WARNING LETTER
Lovelace Biomedical Research Institute MARCS-CMS 725136 —
- Delivery Method:
- VIA UNITED PARCEL SERVICE AND VIA E-MAIL
- Product:
- Drugs
- Recipient:
-
Recipient NameRobert W. Rubin
-
Recipient TitleCEO
- Lovelace Biomedical Research Institute
2425 Ridgecrest Drive SE
Albuquerque, NM 87108
United States
- Issuing Office:
- Center for Drug Evaluation and Research (CDER)
United States
WARNING LETTER
FDA Ref. No.: 27-HFD-45-10-01
Dear Mr. Rubin:
This Warning Letter informs you of objectionable conditions observed during the U.S. Food and Drug Administration (FDA) inspection conducted at Lovelace Biomedical Research Institute (LBRI) between April 7 and 18, 2025. The investigator representing FDA reviewed the role of LBRI as the testing facility for the following nonclinical laboratory studies:
- Protocol (b)(4): “(b)(4),” of the investigational drug (b)(4), performed for (b)(4)
- 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 the quality and integrity of study data, in accordance with Title 21 of the Code of Federal Regulations, part 58 (21 CFR 58), Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies.
At the conclusion of the inspection, the FDA investigator presented and discussed with you the Form FDA 483, Inspectional Observations. We acknowledge receipt of your May 9, 2025, 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 May 9, 2025, 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 21 CFR 58 governing the conduct of nonclinical laboratory studies. We wish to emphasize the following:
Failure of the quality assurance unit (QAU) to review the final study report to [en]sure that the reported results accurately reflect the raw data of the nonclinical laboratory study [21 CFR 58.35(b)(6)].
The QAU must review the final study report to ensure that the reported results accurately reflect the raw data of the nonclinical laboratory study. The QAU at your testing facility did not adhere to these requirements.
Specifically, for Protocol (b)(4), the following observations found in the raw data were not documented in the final study report:
1. For 20 out of 34 animals, the final study report did not include all the abnormal cageside clinical observations that were documented between October 1 and January 3, 2024, including but not limited to sneezing; runny or bloody nose; liquid, loose, mucoid, or semisolid stool; sunken eyes; swollen perineum; bloating; hunched posture; low appetite; and heavy breathing.
2. The final study report did not include descriptions of the following dosing issues, which were recorded on the raw data forms for Intravenous Dosing and Blood Collection:
a. Animal 3002, during dosing on October 16, 2023, laid on the cage bottom for one hour and ten minutes after infusion of the test article.
b. Animals 3004 and 3005, during dosing on October 16, 2023, pulled out their venous catheters during infusion of the test article.
c. Animals 1003 and 1004, during dosing on November 1, 2023, pulled out their venous catheters during infusion of the control article.
d. Animal 4005, during dosing on November 11, 2023, had infiltration of the test article into the surrounding tissue of the left saphenous vein.
Specifically, for Protocol (b)(4), the following concerns and observations noted in the raw data were not documented in the final study report:
3. The final study report did not include all the abnormal cageside clinical observations for all 48 animals, documented between November 21, 2022, and July 13, 2023, including incidences of abnormal stool observations, such as bloody or dark-red, liquid, loose, mucoid, or unformed stools.
4. The final study report did not include descriptions of the following dosing issues, which were recorded on the raw data forms for Inhalation Exposure and PK Blood Collection:
a. Animal 2006, during dosing on January 10, 2023, had irregular breathing from the aerosol dosing system during the last few minutes of dosing.
b. Animal 5008, during dosing on April 2, 2023, had irregular breathing and was removed from the aerosol dosing system intermittently.
c. Animal 2004, during dosing on April 5, 2023, had irregular breathing and was removed from the aerosol dosing system after the first 30 minutes of the dose exposure.
d. Animal 3004, on June 14, 2023, was not dosed due to a swollen muzzle.
We acknowledge that this finding as described above was not included on the Form FDA 483 you received, and therefore your written response did not directly address the violation as discussed in this letter.
In your May 9, 2025, written response to the Form FDA 483, regarding the abnormal cageside clinical observations, you stated that documentation of the review of Animal Management System records would be added to the study file, and an addendum would be added to the final study reports for Protocols (b)(4) and (b)(4) by May 31, 2025. You also stated that SOP-1106 (Preparation of a Final Report) and SOP-1882 (Animal Records and Animal Study Data Maintained at LBRI) would be updated by June 15, 2025. Regarding the individual dosing-related issues, your written response acknowledged that the final reports did not specifically discuss individual dosing issues. You stated that documentation of the review of those issues would be added to the study file and an addendum would be added to the final reports, as appropriate, by May 31, 2025. We acknowledge receipt of the revised final study reports, both of which were dated May 30, 2025.
While we acknowledge the corrective and preventive actions that your testing facility has taken and plans to take, your response is inadequate because you did not include sufficient details about your corrective action plan. Specifically, you did not provide sufficient details regarding the updated SOPs, including the nature of the proposed or completed updates. Your corrective action plan also did not include any training on the updated SOPs or on FDA regulations governing the conduct of nonclinical laboratory studies, including the QAU’s role and responsibilities. In addition, the revised final study reports did not completely address the individual dosing issues. Finally, your corrective action plan did not include a description of any planned audits to check for compliance with updated procedures, as applicable. Without these details, we are unable to determine whether your corrective actions are adequate to prevent similar violations in the future.
Because the testing facility’s QAU failed to ensure that the reported results in the final study report accurately reflected the raw data of the nonclinical laboratory studies, FDA is concerned about the integrity of the data generated and reported from nonclinical studies conducted at your testing facility.
We emphasize that as a testing facility conducting nonclinical laboratory studies under 21 CFR 58, you are responsible for ensuring that nonclinical laboratory studies submitted to FDA are conducted and reported in accordance with FDA regulations to ensure the quality and integrity of study data. Your failure to conduct and report nonclinical studies in accordance with FDA regulations raises concerns about the validity and integrity of the data collected at your site.
This letter is not intended to be an all-inclusive list of deficiencies with the nonclinical laboratory studies of investigational drugs conducted at your testing facility. 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 address this matter adequately may lead to regulatory action without further notice to you. 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.
Your written response, as well as any questions or concerns about this letter or the inspection, should be sent via email to the FDA at CDER-OSI-Communications@fda.hhs.gov.
Sincerely,
{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
10/06/2026 10:05:58 AM