidmarsh, M.D., Ph.D. [B18] [B92] [B5] [B22] Content current as of: 09/16/2025 Regulated Product(s)

#### [79] ybycmeds-715878-09092025 | issued 09/09/2025 | ybycmeds | SUBJ: Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the Internet (Telehealth)
WARNING LETTER September 9, 2025 ybycmeds: This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your website content at the internet address https://ybycmeds.com in August 2025 and has observed that your website offers various compounded drug products, including semaglutide and tirzepatide. [B47] [B14] [B12] The following claims concerning compounded semaglutide and tirzepatide products appear on your website: • “Semaglutide for weight loss - Prefilled Syringes, similar to Ozempic or Wegovy” • “Tirzepatide for weight loss - Prefilled Syringes, similar to Mounjaro and Zepbound” • “Tirzepatide Peptide 60mg vial - similar to Mounjaro and Zepbound” • “Semaglutide Compound 10mg vial - similar to Ozempic or Wegovy” Compounded drug products are not FDA-approved. [B24] [B15] [B11] [B23] [B43] [B9] [B10] [B2] [B3] [B19] [B1] [B8] [B17] [B0] [B16] [B4] [B13] [B21] [B7] [B6] Sincerely, /S/ George Tidmarsh, M.D., Ph.D. [B18] [B92] [B5] [B22] Content current as of: 09/16/2025 Regulated Product(s)

#### [80] motionpharmacycom-715595-09102025 | issued 09/10/2025 | motionpharmacy.com | SUBJ: Unapproved New Drug/Misbranded
WARNING LETTER This is to advise you that the United States (U.S.) Food and Drug Administration (FDA) recently reviewed your website at the Internet address www.motionpharmacy.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.motionpharmacy.com introduces into interstate commerce unapproved and misbranded opioids. [B257] [B256] FDA has also observed that www.motionpharmacy.com introduces into interstate commerce unapproved and misbranded benzodiazepines. Benzodiazepines are drug products with an acknowledged potential for abuse, and it is important to address the public health impact of their nonmedical use. Benzodiazepine nonmedical use is widespread, and individuals frequently co‐use benzodiazepines with alcohol, prescription opioids, and illicit drugs. Associated harms of benzodiazepine nonmedical use are substantial but occur primarily when people use benzodiazepines in combination with other drugs. Further, in cases where benzodiazepines were co‐used with other substances, medical outcomes are typically more severe than in cases involving benzodiazepines alone. Polysubstance overdose deaths account for the vast majority of overdose deaths documenting involvement of benzodiazepines. Additionally, FDA has observed that www.motionpharmacy.com introduces into interstate commerce unapproved and misbranded Schedule II stimulants. Schedule II stimulants have an acknowledged high potential for abuse, and it is important to address the public health impact of their diversion and nonmedical use. Diversion is the primary source of prescription stimulants for nonmedical use, and nonmedical use is most frequent among young adults and college students. Polysubstance use is common among those who use prescription stimulants nonmedically, with individuals frequently co-using illicit drugs and/or prescription opioids. These concerns come against a backdrop of rising mortality from psychostimulant-involved overdoses, which involve illicit stimulants the vast majority of the time, but sometimes involve prescription stimulants. The easy availability of benzodiazepines and Schedule II stimulants via the Internet poses additional significant risks to U.S. consumers. Finally, FDA has observed that www.motionpharmacy.com introduces into interstate commerce unapproved and misbranded semaglutide drug products, including injectable versions. [B131] [B110] [B90] [B91] Accordingly, FDA requests that www.motionpharmacy.com cease offering any unapproved and misbranded drugs for sale to U.S. consumers. [B185] Unapproved New Drugs: Certain products offered for sale by www.motionpharmacy.com 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. [B109] [B100] [B98] [B97] Examples of unapproved opioids you offer for sale on www.motionpharmacy.com, including how these products are marketed on your website and evidence obtained from your website establishing that these products are drugs intended for human use (as defined in 21 CFR 201.128), are listed below: Unapproved opioid: Marketed as: Evidence includes the claim(s): hydrocodone bitartrate and acetaminophen “Hydrocodone” “Vicodine (Hydrocodone)” “Hydrocodone Bitartrate and Acetaminophen Tablets USP NDC 0591-0540-01” “Hydrocodone is a prescription medication at Motion Pharmacy classified as an opioid analgesic, primarily used to manage moderate to severe pain and to relieve coughing when combined with other medications.” hydromorphone hydrochloride (HCl) “Dilaudid” “Hydromorphone (Dilaudid)” “® pms-HYDROmorphone 4 mg” “® HYDROMORPH CONTIN® 4.5 mg” “® HYDROMORPH CONTIN® 8 mg” “® pms-HYDROmorphone 8 mg DIN 00885428” “Dilaudid is the brand name for hydromorphone, a powerful prescription opioid medication at Motion Pharmacy used to treat moderate to severe pain. It is often prescribed for patients who require relief from acute pain, such as post-surgical pain, or for chronic pain when other treatments are ineffective.” oxycodone HCl “Oxycontin” “Oxycontin (Oxycodone ER)” “OxyContin® 10 mg prolonged release tablets” “Oxycodone IR” “Oxycodone Immediate Release” “OxyContin is a prescription opioid pain medication at Motion Pharmacy. It is an extended-release formulation designed to manage severe, ongoing pain that requires around-the-clock treatment. It works by altering how the brain and nervous system perceive pain.” “Oxycodone IR (Immediate Release) at Motion Pharmacy is a potent prescription opioid medication used to relieve moderate to severe pain. It is a short-acting form of oxycodone, designed to provide quick relief from pain by releasing the active ingredient into the bloodstream rapidly.” oxycodone HCl and acetaminophen “Percocets” “DEPALGOS® 20 mg / 325 mg” “Percocet is commonly used to manage acute or chronic pain that cannot be controlled by non-opioid medications alone.” oxymorphone HCl “Oxymorphone” “Opana (Oxymorphone)” “Opana® ER (oxymorphone hydrochloride) Extended-Release Tablets” “Oxymorphone is a powerful prescription opioid analgesic used for the treatment of moderate to severe pain.” promethazine HCl “Promethazine” “Promethazine Syrop” “Promethazine Hydrochloride and Codeine Phosphate Oral Solution” “Promethazine with Codeine Oral Solution” “Wockhardt” “Akorn” “Tris” “Promethazine is an antihistamine commonly used for various medical purposes. It belongs to a class of drugs known as first-generation antihistamines, and it works by blocking the effects of histamine, a substance in the body involved in allergic reactions. It is often prescribed for allergy relief, but it has several other uses due to its sedative, anti-nausea, and anti-motion sickness properties.” While there are FDA-approved versions of hydrocodone bitartrate and acetaminophen, hydromorphone HCl (brand name DILAUDID), oxycodone HCl (brand name OXYCONTIN), oxycodone HCl and acetaminophen (brand name PERCOCET), oxymorphone HCl, and promethazine HCl and codeine phosphate oral solution 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 these drug products offered by www.motionpharmacy.com. Brand names VICODIN (hydrocodone bitartrate and acetaminophen), OPANA (oxymorphone HCl), and OPANA ER (oxymorphone HCl extended release) are discontinued. FDA-approved hydrocodone bitartrate and acetaminophen, hydromorphone HCl (brand name DILAUDID), oxycodone HCl, and oxycodone HCl and acetaminophen (brand name PERCOCET) are each indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. FDA-approved oxycodone HCl extended release (brand name OXYCONTIN) is indicated for the management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate. FDA-approved oxymorphone HCl is indicated for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. FDA-approved oxymorphone HCl extended release is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. FDA-approved promethazine HCl and codeine phosphate oral solution is indicated for the temporary relief of cough and upper respiratory symptoms associated with allergy or the common cold in patients 18 years of age and older. FDA-approved hydrocodone bitartrate and acetaminophen, hydromorphone HCl (brand name DILAUDID), oxycodone HCl (brand name OXYCONTIN), oxycodone HCl and acetaminophen (brand name PERCOCET), oxymorphone HCl, and promethazine HCl and codeine phosphate oral solution are only available pursuant to a prescription from a licensed practitioner. Furthermore, these drug products each 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. This boxed warning addresses risks including addiction, abuse, misuse, life-threatening respiratory depression (breathing problems), neonatal opioid withdrawal syndrome (withdrawal symptoms in newborn baby), and accidental exposure resulting in death. In addition, when these drug products are taken in conjunction with other central nervous system (CNS) depressants, including alcohol and benzodiazepines, use may result in coma or death. Examples of unapproved benzodiazepines you offer for sale on www.motionpharmacy.com, including how these products are marketed on your website and evidence obtained from your website establishing that these products are drugs intended for human use (as defined in 21 CFR 201.128), are listed below: Unapproved benzodiazepine: Marketed as: Evidence includes the claim(s): clonazepam “Clonazepam” “Rivotril (Clonazepam)” “Rivotril® 2 mg tabletta clonazepam 30 db” “Rivotril® tablet” “Rivotril is a brand name for the drug clonazepam, which is a benzodiazepine medication at Motion Pharmacy. It is primarily used to treat seizure disorders, anxiety disorders, and panic attacks. Rivotril works by calming the brain and nerves, which helps to reduce the frequency and severity of seizures and manage symptoms of anxiety.” diazepam “Diazepam” “Valium” “Valium® 10 mg comprimidos” “Diazepam is a medication belonging to the benzodiazepine class, commonly prescribed to treat a range of conditions by calming the central nervous system (CNS). It works by enhancing the effects of gamma-aminobutyric acid (GABA), a neurotransmitter that inhibits brain activity, resulting in a calming and relaxing effect.” estazolam “Estazolam” “Estazolam TZF” “Estazolam is a prescription medication belonging to the benzodiazepine class, commonly used to treat insomnia. It works by enhancing the effects of a neurotransmitter called gamma-aminobutyric acid (GABA) in the brain, which helps to produce a calming effect.” lorazepam “Lorazepam” “Ativan” “Ativan® (Lorazepam) 2 mg” “Lorazepam enhances the effects of gamma-aminobutyric acid (GABA), a neurotransmitter that calms the brain and nervous system. By increasing GABA activity, lorazepam reduces excessive nerve activity, leading to a calming effect” bromazepam “Bromazepam” “BROMAZÉPAM BIOGARAN® 6 mg” “Bromazepam 6 – 1 A Pharma® 6 mg Tabletten” “Bromazepam is a prescription medication belonging to the benzodiazepine class. It is primarily used for the short-term treatment of anxiety disorders, including excessive worry, agitation, and tension.” bromazolam “Bromazolam” “Bromazolam is a benzodiazepine medication that is chemically related to alprazolam (Xanax). It is primarily used for its anxiolytic (anxiety-reducing) and sedative properties. Bromazolam is not widely approved for medical use in many countries, but it has been available in some regions or online markets as a research chemical.” While there are FDA-approved versions of clonazepam (brand name KLONOPIN), diazepam (brand name VALIUM), estazolam, and lorazepam (brand name ATIVAN) 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 these drug products offered by www.motionpharmacy.com. Brand name PROSOM (estazolam) is discontinued. FDA-approved clonazepam (brand name KLONOPIN) is indicated for the treatment of certain seizure disorders and panic disorder with or without agoraphobia as defined in DSM-5. FDA-approved diazepam (brand name VALIUM) is indicated for anxiety disorders, acute alcohol withdrawal symptoms, skeletal muscle spasm relief, and as adjunctive therapy in convulsive disorders. FDA-approved estazolam is indicated for the short-term management of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. FDA-approved lorazepam (brand name ATIVAN) is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety or anxiety associated with depressive symptoms. There are no FDA-approved versions of bromazepam nor bromazolam on the market in the U.S., and there are no approved drug applications pursuant to section 505 of the FD&C Act in effect for bromazepam nor bromazolam offered by www.motionpharmacy.com. FDA-approved clonazepam (brand name KLONOPIN), diazepam (brand name VALIUM), estazolam, and lorazepam (brand name ATIVAN) are only available pursuant to a prescription from a licensed practitioner. Furthermore, these drug products each bear a boxed warning addressing risks including abuse, misuse, addiction, and physical dependence. In addition, the concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Examples of unapproved Schedule II stimulants you offer for sale on www.motionpharmacy.com, including how these products are marketed on your website and evidence obtained from your website establishing that these products are drugs intended for human use (as defined in 21 CFR 201.128), are listed below: Unapproved Schedule II stimulant: Marketed as: Evidence includes the claim(s): lisdexamfetamine dimesylate “Vyvanse” “Lisdexamphetamine” “Vyvanse® 50 mg Lisdexamfetamine dimesilate 50 mg” “Vyvanse (generic name: lisdexamfetamine dimesylate) is a prescription medication used to treat Attention Deficit Hyperactivity Disorder (ADHD) in adults and children aged six and older.” methylphenidate HCl “Concerta” “methylphenidate” “methylphenidate hydrochloride” “Concerta (Metilfenidato Clorhidrato) 36 mg” “Concerta XL 36 mg PL 00432/0373” “Ritalin” “Ritalin® LA Methylphenidate hydrochloride AUST R 82958” “Concerta is a prescription medication containing methylphenidate hydrochloride, a stimulant that affects chemicals in the brain and nerves that contribute to hyperactivity and impulse control.” “Ritalin is a prescription medication at Motion Pharmacy is primarily used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy, a sleep disorder. The active ingredient in Ritalin is methylphenidate, a stimulant that works by affecting certain chemicals in the brain that contribute to impulse control and hyperactivity.” While there are FDA-approved versions of lisdexamfetamine dimesylate and methylphenidate HCl 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 these drug products offered by www.motionpharmacy.com. FDA-approved lisdexamfetamine dimesylate (brand name VYVANSE) is indicated for the treatment of attention deficit hyperactivity disorder (ADHD) in adults and pediatric patients 6 years and older and moderate to severe binge eating disorder in adults. FDA-approved methylphenidate HCl (brand name RITALIN) is indicated for the treatment of ADHD in pediatric patients 6 years and older and adults and narcolepsy. Using the brand name of the drug product RITALIN indicates that this product is intended to treat ADHD and narcolepsy. FDA-approved methylphenidate HCl extended release is indicated for the treatment of ADHD, in pediatric patients 6 to 12 years of age (brand name RITALIN LA) and indicated for the treatment of ADHD in children 6 years of age and older, adolescents, and adults up to the age of 65 (brand name CONCERTA). FDA-approved lisdexamfetamine dimesylate (brand name VYVANSE) and methylphenidate HCl (brand names RITALIN, RITALIN LA, and CONCERTA) are only available pursuant to a prescription from a licensed practitioner. Furthermore, FDA-approved lisdexamfetamine dimesylate (brand name VYVANSE) and methylphenidate HCl (brand names RITALIN, RITALIN LA, and CONCERTA) each bear a boxed warning, addressing risks including abuse, misuse, and addiction. In addition, these drug products can be diverted for non-medical use into illicit channels or distribution. Misuse and abuse of CNS stimulants, including these drug products, can result in overdose and death, and this risk is increased with higher doses or unapproved methods of administration. An example of unapproved semaglutide you offer for sale on www.motionpharmacy.com, including how this product is marketed on your website and evidence obtained from your website establishing that this product is a drug intended for human use (as defined in 21 CFR 201.128), is listed below: Unapproved semaglutide: Marketed as: Evidence includes the claim(s): semaglutide “Ozempic” “OZEMPIC 1 mg” “OZEMPIC® 1 mg Injektionslösung im Fertigpen Semaglutid Subkutane Anwendung” “Increases insulin production: Helps regulate blood sugar after meals.” “Reduces glucagon secretion: Lowers blood sugar levels by preventing excessive sugar release from the liver.” 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 semaglutide offered by www.motionpharmacy.com. [B165] FDA-approved semaglutide tablets (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 injection (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 (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 products also bear a boxed warning, which again, is the strongest warning FDA requires, indicating that the drug carries a significant risk of serious or even life-threatening adverse effects. [B116] Misbranded Drugs: [B101] [B108] [B214] [B213] [B124] [B255] [B254] By offering these drugs for sale to U.S. consumers, www.motionpharmacy.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)]. FDA has also observed that the www.motionpharmacy.com offers prescription drugs for sale without a prescription. In addition to the aforementioned drugs, examples of misbranded opioids you offer for sale on www.motionpharmacy.com, including how these products are marketed on your website and evidence obtained from your website establishing that these products are drugs intended for human use (as defined in 21 CFR 201.128), are listed below: Misbranded opioid: Marketed as: Evidence includes the claim(s): buprenorphine HCl “Buprenorphine” “Buprenorphine Sublingual Tablets NDC 0054-0177-13” “Buprenorphine is a prescription medication used primarily for the treatment of opioid use disorder (OUD) and for managing moderate to severe pain. It is classified as a partial opioid agonist, meaning it activates opioid receptors in the brain to a lesser extent than full agonists like heroin or oxycodone.” buprenorphine HCl and naloxone HCl “Suboxone” “Suboxone (Buprenorphine and Naloxone)” “Suboxone® (buprenorphine and naloxone) sublingual film 8 mg/2 mg NDC 12496-1208-3” “Suboxone is a prescription medication used in the treatment of opioid dependence and addiction. It is a combination of two active ingredients: buprenorphine, a partial opioid agonist, and naloxone, an opioid antagonist. Together, these ingredients help reduce withdrawal symptoms and cravings while discouraging misuse.” morphine sulfate “Morphine “Morphine Sulphate “Morphine Sulphate Oral Solution NDC 0406-8003-30” “Morphine Sulphate Extended-Release Capsule NDC 0228-3090-11” “Morphine sulfate is a powerful opioid medication commonly prescribed to manage moderate to severe pain. It belongs to a class of drugs called opioid analgesics, which work by binding to opioid receptors in the brain and spinal cord.” FDA-approved buprenorphine HCl is indicated for the treatment of opioid dependence and is preferred for induction. FDA-approved buprenorphine HCl and naloxone HCl (brand name SUBOXONE) is indicated for treatment of opioid dependence. Both drug products are indicated to be used as part of a complete treatment plan to include counseling and psychosocial support. FDA-approved morphine sulfate is indicated for the management of acute or chronic pain severe enough to require an opioid analgesic. FDA-approved morphine sulfate extended release is indicated for the management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic. Both drug products are indicated for which alternative treatment options are inadequate. FDA-approved buprenorphine HCl, buprenorphine HCl and naloxone HCl (brand name SUBOXONE), and morphine sulfate are only available pursuant to a prescription from a licensed practitioner. Furthermore, FDA-approved buprenorphine HCl, buprenorphine HCl and naloxone HCl (brand name SUBOXONE), and morphine sulfate each bear a boxed warning addressing risks including addiction, abuse, misuse, life-threatening respiratory depression, neonatal opioid withdrawal syndrome, and accidental exposure resulting in death. In addition, when these drug products are taken in conjunction with other CNS depressants, including alcohol and benzodiazepines, use may result in coma or death. An example of a misbranded benzodiazepine you offer for sale on www.motionpharmacy.com, including how this product is marketed on your website and evidence obtained from your website establishing that this product is a drug intended for human use (as defined in 21 CFR 201.128), is listed below: Misbranded benzodiazepine: Marketed as: Evidence includes the claim(s): alprazolam “Alprazolam” “Xanax” “alprazolam tablets, USP 1 mg NDC 59762-3721-1” “alprazolam XR, extended-release tablets, 3 mg NDC 59762-0068-1” “Alprazolam Tablets, USP 2 mg NDC 51991-707-05” “Xanax is a brand name for alprazolam, a medication in the benzodiazepine class. It is used primarily to treat anxiety disorders, including generalized anxiety disorder (GAD) and panic disorder. Alprazolam works by enhancing the effects of gamma-aminobutyric acid (GABA), a neurotransmitter that reduces brain activity and has a calming effect on the nervous system.” FDA-approved alprazolam (brand name XANAX) is indicated for the acute treatment of generalized anxiety disorder and panic disorder with or without agoraphobia. FDA-approved alprazolam (brand name XANAX) is only available pursuant to a prescription from a licensed practitioner. Furthermore, this drug product bears a boxed warning addressing risks including abuse, misuse, addiction, and physical dependence. In addition, the concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Examples of misbranded Schedule II stimulants you offer for sale on www.motionpharmacy.com, including how these products are marketed on your website and evidence obtained from your website establishing that these products are drugs intended for human use (as defined in 21 CFR 201.128), are listed below: Misbranded Schedule II stimulant: Marketed as: Evidence includes the claim(s): amphetamine “Adderall” “Adderall (Dextroamphetamine/amphetamine)” “ADDERALL XR® NDC 54092-383-01” “Adderall is a prescription medication at Motion Pharmacy that contains a combination of two stimulant drugs: amphetamine and dextroamphetamine. It is primarily used to treat Attention Deficit Hyperactivity Disorder (ADHD) and narcolepsy (a sleep disorder).” dextroamphetamine sulfate “Dextroamphetamine” “Dextroamphetamine Sulphate” “Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets NDC 0555-0973-02” “Dextroamphetamine Sulphate Tablets, USP NDC 52536-500-03” “Dextroamphetamine sulfate is a stimulant medication commonly used to treat Attention Deficit Hyperactivity Disorder (ADHD) and narcolepsy.” “Dextroamphetamine sulfate works by increasing the levels of certain chemicals (neurotransmitters) in the brain, particularly dopamine and norepinephrine, which help improve focus, attention, and impulse control in people with ADHD.” FDA-approved amphetamine (brand name ADDERALL) is indicated for the treatment of ADHD and narcolepsy. Using the brand name of the drug product ADDERALL indicates that this product is intended to treat ADHD and narcolepsy. FDA-approved amphetamine extended release (brand name ADDERALL XR) is indicated for the treatment of ADHD in adults and pediatric patients 6 years and older. FDA-approved dextroamphetamine sulfate is indicated for narcolepsy and ADHD in patients ages 3 to 16 years. FDA-approved amphetamine (brand name ADDERALL), amphetamine extended release (brand name ADDERALL XR), and dextroamphetamine sulfate are only available pursuant to a prescription from a licensed practitioner. Furthermore, FDA-approved amphetamine (brand name ADDERALL), amphetamine extended release (brand name ADDERALL XR), and dextroamphetamine sulfate each bear a boxed warning, addressing risks including abuse, misuse, and addiction. In addition, these drug products can be diverted for non-medical use into illicit channels or distribution. Misuse and abuse of CNS stimulants, including these drug products, can result in overdose and death, and this risk is increased with higher doses or unapproved methods of administration. [B248] By offering the aforementioned drugs without requiring a prescription, www.motionpharmacy.com jeopardizes patient safety and misbrands the drugs under section 503(b)(1) of the FD&C Act. [B134] FDA is sending this warning letter to www.motionpharmacy.com because of the inherent risks to consumers who purchase misbranded and unapproved new drugs. [B96] [B94] [B93] 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 and unapproved drug products in violation of the FD&C Act. [B103] [B104] Failure to adequately address this matter may result in legal action, including, without limitation, seizure, and injunction, without further notice. [B102] [B83] [B99] [B81] [B95] [B117] [B223] Acting Director Office of Drug Security, Integrity, and Response Office of Compliance Center for Drug Evaluation and Research Content current as of: 09/23/2025 Regulated Product(s)

#### [81] chengdu-brilliant-biopharmaceutical-co-ltd-711330-09112025 | issued 09/11/2025 | Chengdu Brilliant Biopharmaceutical Co., Ltd. | SUBJ: CGMP/Finished Pharmaceuticals/Adulterated
WARNING LETTER Chengdu Brilliant Biopharmaceutical Co., Ltd. MARCS-CMS 711330 — September 11, 2025 More Warning Letters Delivery Method: Via Electronic Mail Return Confirmation Requested Reference #: 320-25-109 Product: Drugs Recipient: Recipient Name Mr. Zeng Dong Recipient Title General Manager Chengdu Brilliant Biopharmaceutical Co., Ltd. #33, Tengfei 12th Rd, Southwest Airport Economic Dev Zn Shuangliu Xian Chengdu Shi Sichuan Sheng , 610207 China Issuing Office: Center for Drug Evaluation and Research (CDER) United States Warning Letter 320-25-109 September 11, 2025 Dear Mr. Zeng Dong: Your facility is registered with the United States Food and Drug Administration (FDA) as a manufacturer of active pharmaceutical ingredients (APIs). FDA has reviewed the records you submitted in response to our March 12, 2025, request 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, Chengdu Brilliant Biopharmaceutical Co., Ltd., FEI 3015530591, at #33, Tengfei 12th Road, Southwest Airport Economic Dev Zn, Shuangliu District Chengdu, Sichuan. 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 of drugs as described in your response to our 704(a)(4) request 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). Following review of records and other information provided pursuant to section 704(a)(4) of the FD&C Act, significant deviations were observed including, but not limited to, the following: 1. Failure to demonstrate that your manufacturing process can reproducibly manufacture an API meeting its predetermined quality attributes. Based on the records and information you provided, your firm has not conducted process validation for the Glucagon-Like Peptide-1 Receptor Agonist (GLP-1) API Semaglutide manufactured at your site. Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and ensure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies determine whether an initial state of control has been established. Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure that you maintain a stable manufacturing operation throughout the product lifecycle. Without adequate process validation, your firm lacks basic assurance that you can reproducibly deliver products that meet specifications. See FDA’s guidance document Process Validation: General Principles and Practices for general principles and approaches that FDA considers appropriate elements of process validation, at https://www.fda.gov/media/71021/download. In response to this letter, provide the following: A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures. Describe your program for process performance qualification (PPQ), and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control. A timeline for performing PPQ for each of your marketed drug products. Process performance protocol(s) and written procedures for qualification of equipment and facilities. A detailed program for designing, validating, maintaining, controlling and monitoring each of your manufacturing processes that includes vigilant monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control. Also, include your program for qualification of your equipment and facility. 2. Failure to test the identity of each batch of incoming production material. Based on the records and information you provided, you failed to conduct an identity test on the raw materials used for manufacturing of your API during (b)(4) , e.g., (b)(4) . Without adequate testing, there is no scientific evidence to assure that your raw materials conform to appropriate specifications before release. In response to this letter, please provide the following: A comprehensive, independent review of your material system to determine whether all suppliers of components, containers, and closures, are each qualified and the materials are assigned appropriate expiration or retest dates. The review should also determine whether incoming material controls are adequate to prevent use of unsuitable components, containers, and closures. The chemical and microbiological quality control specifications you use to test and release each incoming lot of component for use in manufacturing. A description of how you will test each component lot for conformity with all appropriate specifications for identity, strength, quality, and purity. If you intend to accept any results from your supplier’s Certificates of Analysis (COA) instead of testing each component lot for strength, quality, and purity, specify how you will robustly establish the reliability of your supplier’s results through initial validation as well as periodic re-validation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot. A summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer. Include your SOP that describes this COA validation program. A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture. Conclusion The 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. FDA placed all drugs and drug products offered for import into the United States from your firm on Import Alert 66-40 on July 9, 2025. 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 inspect to verify that you have completed corrective actions to any deviations. Failure to address any deviations may also result in the FDA continuing to refuse admission of articles manufactured at Chengdu Brilliant Biopharmaceutical Co., Ltd., FEI 3015530591, at #33, Tengfei 12th Road, Southwest Airport Economic Dev Zn, Shuangliu District Chengdu 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. [B279] [B282] In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. [B281] [B280] Identify your response with FEI 3015530591 and ATTN: Chhaya Shetty. Sincerely, /S/ Francis Godwin Director Office of Manufacturing Quality Office of Compliance Center for Drug Evaluation and Research Content current as of: 09/23/2025 Regulated Product(s)

#### [82] ralph-defronzo-md-716773-09172025 | issued 09/17/2025 | Ralph A. DeFronzo, M.D. | SUBJ: Clinical Investigator/Sponsor
WARNING LETTER FDA Ref No.: 25-HFD-45-09-02 Dear Dr. DeFronzo: This Warning Letter informs you of objectionable conditions observed during the U.S. Food and Drug Administration (FDA) inspection conducted at your clinical site between December 3 and December 6, 2024. Investigator Ruth E. Medcalf, representing FDA, reviewed your conduct of the following clinical investigations: Protocol (b)(4) , “ (b)(4) ,” of the investigational drugs (b)(4) , performed for (b)(4) . 1 Protocol (b)(4) , “ (b)(4) ,” of the investigational drug (b)(4) , performed for (b)(4) . This inspection was conducted as a part of FDA’s Bioresearch Monitoring Program, which includes inspections designed to evaluate the conduct of research and to help ensure that the rights, safety, and welfare of human subjects have been protected. At the conclusion of the inspection, Investigator Medcalf presented and discussed with you the Form FDA 483, Inspectional Observations. We acknowledge receipt of your December 30, 2024, written response to the Form FDA 483. From our review of the FDA Establishment Inspection Report, the documents submitted with that report, and your written response dated December 30, 2024, it appears that you did not adhere to the applicable statutory requirements in the Federal Food, Drug, and Cosmetic Act (FD&C Act) and applicable regulations contained in Title 21 of the Code of Federal Regulations, part 312 (21 CFR 312) governing the conduct of clinical investigations and the protection of human subjects. We wish to emphasize the following: 1. You failed to ensure that the investigation was conducted according to the investigational plan [21 CFR 312.60]. As a clinical investigator, you are required to ensure that your clinical studies are conducted in accordance with the investigational plan. The investigational plan for Protocol (b)(4) required you to ensure that subjects met all eligibility criteria before enrollment in the study. For example, all versions of the protocol that was in effect at the time all seven subjects enrolled, required the following inclusion criteria to be eligible for enrollment in the study: blood pressure ≤ 145 / 65 mmHg estimated glomerular filtration rate (eGFR) > 45 ml/min/1.73m² Furthermore, the eligibility criteria for Protocol (b)(4) required subjects who were treated with glucagon-like peptide-1 (GLP-1) receptor agonists or thiazolidinediones, and with sodium-glucose transport protein 2 (SGLT2) inhibitors, to be excluded from participation in the study. You failed to adhere to these requirements. Specifically: a. Subject (b)(6) ’s screening visit blood pressure was 103 / 72 mmHg, which was outside the protocol-specified range for eligibility. However, this subject was enrolled on July 12, 2023, and received study drug. b. Subject (b)(6) ’s screening visit blood pressure was 163 / 92 mmHg, and the subject’s eGFR was 41 ml/min/1.73m², both of which fell outside the protocol-specified ranges for eligibility. Additionally, this subject’s medication list included FARXIGA® (dapagliflozin), an SGLT2 inhibitor, which was an exclusionary medication for study enrollment. However, this subject was enrolled on July 25, 2023, and received study drug. c. Subject (b)(6) ’s medication list included JARDIANCE® (empagliflozin), an SGLT2 inhibitor, which was an exclusionary medication for study enrollment. However, this subject was enrolled on July 26, 2023, and received study drug. d. Subject (b)(6) ’s screening visit blood pressure was 120 / 78 mmHg, which was outside the protocol-specified range for eligibility. However, this subject was enrolled on August 7, 2023, and received study drug. e. Subject (b)(6) ’s screening visit blood pressure was 132 / 67 mmHg, which was outside the protocol-specified range for eligibility. This subject’s medication list included JARDIANCE® (empagliflozin), an SGLT2 inhibitor, and SOLIQUA®, which is a combination of insulin glargine and lixisenatide, a GLP-1 receptor agonist, both of which were exclusionary medications for study enrollment. However, this subject was enrolled on August 9, 2023, and received study drug. f. Subject (b)(6) ’s screening visit blood pressure was 112 / 74 mmHg, which was outside the protocol-specified range for eligibility. Also, this subject’s medication list included JARDIANCE® (empagliflozin), an SGLT2 inhibitor, which was an exclusionary medication for study enrollment. However, this subject was enrolled on June 18, 2024, and received study drug. In your December 30, 2024, written response, you stated that the blood pressure requirement defined in the eligibility criteria was a typographical error, and that you modified the protocol accordingly in the protocol version approved by the IRB in September 2024. In this version of the protocol, you also modified the eligibility criteria to allow for eGFR variability, and to allow for inclusion of subjects taking SLGT2 inhibitors and GLP-1 receptor agonists. You noted that the guidelines for (b)(4) therapy have changed significantly since the protocol was first written, noting the benefit of SLGT2 inhibitors and GLP-1 receptor agonists. Your written response further stated that all staff and physicians involved in ongoing clinical studies have been retrained, and all new staff will be thoroughly trained. You also indicated that, for all ongoing studies, a second person involved in the study has been identified, and this second person will check that the eligibility criteria in the protocol and source documents are internally consistent and do not contain any typos. You stated that this person will also check that participants fulfill inclusion/exclusion criteria, and that you will review and sign the inclusion/exclusion page. While we acknowledge your response that you made the necessary changes to the protocol and obtained IRB approval, your response is inadequate because this approval of the protocol with the above-noted modified inclusion criteria occurred more than a year after all seven subjects were enrolled. Further, your corrective actions are inadequate because your written response does not provide sufficient details about how you, as a clinical investigator, will ensure adequate oversight of the study procedures and will prevent similar violations in the future. We emphasize that as the clinical investigator, it is your responsibility to ensure that studies are conducted in accordance with the investigational plan, both to protect the rights, safety, and welfare of subjects and to ensure the integrity of study data. Your failure to ensure that subjects met eligibility criteria before their enrollment in the study raises significant concerns about the safety of subjects enrolled in this study and the reliability of data at your site. 2. You failed to promptly report all changes in research activity to the Institutional Review Board (IRB) [21 CFR 312.66]. As a clinical investigator, you are required to promptly report all changes in research activity to the IRB. You failed to adhere to this requirement. Specifically, for Protocol (b)(4) , you did not promptly report to the IRB that the study design of the clinical investigation was modified from a double-blind, placebo-controlled, randomized clinical trial to a two-part clinical trial that included an initial pilot feasibility study of 10 to 12 participants, followed by a double-blind, placebo-controlled, randomized clinical trial. As a result, all seven enrolled subjects received the investigational drug, because the change in study design eliminated the placebo control group; further, this occurred before you received IRB approval for the modification on September 23, 2024. We note that the approval of the protocol with the above-noted modified study design occurred more than one year after all seven subjects were enrolled and treated with the investigational drug. Additionally, we are particularly concerned that all seven enrolled subjects were consented using an informed consent document that detailed the study procedures, risks, benefits, and rights of study participants for the original double-blind, placebo-controlled, randomized clinical trial, not for the clinical trial with the modified study design that included the initial pilot feasibility study. In your December 30, 2024, written response, you acknowledged that the protocol needed to reflect exactly how the subjects are enrolled into the study. You stated that you had addressed this issue with the IRB, including that you have since updated the informed consent form for this study. You also explained that all study participants were verbally informed at the time of consent that they would receive study drug ( (b)(4) ) and not a placebo. You noted that all staff and physicians involved in ongoing clinical studies have been retrained, and that all new staff will be thoroughly trained, which will include their attending IRB training courses. While we acknowledge the corrective actions that your site has taken and plans to take, your response is inadequate because you have not provided sufficient details about your corrective action plan. For example, you did not provide sufficient details about the policies, procedures, and training plan being implemented at your site to prevent similar violations in the future. We emphasize that, as the clinical investigator, you are responsible for promptly reporting to the IRB all changes in research activity. Your failure to promptly report all changes in research activity to the IRB prevented the IRB from making an informed determination regarding the continued protection of the rights, safety, and welfare of human subjects enrolled in your clinical investigation. This failure potentially compromised the ethical conduct of the study and the validity of the informed consent process for all seven enrolled subjects. This letter is not intended to be an all-inclusive list of deficiencies with your clinical study of an investigational drug. It is your responsibility to ensure adherence to each requirement of the law and relevant FDA regulations. You should address any deficiencies and establish procedures to ensure that any ongoing or future studies comply with FDA regulations. This letter notifies you of our findings and provides you with an opportunity to address the deficiencies noted above. Within 15 business days of your receipt of this letter, you should notify this office in writing of the actions you have taken to prevent similar violations in the future. Failure to adequately address this matter may lead to regulatory action. If you believe that you have complied with the FD&C Act and relevant regulations, please include your reasoning and any supporting information for our consideration. Should you have any questions or concerns about this letter or the inspection, please email FDA at CDER-OSI-Communications@fda.hhs.gov. Your written response and any pertinent documentation should be addressed to: Brittany L. Garr-Colón, MPH Branch Chief Compliance Enforcement Branch Division of Enforcement and Postmarketing Safety Office of Scientific Investigations Office of Compliance Center for Drug Evaluation and Research U.S. Food and Drug Administration Building 51, Room 5352 10903 New Hampshire Avenue Silver Spring, MD 20993 Sincerely yours, {See appended electronic signature page} David C. Burrow, Pharm.D., J.D. Director Office of Scientific Investigations Office of Compliance Center for Drug Evaluation and Research U.S. Food and Drug Administration -------------------------------------------------------------------------------------------- This is a representation of an electronic record that was signed electronically. Following this are manifestations of any and all electronic signatures for this electronic record. -------------------------------------------------------------------------------------------- /s/ ------------------------------------------------------------ DAVID C BURROW 09/17/2025 06:49:26 AM _____________________________ 1 Protocol (b)(4) was performed under an investigational new drug application, sponsored by (b)(4) , M.D., for the use of investigational drug (b)(4) in this clinical investigation. Content current as of: 09/23/2025 Regulated Product(s)