[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"fda-warning-letter-hybrid-pharma-llc-629021-06072022":3,"fda-latest-sync-dates":29},{"id":4,"letter_id":5,"action_type":6,"firm_name":7,"fei_number":8,"issuing_office":9,"subject":10,"posted_date":11,"action_taken_date":12,"response_letter_date":8,"closeout_date":8,"case_status":13,"letter_url":14,"reference_number":8,"marcs_cms_no":15,"product_type":16,"delivery_method":8,"recipient_name":17,"recipient_title":8,"body_html":18,"body_text":19,"body_fetched_at":20,"medical_device_id":8,"raw":21,"created_at":27,"updated_at":28},2625,"hybrid-pharma-llc-629021-06072022","Warning Letter","Hybrid Pharma, LLC",null,"Office of Pharmaceutical Quality Operations, Division II","Compounding Pharmacy\u002FAdulterated Drug Products","2022-06-14","2022-06-07","Issued","https:\u002F\u002Fwww.fda.gov\u002Finspections-compliance-enforcement-and-criminal-investigations\u002Fwarning-letters\u002Fhybrid-pharma-llc-629021-06072022","629021","Drugs","Ponswamy Rajalingam, Ph.D.","\n\n                            \n                            \n                            \n                            \n                                              \n  \n \n\n                 \n\n \n\n\u003Cdiv class=\"inset-column\">\n  \u003Cdl class=\"lcds-description-list--grid\">\n\n      \n      \n              \u003Cdt class=\"cell-1_3\">Product:\u003C\u002Fdt> \n        \u003Cdd class=\"cell-2_3\">Drugs                          \n            \n            \n            \n            \n            \n            \n            \n             \n            \n            \n            \n              \n            \n            \n            \u003C\u002Fdd>\n      \n          \u003C\u002Fdl>\n  \u003C\u002Fdiv>            \n\n\n\u003Chr>\n\n\u003Cdiv class=\"row inset-column\">\n  \u003Cdiv class=\"col-xs-12 col-md-6\">\n    \u003Cdl class=\"\">\n\n        \u003Cdt>Recipient:\u003C\u002Fdt>\n\n                      \u003Cdd>\n  \u003Cdiv class=\"field field--name-field-recipient-name field--type-string field--label-above\">\n    \u003Cdiv class=\"field--label\">Recipient Name\u003C\u002Fdiv>\n              \u003Cdiv class=\"field--item\">Ponswamy Rajalingam, Ph.D.\u003C\u002Fdiv>\n          \u003C\u002Fdiv>\n\u003C\u002Fdd>\n                                \u003Cdd>\n  \u003Cdiv class=\"field field--name-field-recipient-title field--type-string field--label-above\">\n    \u003Cdiv class=\"field--label\">Recipient Title\u003C\u002Fdiv>\n              \u003Cdiv class=\"field--item\">Owner and President\u003C\u002Fdiv>\n          \u003C\u002Fdiv>\n\u003C\u002Fdd>\n          \n            \u003Cdd>Hybrid Pharma, LLC\u003C\u002Fdd>\n\n          \n                      \u003Cdd>\u003Cp class=\"address\" translate=\"no\">\u003Cspan class=\"address-line1\">1015 West Newport Center Drive, Suite 106-A\u003C\u002Fspan>\u003Cbr>\n\u003Cspan class=\"locality\">Deerfield Beach\u003C\u002Fspan>, \u003Cspan class=\"administrative-area\">FL\u003C\u002Fspan> \u003Cspan class=\"postal-code\">33442-7707\u003C\u002Fspan>\u003Cbr>\n\u003Cspan class=\"country\">United States\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fdd>\n          \n          \n          \n    \u003C\u002Fdl>\n  \u003C\u002Fdiv>            \n\n       \u003Cdiv class=\"col-xs-12 col-md-6\">\n    \u003Cdl class=\"\">\n          \n          \u003Cdt>Issuing Office:\u003C\u002Fdt>\n        \n         \n          \u003Cdd>Office of Pharmaceutical Quality Operations, Division II\u003C\u002Fdd>\n        \n         \n          \u003Cdd>\u003Cp class=\"address\" translate=\"no\">\u003Cspan class=\"country\">United States\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fdd>\n        \n        \n        \n        \n        \n    \u003C\u002Fdl>\n    \u003Cdl class=\"\"> \n      \n    \u003C\u002Fdl>\n  \u003C\u002Fdiv>  \n      \n\u003C\u002Fdiv>\n\n \n\n \n\n\u003Chr>\n\n\u003Cp>DATE: June 7, 2022\u003C\u002Fp>\n\n\u003Cp>Case #: 629021\u003C\u002Fp>\n\n\u003Cp class=\"text-align-center\">\u003Cstrong>WARNING LETTER\u003C\u002Fstrong>\u003C\u002Fp>\n\n\u003Cp>Dr. Rajalingam:\u003C\u002Fp>\n\n\u003Cp>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]\u003Csup>\u003Cem>\u003Cstrong>1\u003C\u002Fstrong>\u003C\u002Fem>\u003C\u002Fsup> on January 14, 2015, and most recently on November 24, 2021. From July 27, 2021 to September 3, 2021, an FDA investigator inspected your facility, Hybrid Pharma, LLC, located at 1015 West Newport Center Drive, Suite 106-A, Deerfield Beach, Florida 33442. 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 sterile drug products, which put patients at risk.\u003C\u002Fp>\n\n\u003Cp>FDA issued a Form FDA 483 to your facility on September 3, 2021. FDA acknowledges receipt of your facility’s response, dated September 24, 2021. Based on this inspection, it appears you produced drugs that violate the FDCA.\u003C\u002Fp>\n\n\u003Cp>\u003Cstrong>A. Compounded Drug Products under the FDCA\u003C\u002Fstrong>\u003C\u002Fp>\n\n\u003Cp>Under 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.\u003Csup>\u003Cem>\u003Cstrong>2\u003C\u002Fstrong>\u003C\u002Fem>\u003C\u002Fsup>\u003C\u002Fp>\n\n\u003Cp>An 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.\u003C\u002Fp>\n\n\u003Cp>In addition, for a compounded drug product to qualify for the exemptions under section 503B, it must be compounded in an outsourcing facility that is in compliance with the registration and reporting requirements in section 503B(b) including the requirement to submit a report to FDA upon initially registering as an outsourcing facility, once in June of each year, and once in December of each year identifying the drug products compounded during the previous 6-month period (section 503B(b)(2) of the FDCA [21 U.S.C. §353b(b)(2)]).\u003C\u002Fp>\n\n\u003Cp>\u003Cstrong>B. Failure to Meet the Conditions of Section 503B\u003C\u002Fstrong>\u003C\u002Fp>\n\n\u003Cp>During 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 collected evidence indicating that your facility failed to submit a complete report to FDA in December 2020 and June 2021, identifying all the drug products that you compounded during the previous 6-month period, including Phosphatidyl choline 5% and deoxycholate 4.2% injectable and \u003Cstrong>(b)(4)\u003C\u002Fstrong> Injection (section 503B(b)(2) of the FDCA [21 U.S.C. §353b(b)(2)]).\u003C\u002Fp>\n\n\u003Cp>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.\u003C\u002Fp>\n\n\u003Cp>Specific violations are described below.\u003C\u002Fp>\n\n\u003Cp>\u003Cstrong>C. Violations of the FDCA\u003C\u002Fstrong>\u003C\u002Fp>\n\n\u003Cp>\u003Cstrong>Adulterated Drug Products\u003C\u002Fstrong>\u003Cbr>\n\u003Cbr>\nThe FDA investigator 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.\u003Cbr>\nThe violations include, for example:\u003C\u002Fp>\n\n\u003Cp>1. 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).\u003C\u002Fp>\n\n\u003Cp>2. Your firm failed to establish the accuracy, sensitivity, specificity, and reproducibility of its test methods (21 CFR 211.165(e)).\u003C\u002Fp>\n\n\u003Cp>3. Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).\u003C\u002Fp>\n\n\u003Cp>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, \u003Cem>Current Good Manufacturing Practice — Guidance for Human Drug Compounding Outsourcing Facilities under Section 503B of the FD&C Act\u003C\u002Fem>. 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.\u003C\u002Fp>\n\n\u003Cp>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.\u003C\u002Fp>\n\n\u003Cp>\u003Cstrong>Unapproved New Drug Products\u003C\u002Fstrong>\u003C\u002Fp>\n\n\u003Cp>You do not have any FDA-approved applications on file for drug products that you compound.\u003Csup>\u003Cem>\u003Cstrong>3\u003C\u002Fstrong>\u003C\u002Fem>\u003C\u002Fsup> Under 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.\u003C\u002Fp>\n\n\u003Cp>\u003Cstrong>Misbranded Drug Products\u003C\u002Fstrong>\u003C\u002Fp>\n\n\u003Cp>You 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.\u003Csup>\u003Cem>\u003Cstrong>4\u003C\u002Fstrong>\u003C\u002Fem>\u003C\u002Fsup> The 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.\u003C\u002Fp>\n\n\u003Cp>\u003Cstrong>Failure to Report Drugs\u003C\u002Fstrong>\u003C\u002Fp>\n\n\u003Cp>As noted above, your facility failed to submit a complete report to FDA in December\u003Cbr>\n2020 and again in June 2021, identifying the drug products that you compounded during\u003Cbr>\nthe previous 6-month period (section 503B(b)(2) of the FDCA). The failure to report\u003Cbr>\ndrugs by an entity that is registered with FDA in accordance with section 503B(b) is a\u003Cbr>\nprohibited act under section 301(ccc)(3) of the FDCA [21 U.S.C. § 331(ccc)(3)].\u003C\u002Fp>\n\n\u003Cp>\u003Cstrong>D. Corrective Actions\u003C\u002Fstrong>\u003C\u002Fp>\n\n\u003Cp>We have reviewed your facility’s response to the Form FDA 483.\u003C\u002Fp>\n\n\u003Cp>We are unable to fully evaluate some of your corrective actions due to lack of adequate supporting documentation:\u003C\u002Fp>\n\n\u003Cp>1. In response to Observation 1 of the Form FDA 483, you state that your investigation was extended to other batches and bulk drug samples were submitted to the manufacturer. However, you did not provide:\u003Cbr>\na. Copies of completed investigation reports.\u003Cbr>\nb. Documentation showing visual inspections were performed for other potentially impacted batches.\u003Cbr>\nc. Documentation of examination and\u002For testing of the bulk drug products.\u003C\u002Fp>\n\n\u003Cp>2. In response to Observation 2 of the Form FDA 483, you state that the “accuracy, specificity, and reproducibility of titration assay method has been initiated and established for ascorbic acid 500mg\u002FmL injection.” However, you did not provide a completed method validation report for the titration assay of ascorbic acid.\u003C\u002Fp>\n\n\u003Cp>3. In response to Observation 3 of the Form FDA 483, you acknowledge that \u003Cstrong>(b)(4)\u003C\u002Fstrong> sampling was missing and that you will improve microbiological \u003Cstrong>(b)(4)\u003C\u002Fstrong> sampling. However, you did not provide an updated copy of your firm’s environmental and personnel monitoring procedures including microbial sampling, alert\u002Faction limits, and routine monitoring activities.\u003C\u002Fp>\n\n\u003Cp>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).]\u003C\u002Fp>\n\n\u003Cp>In addition, regarding observations related to the conditions of section 503B of the FDCA, your corrective actions appear deficient: we have reviewed your facility’s December 2021 report and we note that the report still did not identify all drug products that you compounded during the previous 6-month period (section 503B(b)(2) of the FDCA).\u003C\u002Fp>\n\n\u003Cp>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.\u003C\u002Fp>\n\n\u003Cp>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.\u003C\u002Fp>\n\n\u003Cp>\u003Cstrong>E. Conclusion\u003C\u002Fstrong>\u003C\u002Fp>\n\n\u003Cp>The 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.\u003C\u002Fp>\n\n\u003Cp>You should take prompt action to correct any violations. Failure to adequately address any violations may result in legal action without further notice, including, without limitation, seizure and injunction.\u003C\u002Fp>\n\n\u003Cp>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 any violations, as well as copies of related documentation. If you believe that 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.\u003C\u002Fp>\n\n\u003Cp>Your written notification should refer to case number 629021.\u003C\u002Fp>\n\n\u003Cp>Please electronically submit your reply, on company letterhead, to Shawn Larson, Compliance Officer, at ORAPHARM2_RESPONSES@fda.hhs.gov. In addition, please submit a signed copy of your response to Shawn.Larson@fda.hhs.gov and JoseR.Lopez@fda.hhs.gov.\u003C\u002Fp>\n\n\u003Cp>If you have questions regarding the contents of this letter, you may contact Dr. Larson via phone at 214-253-5216 or email at Shawn.Larson@fda.hhs.gov.\u003C\u002Fp>\n\n\u003Cp>Sincerely,\u003Cbr>\n\u002FS\u002F\u003C\u002Fp>\n\n\u003Cp>Monica R. Maxwell\u003Cbr>\nProgram Division Director\u003Cbr>\nOffice of Pharmaceutical Quality Operations,\u003Cbr>\nDivision II\u003C\u002Fp>\n\n\u003Cp>____________________\u003C\u002Fp>\n\n\u003Cp>\u003Cem>\u003Cstrong>1 \u003C\u002Fstrong>\u003C\u002Fem>See Pub. L. No. 113-54, § 102(a), 127 Stat. 587, 587-588 (2013).\u003C\u002Fp>\n\n\u003Cp>\u003Cem>\u003Cstrong>2\u003C\u002Fstrong>\u003C\u002Fem> We 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.\u003C\u002Fp>\n\n\u003Cp>\u003Cem>\u003Cstrong>3\u003C\u002Fstrong>\u003C\u002Fem> The specific products made by your firm are drugs within the meaning of section 201(g) of the Act, [21 U.S.C. § 321(g)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of diseases and\u002For 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.\u003C\u002Fp>\n\n\u003Cp>\u003Cstrong>4\u003C\u002Fstrong> Your 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).\u003C\u002Fp>\n\n\n\u003C!--BEGIN QUALTRICS WEBSITE FEEDBACK SNIPPET-->\n\u003C!--BEGIN QUALTRICS WEBSITE FEEDBACK SNIPPET-->\n\n\n\n              \n                                            \n              \n            ","Product:\n\nDrugs\n\nRecipient:\n\nRecipient Name\n\nPonswamy Rajalingam, Ph.D.\n\nRecipient Title\n\nOwner and President\n\nHybrid Pharma, LLC\n\n1015 West Newport Center Drive, Suite 106-A\n\nDeerfield Beach, FL 33442-7707\n\nUnited States\n\nIssuing Office:\n\nOffice of Pharmaceutical Quality Operations, Division II\n\nUnited States\n\nDATE: June 7, 2022\n\nCase #: 629021\n\nWARNING LETTER\n\nDr. Rajalingam:\n\nYou 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]1 on January 14, 2015, and most recently on November 24, 2021. From July 27, 2021 to September 3, 2021, an FDA investigator inspected your facility, Hybrid Pharma, LLC, located at 1015 West Newport Center Drive, Suite 106-A, Deerfield Beach, Florida 33442. 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 sterile drug products, which put patients at risk.\n\nFDA issued a Form FDA 483 to your facility on September 3, 2021. FDA acknowledges receipt of your facility’s response, dated September 24, 2021. Based on this inspection, it appears you produced drugs that violate the FDCA.\n\nA. Compounded Drug Products under the FDCA\n\nUnder 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.2\n\nAn 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.\n\nIn addition, for a compounded drug product to qualify for the exemptions under section 503B, it must be compounded in an outsourcing facility that is in compliance with the registration and reporting requirements in section 503B(b) including the requirement to submit a report to FDA upon initially registering as an outsourcing facility, once in June of each year, and once in December of each year identifying the drug products compounded during the previous 6-month period (section 503B(b)(2) of the FDCA [21 U.S.C. §353b(b)(2)]).\n\nB. Failure to Meet the Conditions of Section 503B\n\nDuring 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 collected evidence indicating that your facility failed to submit a complete report to FDA in December 2020 and June 2021, identifying all the drug products that you compounded during the previous 6-month period, including Phosphatidyl choline 5% and deoxycholate 4.2% injectable and (b)(4) Injection (section 503B(b)(2) of the FDCA [21 U.S.C. §353b(b)(2)]).\n\nBecause 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.\n\nSpecific violations are described below.\n\nC. Violations of the FDCA\n\nAdulterated Drug Products\n\nThe FDA investigator 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.\n\nThe violations include, for example:\n\n1. 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).\n\n2. Your firm failed to establish the accuracy, sensitivity, specificity, and reproducibility of its test methods (21 CFR 211.165(e)).\n\n3. Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).\n\nOutsourcing 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.\n\nUnder 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.\n\nUnapproved New Drug Products\n\nYou do not have any FDA-approved applications on file for drug products that you compound.3 Under 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.\n\nMisbranded Drug Products\n\nYou 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.4 The 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.\n\nFailure to Report Drugs\n\nAs noted above, your facility failed to submit a complete report to FDA in December\n\n2020 and again in June 2021, identifying the drug products that you compounded during\n\nthe previous 6-month period (section 503B(b)(2) of the FDCA). The failure to report\n\ndrugs by an entity that is registered with FDA in accordance with section 503B(b) is a\n\nprohibited act under section 301(ccc)(3) of the FDCA [21 U.S.C. § 331(ccc)(3)].\n\nD. Corrective Actions\n\nWe have reviewed your facility’s response to the Form FDA 483.\n\nWe are unable to fully evaluate some of your corrective actions due to lack of adequate supporting documentation:\n\n1. In response to Observation 1 of the Form FDA 483, you state that your investigation was extended to other batches and bulk drug samples were submitted to the manufacturer. However, you did not provide:\n\na. Copies of completed investigation reports.\n\nb. Documentation showing visual inspections were performed for other potentially impacted batches.\n\nc. Documentation of examination and\u002For testing of the bulk drug products.\n\n2. In response to Observation 2 of the Form FDA 483, you state that the “accuracy, specificity, and reproducibility of titration assay method has been initiated and established for ascorbic acid 500mg\u002FmL injection.” However, you did not provide a completed method validation report for the titration assay of ascorbic acid.\n\n3. In response to Observation 3 of the Form FDA 483, you acknowledge that (b)(4) sampling was missing and that you will improve microbiological (b)(4) sampling. However, you did not provide an updated copy of your firm’s environmental and personnel monitoring procedures including microbial sampling, alert\u002Faction limits, and routine monitoring activities.\n\nIn 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).]\n\nIn addition, regarding observations related to the conditions of section 503B of the FDCA, your corrective actions appear deficient: we have reviewed your facility’s December 2021 report and we note that the report still did not identify all drug products that you compounded during the previous 6-month period (section 503B(b)(2) of the FDCA).\n\nShould 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.\n\nFDA 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.\n\nE. Conclusion\n\nThe 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.\n\nYou should take prompt action to correct any violations. Failure to adequately address any violations may result in legal action without further notice, including, without limitation, seizure and injunction.\n\nWithin 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 any violations, as well as copies of related documentation. If you believe that 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.\n\nYour written notification should refer to case number 629021.\n\nPlease electronically submit your reply, on company letterhead, to Shawn Larson, Compliance Officer, at ORAPHARM2_RESPONSES@fda.hhs.gov. In addition, please submit a signed copy of your response to Shawn.Larson@fda.hhs.gov and JoseR.Lopez@fda.hhs.gov.\n\nIf you have questions regarding the contents of this letter, you may contact Dr. Larson via phone at 214-253-5216 or email at Shawn.Larson@fda.hhs.gov.\n\nSincerely,\n\n\u002FS\u002F\n\nMonica R. Maxwell\n\nProgram Division Director\n\nOffice of Pharmaceutical Quality Operations,\n\nDivision II\n\n____________________\n\n1 See Pub. L. No. 113-54, § 102(a), 127 Stat. 587, 587-588 (2013).\n\n2 We 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.\n\n3 The specific products made by your firm are drugs within the meaning of section 201(g) of the Act, [21 U.S.C. § 321(g)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of diseases and\u002For 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.\n\n4 Your 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).","2026-08-20T01:50:18.233+00:00",[22,23,24,9,25,26,26,26],"\u003Ctime datetime=\"2022-06-14T13:20:00Z\">06\u002F14\u002F2022\u003C\u002Ftime>\n","\u003Ctime datetime=\"2022-06-07T04:00:00Z\">06\u002F07\u002F2022\u003C\u002Ftime>\n","\u003Ca href=\"\u002Finspections-compliance-enforcement-and-criminal-investigations\u002Fwarning-letters\u002Fhybrid-pharma-llc-629021-06072022\">Hybrid Pharma, LLC\u003C\u002Fa>","Compounding Pharmacy\u002FAdulterated Drug Products \u003Cbr \u002F>\r\n","","2026-08-18T06:42:29.262718+00:00","2026-08-20T02:24:56.48659+00:00",{"510k":30,"classification":31,"enforcement":32,"event":33,"pma":34,"warning_letter":35},"2026-08-18T06:35:18.347+00:00","2026-08-18T05:52:53.75+00:00","2026-08-18T08:01:54.918+00:00","2026-08-19T02:58:35.995+00:00","2026-08-18T06:36:30.549+00:00","2026-08-20T03:28:02.95+00:00"]