[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"fda-warning-letter-indiana-lions-eye-bank-inc-dba-visionfirst-indiana-lions-eye-bank-680039-06102024":3,"fda-latest-sync-dates":33},{"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":13,"case_status":14,"letter_url":15,"reference_number":16,"marcs_cms_no":17,"product_type":18,"delivery_method":19,"recipient_name":20,"recipient_title":8,"body_html":21,"body_text":22,"body_fetched_at":23,"medical_device_id":8,"raw":24,"created_at":31,"updated_at":32},1403,"indiana-lions-eye-bank-inc-dba-visionfirst-indiana-lions-eye-bank-680039-06102024","Warning Letter","Indiana Lions Eye Bank, Inc. dba VisionFirst Indiana Lions Eye Bank",null,"Division of Biological Products Operations II","Deviations\u002FCFR\u002FRegulations for Human Cells, Tissues & Cellular Products (HCT\u002FPs)","2024-06-25","2024-06-10","2026-02-12","Closed Out","https:\u002F\u002Fwww.fda.gov\u002Finspections-compliance-enforcement-and-criminal-investigations\u002Fwarning-letters\u002Findiana-lions-eye-bank-inc-dba-visionfirst-indiana-lions-eye-bank-680039-06102024","OBPO 24-680039","680039","Biologics","VIA UNITED PARCEL SERVICE SIGNATURE REQUIRED","Timothy M. Fischer","\n\n                            \n                            \n                            \n                            \n                                              \n  \n \n\n                 \n\n  \u003Chr>\n \n\n\u003Cdiv class=\"inset-column\">\n  \u003Cdl class=\"lcds-description-list--grid\">\n\n              \u003Cdt class=\"cell-1_1\">Delivery Method:\u003C\u002Fdt> \n        \u003Cdd class=\"cell-2_1\">VIA UNITED PARCEL SERVICE SIGNATURE REQUIRED\n                                                                                                                                                                                                                                                                                                                                                                                                                              \u003C\u002Fdd>\n      \n              \u003Cdt class=\"cell-1_2\">Reference #:\u003C\u002Fdt> \n        \u003Cdd class=\"cell-2_2\">OBPO 24-680039\u003C\u002Fdd>\n      \n              \u003Cdt class=\"cell-1_3\">Product:\u003C\u002Fdt> \n        \u003Cdd class=\"cell-2_3\">Biologics                          \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\">Timothy M. Fischer\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\">President\u002FChief Executive Officer\u003C\u002Fdiv>\n          \u003C\u002Fdiv>\n\u003C\u002Fdd>\n          \n            \u003Cdd>Indiana Lions Eye Bank, Inc. dba VisionFirst Indiana Lions Eye Bank\u003C\u002Fdd>\n\n          \n                      \u003Cdd>\u003Cp class=\"address\" translate=\"no\">\u003Cspan class=\"address-line1\">4745 Haven Point Blvd.\u003C\u002Fspan>\u003Cbr>\n\u003Cspan class=\"locality\">Carmel\u003C\u002Fspan>, \u003Cspan class=\"administrative-area\">IN\u003C\u002Fspan> \u003Cspan class=\"postal-code\">46280\u003C\u002Fspan>\u003Cbr>\n\u003Cspan class=\"country\">United States\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fdd>\n          \n          \n            \n            \u003Cdd>\u003C!-- Loop this field. For FDA Office content type. Display the Other contact channel is a dd span with an icon-->\n\n    \u003C\u002Fdd>\u003Cdd>\u003Cspan class=\"fa fa-envelope\" aria-hidden=\"true\">\u003C\u002Fspan>\u003Ca href=\"mailto:Tfischer@visionfirst.org\"> Tfischer@visionfirst.org\u003C\u002Fa>\u003C\u002Fdd>\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>Division of Biological Products Operations 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>June 10, 2024\u003C\u002Fp>\n\n\u003Cp class=\"text-align-center\">\u003Cstrong>Warning Letter OBPO 24-680039\u003C\u002Fstrong>\u003C\u002Fp>\n\n\u003Cp>Dear Mr. Fischer:\u003C\u002Fp>\n\n\u003Cp>During an inspection of your firm, Indiana Lions Eye Bank, Inc. dba VisionFirst Indiana Lions Eye Bank, located at 4745 Haven Point Blvd., Carmel, IN, conducted between January 22, 2024, and February 1, 2024, the United States Food and Drug Administration (FDA) documented significant deviations from the regulations for human cells, tissues, and cellular and tissue-based products (HCTPs) set forth in Title 21 Code of Federal Regulations (CFR) Part 1271 (21 CFR 1271) and issued under the authority of Section 361 of the Public Health Service Act [42 U.S.C. § 264].\u003C\u002Fp>\n\n\u003Cp>The deviations documented on the Form FDA-483, List of Inspectional Observations (FDA 483), were presented to and discussed with you at the conclusion of the inspection. These items of concern include, but are not limited to, the following:\u003C\u002Fp>\n\n\u003Cp>\u003Cstrong>1. Failure to determine as ineligible a donor who is identified as having a risk factor for, or clinical evidence of, any of the relevant communicable disease agents or diseases for which screening is required under 21 CFR 1271.75(a)(1) [21 CFR 1271.75(d)].\u003C\u002Fstrong> Between January 2021 and January 2024, you failed to determine as ineligible five donors of ocular HCT\u002FPs with a documented diagnosis or clinical evidence of sepsis, including two or more systemic responses to infection, documented within their available medical records during the hospital stay immediately preceding death. For example:\u003C\u002Fp>\n\n\u003Cp>a. Donor \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong> was determined eligible on 1\u002F11\u002F24 and ocular HCT\u002FPs from the donor were distributed on \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong>.\u003C\u002Fp>\n\n\u003Cp>The donor was initially hospitalized on \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong> with a hospitalization that spanned \u003Cstrong>(b)(4)\u003C\u002Fstrong> across multiple hospitals and was complicated by multiple serious clinical conditions. Given the donor’s age, co-morbidities, deconditioned state, and protracted hospitalization, the donor was at high risk for sepsis. The donor’s health continued to decline, and the donor expired on \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong> with the cause of death attributed to sepsis and septic shock.\u003C\u002Fp>\n\n\u003Cp>This donor with multiple serious medical conditions had risk factors for and clinical evidence of sepsis, and two or more systemic responses to infection documented in the medical records of the hospital stay immediately preceding death based on, but not limited to, the following:\u003C\u002Fp>\n\n\u003Cul>\n\t\u003Cli>Evidence of urinary tract infection (urine culture on 12\u002F10\u002F23 grew \u003Cem>Klebsiella pneumoniae\u003C\u002Fem>);\u003C\u002Fli>\n\t\u003Cli>\u003Cem>Klebsiella pneumoniae\u003C\u002Fem> aspiration pneumonia;\u003C\u002Fli>\n\t\u003Cli>\u003Cem>Clostridioides difficile\u003C\u002Fem> colitis\u003C\u002Fli>\n\t\u003Cli>Respiratory rate >20 breaths\u002Fminute (39 breaths\u002Fminute on 1\u002F5\u002F24); and\u003C\u002Fli>\n\t\u003Cli>Elevated White Blood Cell (WBC) count >12,000 cells\u002Fmm\u003Csup>3\u003C\u002Fsup> (16,700 cells\u002Fmm\u003Csup>3\u003C\u002Fsup> on 1\u002F7\u002F24);\u003C\u002Fli>\n\t\u003Cli>Heart rate >90 beats\u002Fminute (144 beats\u002Fminute on 1\u002F7\u002F24); and\u003C\u002Fli>\n\t\u003Cli>Altered mental status.\u003C\u002Fli>\n\u003C\u002Ful>\n\n\u003Cp>b. Donor \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong> was determined eligible on 1\u002F3\u002F24 and ocular HCT\u002FPs from the donor were distributed on \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong>.\u003C\u002Fp>\n\n\u003Cp>The donor was taken to the Emergency Department (ED) on \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong> and was found to have agitation, confusion, hypotension, hypothermia, and multi-organ failure (heart, lungs, liver, kidneys). The donor was admitted to the Intensive Care Unit (ICU) for shock of mixed etiology (cardiogenic and sepsis, septic shock due to undetermined organism) and possible community acquired versus aspiration pneumonia and was treated with broad spectrum antibiotics. Despite aggressive measures, the donor continued to decline and expired on \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong>. The donor had a diagnosis of septic shock due to bacterial (\u003Cem>Proteus mirabilis\u003C\u002Fem>) and viral (Respiratory Syncytial Virus) pneumonia and clinical evidence of sepsis at the time of death. Both organisms can cause sepsis and special viral culture media, or a PCR test would be necessary to detect RSV in the blood.\u003C\u002Fp>\n\n\u003Cp>Donor \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong> had risk factors for and clinical evidence of sepsis, and two or more systemic responses to infection documented in the medical records of the hospital stay immediately preceding death based on, but not limited to, the following:\u003C\u002Fp>\n\n\u003Cul>\n\t\u003Cli>Heart rate >90 beats\u002Fminute (97 beats\u002Fminute on 12\u002F27\u002F23)\u003C\u002Fli>\n\t\u003Cli>Sputum culture positive for \u003Cem>Proteus mirabilis\u003C\u002Fem> and respiratory specimen positive for RSV (12\u002F28\u002F23);\u003C\u002Fli>\n\t\u003Cli>Elevated procalcitonin level;\u003C\u002Fli>\n\t\u003Cli>Altered mental status;\u003C\u002Fli>\n\t\u003Cli>Lactic acidosis;\u003C\u002Fli>\n\t\u003Cli>Multi-organ failure; and\u003C\u002Fli>\n\t\u003Cli>Oliguria.\u003C\u002Fli>\n\u003C\u002Ful>\n\n\u003Cp>c. Donor \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong> was determined eligible on 12\u002F12\u002F23 and ocular HCT\u002FPs from the donor were distributed on \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong> and \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong>.\u003C\u002Fp>\n\n\u003Cp>The donor was admitted to the ED on \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong> and was noted to have systemic inflammatory response syndrome (SIRS), profound hyperglycemia, leukocytosis, thrombocytopenia, lactic acidosis, acute renal failure, “shock liver” and passive congestion of liver due to right sided heart failure, pericardial effusion, and urosepsis. The donor was given intravenous fluids and vasopressor support and was treated with Vancomycin and Zosyn for “florid septic shock.” The donor was found in asystole and expired on \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong>.\u003C\u002Fp>\n\n\u003Cp>Donor \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong> had a diagnosis of sepsis (urosepsis), risk factors for and clinical evidence of sepsis, and two or more systemic responses to infection documented in the medical records of the hospital stay immediately preceding death based on, but not limited to, the following:\u003C\u002Fp>\n\n\u003Cul>\n\t\u003Cli>Urinary tract infection (urine culture from \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong> grew more than 100,000 cfu\u002FmL of \u003Cem>Klebsiella pneumoniae\u003C\u002Fem>);\u003C\u002Fli>\n\t\u003Cli>Respiratory rate >20 breaths\u002Fminute (27 breaths\u002Fminute on 12\u002F10\u002F23 and acute hypoxic respiratory failure);\u003C\u002Fli>\n\t\u003Cli>Elevated WBC count >12,000 cells\u002Fmm\u003Csup>3\u003C\u002Fsup> (15,600 cells\u002Fmm3 on 12\u002F10\u002F23);\u003C\u002Fli>\n\t\u003Cli>Altered mental status;\u003C\u002Fli>\n\t\u003Cli>Lactic acidosis; and\u003C\u002Fli>\n\t\u003Cli>Multi-organ failure.\u003C\u002Fli>\n\u003C\u002Ful>\n\n\u003Cp>d. Donor \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong> was determined eligible on 4\u002F3\u002F23 and ocular HCT\u002FPs from the donor were distributed on \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong>.\u003C\u002Fp>\n\n\u003Cp>The donor was admitted to the ED from an extended care facility on 3\u002F29\u002F23 with a diagnosis of severe hypoxic respiratory failure, requiring supplemental oxygen, and sepsis due to bilateral pneumonia. The donor expired the same day. The ED record also describes that the donor met SIRS criteria. The discharge summary lists the primary cause of death as respiratory failure with hypoxia, with sepsis listed as a contributing factor.\u003C\u002Fp>\n\n\u003Cp>Donor \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong> had risk factors for and clinical evidence of sepsis, and two or more systemic responses to infection documented in the medical records of the hospital stay immediately preceding death based on, but not limited to, the following:\u003C\u002Fp>\n\n\u003Cul>\n\t\u003Cli>Bilateral pneumonia on chest x-ray (3\u002F29\u002F23);\u003C\u002Fli>\n\t\u003Cli>Severe hypoxic respiratory failure;\u003C\u002Fli>\n\t\u003Cli>Heart rate >90 beats\u002Fminute (126 beats\u002Fminute on 3\u002F29\u002F23); and\u003C\u002Fli>\n\t\u003Cli>Respiratory rate >20 breaths\u002Fminute (31 breaths\u002Fminute on 3\u002F29\u002F23).\u003C\u002Fli>\n\u003C\u002Ful>\n\n\u003Cp>e. Donor \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong> was determined eligible on 4\u002F6\u002F21 and ocular HCT\u002FPs from the donor were distributed on \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong>.\u003C\u002Fp>\n\n\u003Cp>The donor presented in the ED on \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong> and was subsequently admitted to the ICU for “undifferentiated shock” attributed to sepsis and\u002For hypovolemia from dehydration and third spacing of fluid. The donor was treated with multiple renally dosed broad-spectrum antibiotics between \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong> and \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong>, had a diagnosis of undifferentiated shock initially attributed to sepsis versus hypovolemia and, on 3\u002F26\u002F2021, the medical record clearly states that the shock was partly due to sepsis.\u003C\u002Fp>\n\n\u003Cp>While the donor also had colitis and \u003Cem>Brevibacterium sp\u003C\u002Fem>. bacteremia on admission, it is unclear whether the presence of this microorganism in one blood culture was a contaminant or a true pathogen. We note that \u003Cem>Brevibacterium sp\u003C\u002Fem>. has been reported as a cause of sepsis in cancer and immunocompromised patients.\u003Csup>\u003Cem>\u003Cstrong>1-2\u003C\u002Fstrong>\u003C\u002Fem>\u003C\u002Fsup> Although follow-up blood cultures on 3\u002F30\u002F21 showed no growth, the specimens were obtained while the donor was still on antibiotics and the donor clinically decompensated when the antibiotics were discontinued upon withdrawal of care due to the cancer prognosis. On the day of death (\u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong>), the donor showed additional, more severe signs of sepsis.\u003C\u002Fp>\n\n\u003Cp>Donor \u003Cstrong>(b)(6), (b)(7)(C)\u003C\u002Fstrong> had risk factors for and clinical evidence of sepsis, and two or more systemic responses to infection documented in the medical records of the hospital stay immediately preceding death based on, but not limited to, the following:\u003C\u002Fp>\n\n\u003Cul>\n\t\u003Cli>Heart rate >90 beats\u002Fminute (114 beats\u002Fminute on 3\u002F27\u002F21)\u003C\u002Fli>\n\t\u003Cli>Diagnosis of a urinary tract infection on 3\u002F29\u002F21;\u003C\u002Fli>\n\t\u003Cli>Respiratory rate >20 breaths\u002Fminute (24 breaths\u002Fminute on 3\u002F29\u002F21);\u003C\u002Fli>\n\t\u003Cli>Elevated WBC count >12,000 cells\u002Fmm3 (24,400 cells\u002Fmm3 on 3\u002F30\u002F21);\u003C\u002Fli>\n\t\u003Cli>Elevated lactate (lactic acidosis);\u003C\u002Fli>\n\t\u003Cli>Altered mental status;\u003C\u002Fli>\n\t\u003Cli>Hypoxia with high FiO2 requirements;\u003C\u002Fli>\n\t\u003Cli>Oliguria; and\u003C\u002Fli>\n\t\u003Cli>Multi-organ system failure.\u003C\u002Fli>\n\u003C\u002Ful>\n\n\u003Cp>The events described above are HCT\u002FP deviations related to core Current Good Tissue Practice (CGTP) requirements and must be investigated and documented. Because these situations represent an HCT\u002FP deviation relating to a core CGTP and to the prevention of communicable disease transmission or HCT\u002FP contamination; and HCT\u002FPs were distributed, deviation reports must be submitted to FDA in accordance with 21 CFR 1271.350(b).\u003C\u002Fp>\n\n\u003Cp>\u003Cstrong>2. Failure to ensure procedures are in compliance with the donor eligibility requirements within Subpart C – Donor Eligibility of 21 CFR 1271 [21 CFR 1271.47(a)].\u003C\u002Fstrong> For example, your procedure, “SOP-DC-1, Transplant Tissue Exclusionary Criteria” (Revision 15, Implementation Date 11\u002F29\u002F22), used to determine donor eligibility and “Form F-DC-25 Sepsis Consult Flowchart” (Revision 1, Implementation Date 03\u002F14\u002F19), used to determine if an infectious disease consult is required, fail to include all clinical evidence and systemic responses to infection, if unexplained, of sepsis during the donor’s hospital stay immediately preceding death to appropriately evaluate a donor’s sepsis risk. Additionally, your “Form F-DC-25 Sepsis Consult Flowchart” includes just two systemic responses to infection (fever >100.4 F and WBC >12,000 cells\u002Fmm\u003Csup>3\u003C\u002Fsup> or <4,000 or bands >10%) that accompany clinical evidence of infection. The flowchart fails to include a heart rate >90 beats\u002Fminute and respiratory rate >20 breaths\u002Fminute or partial pressure of carbon dioxide (PaCO\u003Csub>2\u003C\u002Fsub>) ˂32.\u003Csup>3\u003C\u002Fsup> Finally, your procedure and flowchart fail to include more severe signs of sepsis, such as unexplained hypoxemia, elevated lactate, oliguria, altered mentation, and hypotension.\u003C\u002Fp>\n\n\u003Cp>All five donors referenced above were evaluated for a risk of sepsis using the “Form F-DC-25 Sepsis Consult Flowchart.” Documentation in all the donor records included the following standard statement that failed to take into account all the clinical evidence of sepsis and systemic responses to infection as documented in the medical records during the hospital stay immediately preceding death:\u003C\u002Fp>\n\n\u003Cp>“As long as these were all the clinical ID tests drawn (blood, sputum, urine, peritoneal fluid, CSF, AFB Cxs; viral tests; Quantiferon, etc) there was no definitive empirical evidence of sepsis or bacteremia at TOD.”\u003C\u002Fp>\n\n\u003Cp>The deviations identified above are not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to ensure that your establishment complies with all applicable federal regulations. You are responsible for reviewing your firm’s operations as a whole to ensure that you are in compliance with the law.\u003C\u002Fp>\n\n\u003Cp>We acknowledge receipt of your letter, dated February 23, 2024, providing a response and corrective actions to the FDA’s inspectional observations. We have reviewed your response and we have determined that the response is inadequate to address our concerns. We have the following comments regarding your FDA 483 response and your firm’s corrective actions.\u003C\u002Fp>\n\n\u003Cp>1. In response to Observation 1, your disagreement that the donors were septic at the time of death does not account for the donors’ medical records with documented diagnoses and clinical evidence of sepsis, including systemic responses to infection, during their hospital stay immediately preceding death. Your response states, “there is still only one gold standard for the diagnosis of sepsis, and that is a positive blood culture” and that the blood cultures were negative, and sepsis was thus ruled out for all donors cited on the FDA 483.\u003C\u002Fp>\n\n\u003Cp>Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.\u003Csup>\u003Cem>\u003Cstrong>3-4\u003C\u002Fstrong>\u003C\u002Fem>\u003C\u002Fsup> A diagnosis of sepsis can be made in the emergency room and positive blood cultures are not required for the diagnosis of sepsis.\u003Csup>\u003Cem>\u003Cstrong>3-4\u003C\u002Fstrong>\u003C\u002Fem>\u003C\u002Fsup> Positive pre-mortem blood cultures \u003Cu>\u003Cstrong>may\u003C\u002Fstrong>\u003C\u002Fu> be associated with clinical evidence of sepsis. However, negative blood cultures do not exclude a diagnosis of bacteremia or sepsis. Routine blood cultures do not identify all microbial agents that can cause sepsis and additional incubation time, or special media is sometimes needed. Previous administration of antibiotics is frequently a reason for negative blood cultures (i.e., culture negative sepsis).\u003Csup>\u003Cem>\u003Cstrong>5\u003C\u002Fstrong>\u003C\u002Fem>\u003C\u002Fsup> There are a myriad of reasons why blood cultures may be negative in cases of sepsis and the absence of a positive blood culture does not exclude sepsis as a cause of death.\u003C\u002Fp>\n\n\u003Cp>Additionally, in FDA’s \u003Cem>Guidance for Industry: Eligibility Determination of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT\u002FPs) \u003C\u002Fem>(August 2007), the Agency describes our current thinking on the risks of sepsis in deceased donors to include a review of medical records during a hospital stay immediately preceding death for diagnosis of sepsis, clinical evidence of infection, and systemic responses to infection. These risk factors for sepsis and septic shock are supported in recent medical literature.\u003Csup>\u003Cem>\u003Cstrong>3-4\u003C\u002Fstrong>\u003C\u002Fem>\u003C\u002Fsup>\u003C\u002Fp>\n\n\u003Cp>2. In response to Observation 3, we acknowledge that you have revised your procedure, “SOP-DC-1 Transplant Tissue Exclusionary Criteria,” to include reference to “Form F-DC-25 Sepsis Assessment Flowchart” and have revised section 6.4.11 as “Persons who have a documented medical diagnosis of sepsis immediately preceding death, or have documented clinical evidence consistent with a diagnosis of sepsis, which is not explained by other clinical conditions at the time of death.” However, your revised procedure does not account for the diagnosis or clinical evidence of sepsis, including systemic responses to infection, during a hospital stay immediately preceding death.\u003C\u002Fp>\n\n\u003Cp>We also acknowledge that you have revised “Form F-DC-25 Sepsis Assessment Flowchart” to include additional systemic responses to infection such as elevated heart rate and respiratory rate. However, it fails to include additional severe signs of sepsis described above that were also missing from your revised procedure. In addition, the flowchart states, “Complete for donors, with transplant intent, that were diagnosed or had a suspicion of sepsis, or positive blood cultures noted in the donor’s available records within five (5) days of death.” We note that a donor must be determined ineligible if there is documented diagnosis and clinical evidence of sepsis, including systemic responses to infection, documented in their medical records during a hospital stay immediately preceding death regardless of whether that information is documented within five days of death.\u003C\u002Fp>\n\n\u003Cp>You should take prompt action to correct the violations addressed in this letter and prevent their recurrence. Failure to promptly correct these violations may result in regulatory action being initiated by the FDA without further notice.\u003C\u002Fp>\n\n\u003Cp>We request that you respond in writing within fifteen (15) working days from your receipt of this letter, outlining the specific steps you have taken or plan to take to correct the noted violations, including an explanation of how you plan to prevent these violations, or similar violations, from occurring again. If you believe that your products are not in violation of the law, include your reasoning and any supporting information for our consideration. Additionally, include any documentation necessary to show that correction has been achieved. If you cannot complete all corrective actions within fifteen (15) working days, please explain the reason for your delay and the timeframe within which the remaining corrections will be completed.\u003C\u002Fp>\n\n\u003Cp>Your response should be sent to the following address: Young Mi Yoon, Compliance Officer, U.S. Food & Drug Administration, Office of Biological Products Operations – Division 2, 222 W. 7th Avenue, #25, Room 122, Anchorage, AK 99513 or emailed to YoungMi.Yoon@fda.hhs.gov. If you should have any questions, please contact Young Mi Yoon, Compliance Officer at (907) 248-8146 x 104 or via e-mail.\u003C\u002Fp>\n\n\u003Cp>Sincerely,\u003Cbr>\n\u002FS\u002F\u003C\u002Fp>\n\n\u003Cp>Karlton T. Watson\u003Cbr>\nProgram Division Director\u003Cbr>\nOffice of Biological Products Operations – Division 2\u003C\u002Fp>\n\n\u003Cp>_________________________\u003C\u002Fp>\n\n\u003Cp>\u003Cem>\u003Cstrong>1\u003C\u002Fstrong>\u003C\u002Fem> Castagnola, E. et al. Broviac catheter-related bacteraemias due to unusual pathogens in children with cancer: case reports with literature review. J Infect. 1997 May; 34(3): 215-8.\u003C\u002Fp>\n\n\u003Cp>\u003Cem>\u003Cstrong>2\u003C\u002Fstrong>\u003C\u002Fem> Lina, B. Persistent bacteremia due to Brevibacterium species in an immunocompromised patient. Clin Infect Dis. 1994 Mar;18(3): 487-8.\u003C\u002Fp>\n\n\u003Cp>\u003Cem>\u003Cstrong>3\u003C\u002Fstrong>\u003C\u002Fem> Singer M, Deutschman CS, Seymour CW, et al: The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016; 315:801–810.\u003C\u002Fp>\n\n\u003Cp>\u003Cem>\u003Cstrong>4\u003C\u002Fstrong>\u003C\u002Fem> Evans, L. et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021 Nov 1;49(11): e1063-e1143\u003C\u002Fp>\n\n\u003Cp>\u003Cstrong>5\u003C\u002Fstrong> Scheer, CS. Impact of antibiotic administration on blood culture positivity at the beginning of sepsis: a prospective clinical cohort study. Clin Microbiol Infect. 2019 Mar; 25(3):326-331.\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            ","Delivery Method:\n\nVIA UNITED PARCEL SERVICE SIGNATURE REQUIRED\n\nReference #:\n\nOBPO 24-680039\n\nProduct:\n\nBiologics\n\nRecipient:\n\nRecipient Name\n\nTimothy M. Fischer\n\nRecipient Title\n\nPresident\u002FChief Executive Officer\n\nIndiana Lions Eye Bank, Inc. dba VisionFirst Indiana Lions Eye Bank\n\n4745 Haven Point Blvd.\n\nCarmel, IN 46280\n\nUnited States\n\nTfischer@visionfirst.org\n\nIssuing Office:\n\nDivision of Biological Products Operations II\n\nUnited States\n\nJune 10, 2024\n\nWarning Letter OBPO 24-680039\n\nDear Mr. Fischer:\n\nDuring an inspection of your firm, Indiana Lions Eye Bank, Inc. dba VisionFirst Indiana Lions Eye Bank, located at 4745 Haven Point Blvd., Carmel, IN, conducted between January 22, 2024, and February 1, 2024, the United States Food and Drug Administration (FDA) documented significant deviations from the regulations for human cells, tissues, and cellular and tissue-based products (HCTPs) set forth in Title 21 Code of Federal Regulations (CFR) Part 1271 (21 CFR 1271) and issued under the authority of Section 361 of the Public Health Service Act [42 U.S.C. § 264].\n\nThe deviations documented on the Form FDA-483, List of Inspectional Observations (FDA 483), were presented to and discussed with you at the conclusion of the inspection. These items of concern include, but are not limited to, the following:\n\n1. Failure to determine as ineligible a donor who is identified as having a risk factor for, or clinical evidence of, any of the relevant communicable disease agents or diseases for which screening is required under 21 CFR 1271.75(a)(1) [21 CFR 1271.75(d)]. Between January 2021 and January 2024, you failed to determine as ineligible five donors of ocular HCT\u002FPs with a documented diagnosis or clinical evidence of sepsis, including two or more systemic responses to infection, documented within their available medical records during the hospital stay immediately preceding death. For example:\n\na. Donor (b)(6), (b)(7)(C) was determined eligible on 1\u002F11\u002F24 and ocular HCT\u002FPs from the donor were distributed on (b)(6), (b)(7)(C).\n\nThe donor was initially hospitalized on (b)(6), (b)(7)(C) with a hospitalization that spanned (b)(4) across multiple hospitals and was complicated by multiple serious clinical conditions. Given the donor’s age, co-morbidities, deconditioned state, and protracted hospitalization, the donor was at high risk for sepsis. The donor’s health continued to decline, and the donor expired on (b)(6), (b)(7)(C) with the cause of death attributed to sepsis and septic shock.\n\nThis donor with multiple serious medical conditions had risk factors for and clinical evidence of sepsis, and two or more systemic responses to infection documented in the medical records of the hospital stay immediately preceding death based on, but not limited to, the following:\n\nEvidence of urinary tract infection (urine culture on 12\u002F10\u002F23 grew Klebsiella pneumoniae);\n\nKlebsiella pneumoniae aspiration pneumonia;\n\nClostridioides difficile colitis\n\nRespiratory rate >20 breaths\u002Fminute (39 breaths\u002Fminute on 1\u002F5\u002F24); and\n\nElevated White Blood Cell (WBC) count >12,000 cells\u002Fmm3 (16,700 cells\u002Fmm3 on 1\u002F7\u002F24);\n\nHeart rate >90 beats\u002Fminute (144 beats\u002Fminute on 1\u002F7\u002F24); and\n\nAltered mental status.\n\nb. Donor (b)(6), (b)(7)(C) was determined eligible on 1\u002F3\u002F24 and ocular HCT\u002FPs from the donor were distributed on (b)(6), (b)(7)(C).\n\nThe donor was taken to the Emergency Department (ED) on (b)(6), (b)(7)(C) and was found to have agitation, confusion, hypotension, hypothermia, and multi-organ failure (heart, lungs, liver, kidneys). The donor was admitted to the Intensive Care Unit (ICU) for shock of mixed etiology (cardiogenic and sepsis, septic shock due to undetermined organism) and possible community acquired versus aspiration pneumonia and was treated with broad spectrum antibiotics. Despite aggressive measures, the donor continued to decline and expired on (b)(6), (b)(7)(C). The donor had a diagnosis of septic shock due to bacterial (Proteus mirabilis) and viral (Respiratory Syncytial Virus) pneumonia and clinical evidence of sepsis at the time of death. Both organisms can cause sepsis and special viral culture media, or a PCR test would be necessary to detect RSV in the blood.\n\nDonor (b)(6), (b)(7)(C) had risk factors for and clinical evidence of sepsis, and two or more systemic responses to infection documented in the medical records of the hospital stay immediately preceding death based on, but not limited to, the following:\n\nHeart rate >90 beats\u002Fminute (97 beats\u002Fminute on 12\u002F27\u002F23)\n\nSputum culture positive for Proteus mirabilis and respiratory specimen positive for RSV (12\u002F28\u002F23);\n\nElevated procalcitonin level;\n\nAltered mental status;\n\nLactic acidosis;\n\nMulti-organ failure; and\n\nOliguria.\n\nc. Donor (b)(6), (b)(7)(C) was determined eligible on 12\u002F12\u002F23 and ocular HCT\u002FPs from the donor were distributed on (b)(6), (b)(7)(C) and (b)(6), (b)(7)(C).\n\nThe donor was admitted to the ED on (b)(6), (b)(7)(C) and was noted to have systemic inflammatory response syndrome (SIRS), profound hyperglycemia, leukocytosis, thrombocytopenia, lactic acidosis, acute renal failure, “shock liver” and passive congestion of liver due to right sided heart failure, pericardial effusion, and urosepsis. The donor was given intravenous fluids and vasopressor support and was treated with Vancomycin and Zosyn for “florid septic shock.” The donor was found in asystole and expired on (b)(6), (b)(7)(C).\n\nDonor (b)(6), (b)(7)(C) had a diagnosis of sepsis (urosepsis), risk factors for and clinical evidence of sepsis, and two or more systemic responses to infection documented in the medical records of the hospital stay immediately preceding death based on, but not limited to, the following:\n\nUrinary tract infection (urine culture from (b)(6), (b)(7)(C) grew more than 100,000 cfu\u002FmL of Klebsiella pneumoniae);\n\nRespiratory rate >20 breaths\u002Fminute (27 breaths\u002Fminute on 12\u002F10\u002F23 and acute hypoxic respiratory failure);\n\nElevated WBC count >12,000 cells\u002Fmm3 (15,600 cells\u002Fmm3 on 12\u002F10\u002F23);\n\nAltered mental status;\n\nLactic acidosis; and\n\nMulti-organ failure.\n\nd. Donor (b)(6), (b)(7)(C) was determined eligible on 4\u002F3\u002F23 and ocular HCT\u002FPs from the donor were distributed on (b)(6), (b)(7)(C).\n\nThe donor was admitted to the ED from an extended care facility on 3\u002F29\u002F23 with a diagnosis of severe hypoxic respiratory failure, requiring supplemental oxygen, and sepsis due to bilateral pneumonia. The donor expired the same day. The ED record also describes that the donor met SIRS criteria. The discharge summary lists the primary cause of death as respiratory failure with hypoxia, with sepsis listed as a contributing factor.\n\nDonor (b)(6), (b)(7)(C) had risk factors for and clinical evidence of sepsis, and two or more systemic responses to infection documented in the medical records of the hospital stay immediately preceding death based on, but not limited to, the following:\n\nBilateral pneumonia on chest x-ray (3\u002F29\u002F23);\n\nSevere hypoxic respiratory failure;\n\nHeart rate >90 beats\u002Fminute (126 beats\u002Fminute on 3\u002F29\u002F23); and\n\nRespiratory rate >20 breaths\u002Fminute (31 breaths\u002Fminute on 3\u002F29\u002F23).\n\ne. Donor (b)(6), (b)(7)(C) was determined eligible on 4\u002F6\u002F21 and ocular HCT\u002FPs from the donor were distributed on (b)(6), (b)(7)(C).\n\nThe donor presented in the ED on (b)(6), (b)(7)(C) and was subsequently admitted to the ICU for “undifferentiated shock” attributed to sepsis and\u002For hypovolemia from dehydration and third spacing of fluid. The donor was treated with multiple renally dosed broad-spectrum antibiotics between (b)(6), (b)(7)(C) and (b)(6), (b)(7)(C), had a diagnosis of undifferentiated shock initially attributed to sepsis versus hypovolemia and, on 3\u002F26\u002F2021, the medical record clearly states that the shock was partly due to sepsis.\n\nWhile the donor also had colitis and Brevibacterium sp. bacteremia on admission, it is unclear whether the presence of this microorganism in one blood culture was a contaminant or a true pathogen. We note that Brevibacterium sp. has been reported as a cause of sepsis in cancer and immunocompromised patients.1-2 Although follow-up blood cultures on 3\u002F30\u002F21 showed no growth, the specimens were obtained while the donor was still on antibiotics and the donor clinically decompensated when the antibiotics were discontinued upon withdrawal of care due to the cancer prognosis. On the day of death ((b)(6), (b)(7)(C)), the donor showed additional, more severe signs of sepsis.\n\nDonor (b)(6), (b)(7)(C) had risk factors for and clinical evidence of sepsis, and two or more systemic responses to infection documented in the medical records of the hospital stay immediately preceding death based on, but not limited to, the following:\n\nHeart rate >90 beats\u002Fminute (114 beats\u002Fminute on 3\u002F27\u002F21)\n\nDiagnosis of a urinary tract infection on 3\u002F29\u002F21;\n\nRespiratory rate >20 breaths\u002Fminute (24 breaths\u002Fminute on 3\u002F29\u002F21);\n\nElevated WBC count >12,000 cells\u002Fmm3 (24,400 cells\u002Fmm3 on 3\u002F30\u002F21);\n\nElevated lactate (lactic acidosis);\n\nAltered mental status;\n\nHypoxia with high FiO2 requirements;\n\nOliguria; and\n\nMulti-organ system failure.\n\nThe events described above are HCT\u002FP deviations related to core Current Good Tissue Practice (CGTP) requirements and must be investigated and documented. Because these situations represent an HCT\u002FP deviation relating to a core CGTP and to the prevention of communicable disease transmission or HCT\u002FP contamination; and HCT\u002FPs were distributed, deviation reports must be submitted to FDA in accordance with 21 CFR 1271.350(b).\n\n2. Failure to ensure procedures are in compliance with the donor eligibility requirements within Subpart C – Donor Eligibility of 21 CFR 1271 [21 CFR 1271.47(a)]. For example, your procedure, “SOP-DC-1, Transplant Tissue Exclusionary Criteria” (Revision 15, Implementation Date 11\u002F29\u002F22), used to determine donor eligibility and “Form F-DC-25 Sepsis Consult Flowchart” (Revision 1, Implementation Date 03\u002F14\u002F19), used to determine if an infectious disease consult is required, fail to include all clinical evidence and systemic responses to infection, if unexplained, of sepsis during the donor’s hospital stay immediately preceding death to appropriately evaluate a donor’s sepsis risk. Additionally, your “Form F-DC-25 Sepsis Consult Flowchart” includes just two systemic responses to infection (fever >100.4 F and WBC >12,000 cells\u002Fmm3 or \u003C4,000 or bands >10%) that accompany clinical evidence of infection. The flowchart fails to include a heart rate >90 beats\u002Fminute and respiratory rate >20 breaths\u002Fminute or partial pressure of carbon dioxide (PaCO2) ˂32.3 Finally, your procedure and flowchart fail to include more severe signs of sepsis, such as unexplained hypoxemia, elevated lactate, oliguria, altered mentation, and hypotension.\n\nAll five donors referenced above were evaluated for a risk of sepsis using the “Form F-DC-25 Sepsis Consult Flowchart.” Documentation in all the donor records included the following standard statement that failed to take into account all the clinical evidence of sepsis and systemic responses to infection as documented in the medical records during the hospital stay immediately preceding death:\n\n“As long as these were all the clinical ID tests drawn (blood, sputum, urine, peritoneal fluid, CSF, AFB Cxs; viral tests; Quantiferon, etc) there was no definitive empirical evidence of sepsis or bacteremia at TOD.”\n\nThe deviations identified above are not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to ensure that your establishment complies with all applicable federal regulations. You are responsible for reviewing your firm’s operations as a whole to ensure that you are in compliance with the law.\n\nWe acknowledge receipt of your letter, dated February 23, 2024, providing a response and corrective actions to the FDA’s inspectional observations. We have reviewed your response and we have determined that the response is inadequate to address our concerns. We have the following comments regarding your FDA 483 response and your firm’s corrective actions.\n\n1. In response to Observation 1, your disagreement that the donors were septic at the time of death does not account for the donors’ medical records with documented diagnoses and clinical evidence of sepsis, including systemic responses to infection, during their hospital stay immediately preceding death. Your response states, “there is still only one gold standard for the diagnosis of sepsis, and that is a positive blood culture” and that the blood cultures were negative, and sepsis was thus ruled out for all donors cited on the FDA 483.\n\nSepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.3-4 A diagnosis of sepsis can be made in the emergency room and positive blood cultures are not required for the diagnosis of sepsis.3-4 Positive pre-mortem blood cultures may be associated with clinical evidence of sepsis. However, negative blood cultures do not exclude a diagnosis of bacteremia or sepsis. Routine blood cultures do not identify all microbial agents that can cause sepsis and additional incubation time, or special media is sometimes needed. Previous administration of antibiotics is frequently a reason for negative blood cultures (i.e., culture negative sepsis).5 There are a myriad of reasons why blood cultures may be negative in cases of sepsis and the absence of a positive blood culture does not exclude sepsis as a cause of death.\n\nAdditionally, in FDA’s Guidance for Industry: Eligibility Determination of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT\u002FPs) (August 2007), the Agency describes our current thinking on the risks of sepsis in deceased donors to include a review of medical records during a hospital stay immediately preceding death for diagnosis of sepsis, clinical evidence of infection, and systemic responses to infection. These risk factors for sepsis and septic shock are supported in recent medical literature.3-4\n\n2. In response to Observation 3, we acknowledge that you have revised your procedure, “SOP-DC-1 Transplant Tissue Exclusionary Criteria,” to include reference to “Form F-DC-25 Sepsis Assessment Flowchart” and have revised section 6.4.11 as “Persons who have a documented medical diagnosis of sepsis immediately preceding death, or have documented clinical evidence consistent with a diagnosis of sepsis, which is not explained by other clinical conditions at the time of death.” However, your revised procedure does not account for the diagnosis or clinical evidence of sepsis, including systemic responses to infection, during a hospital stay immediately preceding death.\n\nWe also acknowledge that you have revised “Form F-DC-25 Sepsis Assessment Flowchart” to include additional systemic responses to infection such as elevated heart rate and respiratory rate. However, it fails to include additional severe signs of sepsis described above that were also missing from your revised procedure. In addition, the flowchart states, “Complete for donors, with transplant intent, that were diagnosed or had a suspicion of sepsis, or positive blood cultures noted in the donor’s available records within five (5) days of death.” We note that a donor must be determined ineligible if there is documented diagnosis and clinical evidence of sepsis, including systemic responses to infection, documented in their medical records during a hospital stay immediately preceding death regardless of whether that information is documented within five days of death.\n\nYou should take prompt action to correct the violations addressed in this letter and prevent their recurrence. Failure to promptly correct these violations may result in regulatory action being initiated by the FDA without further notice.\n\nWe request that you respond in writing within fifteen (15) working days from your receipt of this letter, outlining the specific steps you have taken or plan to take to correct the noted violations, including an explanation of how you plan to prevent these violations, or similar violations, from occurring again. If you believe that your products are not in violation of the law, include your reasoning and any supporting information for our consideration. Additionally, include any documentation necessary to show that correction has been achieved. If you cannot complete all corrective actions within fifteen (15) working days, please explain the reason for your delay and the timeframe within which the remaining corrections will be completed.\n\nYour response should be sent to the following address: Young Mi Yoon, Compliance Officer, U.S. Food & Drug Administration, Office of Biological Products Operations – Division 2, 222 W. 7th Avenue, #25, Room 122, Anchorage, AK 99513 or emailed to YoungMi.Yoon@fda.hhs.gov. If you should have any questions, please contact Young Mi Yoon, Compliance Officer at (907) 248-8146 x 104 or via e-mail.\n\nSincerely,\n\n\u002FS\u002F\n\nKarlton T. Watson\n\nProgram Division Director\n\nOffice of Biological Products Operations – Division 2\n\n_________________________\n\n1 Castagnola, E. et al. Broviac catheter-related bacteraemias due to unusual pathogens in children with cancer: case reports with literature review. J Infect. 1997 May; 34(3): 215-8.\n\n2 Lina, B. Persistent bacteremia due to Brevibacterium species in an immunocompromised patient. Clin Infect Dis. 1994 Mar;18(3): 487-8.\n\n3 Singer M, Deutschman CS, Seymour CW, et al: The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016; 315:801–810.\n\n4 Evans, L. et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021 Nov 1;49(11): e1063-e1143\n\n5 Scheer, CS. Impact of antibiotic administration on blood culture positivity at the beginning of sepsis: a prospective clinical cohort study. Clin Microbiol Infect. 2019 Mar; 25(3):326-331.","2026-08-20T00:00:39.048+00:00",[25,26,27,9,28,29,30,29],"\u003Ctime datetime=\"2024-06-25T13:20:00Z\">06\u002F25\u002F2024\u003C\u002Ftime>\n","\u003Ctime datetime=\"2024-06-10T04:00:00Z\">06\u002F10\u002F2024\u003C\u002Ftime>\n","\u003Ca href=\"\u002Finspections-compliance-enforcement-and-criminal-investigations\u002Fwarning-letters\u002Findiana-lions-eye-bank-inc-dba-visionfirst-indiana-lions-eye-bank-680039-06102024\">Indiana Lions Eye Bank, Inc. dba VisionFirst Indiana Lions Eye Bank\u003C\u002Fa>","Deviations\u002FCFR\u002FRegulations for Human Cells, Tissues & Cellular Products (HCT\u002FPs)","","\u003Ca href=\"\u002Finspections-compliance-enforcement-and-criminal-investigations\u002Fwarning-letters\u002Findiana-lions-eye-bank-inc-dba-visionfirst-indiana-lions-eye-bank-680039-02092026\">\u003Ctime datetime=\"2026-02-12T05:00:00Z\">02\u002F12\u002F2026\u003C\u002Ftime>\n\u003C\u002Fa>","2026-08-18T06:42:28.856152+00:00","2026-08-20T02:24:56.037289+00:00",{"510k":34,"classification":35,"enforcement":36,"event":37,"pma":38,"warning_letter":39},"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"]