WARNING LETTER
Palamur Biosciences Private Limited
MARCS-CMS 708579 —
December 11, 2025
Product:
Medical Devices
Recipient:
Recipient Name
S. Ramamoorthy, Ph.D.
Recipient Title
Chief Executive Officer (CEO)
Palamur Biosciences Private Limited
Boothpur Mandal
Mahabubnagar
509382
Telangana
India
ram.murthy@palamurbio.com
Issuing Office:
Center for Devices and Radiological Health
United States
WARNING LETTER
December 11, 2025
Dear Dr. Ramamoorthy:
This Warning Letter is to inform you of objectionable conditions observed during the United States Food and Drug Administration (FDA) inspection conducted at Palamur Biosciences Private Limited (PBS) from January 20, 2025, to January 27, 2025, by investigators from the FDA’s Office of Bioresearch Monitoring Inspectorate (OBMI) Foreign Inspection Cadre. This inspection was conducted to determine whether activities and procedures related to your participation in Good Laboratory Practice (GLP) nonclinical studies complied with applicable federal regulations. Specifically, FDA investigators focused on the list of studies below including, but not limited to, implantation, acute systemic toxicity, material mediated pyrogenicity (MMP), and guinea pig maximization tests conducted at your facility.
The list of studies below is not an all-inclusive list of studies impacted by the inspection or by the violations cited in this letter.
Study number
Test
231918
Implantation Study
24636
Implantation Study
231192
Acute Systemic Toxicity
231165
Acute Systemic Toxicity
231809
Acute Systemic Toxicity
231868
Acute Systemic Toxicity
24085
Acute Systemic Toxicity
24110
Acute Systemic Toxicity
24005
MMP
24084
MMP
24378
MMP
231866
Guinea Pig Maximization Test
231586
Guinea Pig Maximization Test
231191
Intracutaneous Reactivity
231196
In Vitro Cytotoxicity
These tests are used in nonclinical studies for the development of devices as that term is defined in section 201(h)(1) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h)(1), because they are intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or function of the body.
The inspection was conducted under a program designed to ensure that data and information contained in requests for Investigational Device Exemption, Premarket Approval applications, and Premarket Notification submissions are scientifically valid and accurate. Another objective of the program is to ensure that human subjects are protected from undue hazard or risk during the course of scientific investigations.
Our review of the inspection report prepared by the OBMI revealed serious violations of Title 21, Code of Federal Regulations (CFR) Part 58 - Good Laboratory Practice for Nonclinical Laboratory Studies, which concerns, among other things, requirements prescribed under section 520(g) of the Act, 21 U.S.C. § 360j(g). Compliance with Part 58 is intended to assure the quality and integrity of the safety data filed in a premarket submission. At the close of the inspection, the FDA investigators presented an inspectional observations Form FDA-483 for your review and discussed the observations listed on the form with you.
We received the initial response from your firm dated February 17, 2025, concerning our investigators’ observations noted on the Form FDA-483. We have since received follow-up responses to the initial response from your firm on the following dates:
April 13, 2025
May 12, 2025
July 8, 2025
August 12, 2025
September 16, 2025
This letter discusses your written responses to the noted investigators’ observations and requests prompt corrective action to address violations of 21 CFR Part 58. These violations include, but are not limited to, the following:
1. Failure of the study director to assure that all experimental data, including observations of unanticipated responses of the test system are accurately recorded and verified [21 CFR 58.33(b)].
The study director has overall responsibility for the technical conduct of the study, as well as for the interpretation, analysis, documentation and reporting of results, and represents the single point of study control. The study director’s responsibilities include ensuring that all experimental data are accurately recorded and verified. Examples of the study director’s failures to adhere to this requirement include, but are not limited to, the following:
a. For study 231918, the Animal/Bird Requisition and Issuance Record shows that the rabbits were 7-8 months old, but the breeding records do not include birth dates. Additionally, the animals were only given identification (R1 through R12) when they were enrolled in and throughout the study, and this identification cannot be traced back to the Animal Issue Record maintained by the Animal Breeding and Husbandry (ABH) department. The Animal Issue Record lists species/strain, sex, age range and body weight range for a group of rabbits issued for a particular study. However, there are no medical records associated with the individual rabbits and no way of verifying the accurate age of each animal. Because animal age can impact the analysis and interpretability of test results, it is important that the age of each animal in a study is accurately recorded and can be verified.
b. The raw study data for the acute systemic toxicity studies (231192, 231165, 231809, 231868, 24085, and 24110) and MMP studies (24005, 24084, and 24378) did not have the rate of intravenous administration of the bolus in each animal recorded. Additionally, the start and end time of intravenous injection are not recorded. Study plans for all acute systemic toxicity and MMP studies require that intravenous injections be administered consistent with the guidelines outlined in the International Organization for Standardization (ISO) 10993, Biological Evaluation of Medical Devices, and/or the United States Pharmacopeia (USP) Chapter 151, Biological Tests – Pyrogen Test, as applicable. The rates of intravenous injections were not recorded; therefore, it cannot be verified whether these tests were conducted according to the testing guidelines.
c. For study 24636, there were no records of physical examinations of Guinea Pigs 1 through 12 upon receipt of the animals from the vendor, upon release from quarantine, or before the surgical procedure. The health of the animals was not comprehensively examined and recorded at the start of the study and anesthesia status was not assessed before the surgical procedure. Therefore, it cannot be confirmed whether the animals were healthy or showing any abnormal clinical signs. Clinical observations are important to record for the reliability of the subsequent analysis of the responses of the animal to the test article, as well as for evaluating whether the animal needs any treatment or intervention.
As the principal point of study control, the study director did not ensure that all experimental data were accurately recorded and verified, which in turn yields questionable study results. Based on this failure, the FDA has concerns about the quality and integrity of data generated from the nonclinical laboratory studies conducted at your testing facility. Complete and accurate study data are necessary to allow FDA to fully assess the overall safety and risk of a device with an associated premarket submission. The unreliable data raises concerns about the quality and integrity of associated premarket submissions, which may put public health and safety at risk.
Your written responses are inadequate. The written responses provided revised standard operating procedures (SOPs), forms, and staff training records, but they do not include any planned preventive actions such as frequency (e.g., quarterly, annual) of audits to check for compliance or future training for new staff and/or new procedures. Additionally, while you provided a copy of the form, PRM/PBS/TOX/014, “Animal/Bird Requisition and Issuance Record” as evidence of the health status of the animals, the form lacks detailed documentation of physical examinations conducted by qualified personnel (e.g. veterinarian). Furthermore, while your responses propose corrections for the specific observations noted, you have not indicated whether any systematic reviews of your procedures will be conducted to identify and correct any systemic issues. Your explanation, when taken into consideration with the violations described above, which occurred in multiple studies, suggests systemic failures in study director oversight of nonclinical laboratory studies and brings into question the quality and integrity of safety data collected at your testing facility. Thus, your responses do not provide assurance that similar violations would not occur again.
2. Failure of the testing facility to have standard operating procedures in writing setting forth nonclinical laboratory study methods that management is satisfied are adequate to ensure the quality and integrity of the data generated in the course of a study. [21 CFR 58.81(a)].
SOPs should be adequate to ensure the quality and integrity of data generated in a study. However, not all SOPs appear to be adequate. Examples of your failures to adhere to this requirement include, but are not limited to, the following:
a. SOP/PBS/TOX/001, Recording of Body Weight and Procedure for Feed and Water Consumption, does not include procedures for calibration of the balance used for weighing animals. Section 5.1 of the SOP states that, “[t]he balance will be set and calibrated as specific to the balance in use.” However, there is no specific information as to who is responsible for calibration (e.g., study personnel assigned to each study) or when calibration should be performed (e.g., whether the calibration should be performed prior to body weight measurement or whether it should be performed at specific dates/intervals).
b. SOP/PBS/GEN/047, Sample and Reference Material Preparation for Biological Evaluation of Medical Devices, does not include detailed procedures for extraction depending on the test article (e.g., test articles indicated for prolonged or long-term tissue contact may require different extraction conditions than those with limited contact). Additionally, the SOP does not provide detailed instructions for monitoring of changes in the color of the test extract. Sample preparation is one of the crucial steps in biocompatibility testing of medical devices. Conditions of medical device extraction, such as extraction temperature, duration of extraction, and vehicle use can significantly impact the outcomes of a biocompatibility study.
c. SOP/PBS/PAT/012, Euthanasia of Laboratory Animals/Birds, does not contain sufficiently detailed procedures for administration of carbon dioxide (CO2) for inhalation euthanasia for rodents to fulfill the objective of rapid unconsciousness with minimal distress to the animals. For example, the SOP does not contain information about the settings of the flowmeter for the delivery of the CO2 gas or include specific procedures for using CO2 inhalation in rodents.
Failure of a testing facility to have adequate SOPs raises questions about the reliability and accuracy of the data and does not ensure the quality and integrity of data generated in a study. Inadequate SOPs yield inadequate protocols that introduce ambiguity and uncertainty as to how study requirements are to be followed, as well as inconsistent execution of studies and unreliable study results. Inadequate SOPs could result in study data with a high level of variability that challenges the ability to effectively interpret the study results associated with a device. This in turn adversely impacts a manufacturer’s and FDA’s ability to assess the overall safety and risk of the subject device prior to use in humans as a legally marketed device or for purposes of beginning clinical trials.
Your written responses are inadequate. The responses provided revised SOPs, forms, and staff training records, but they do not: (1) detail how your testing facility will ensure that applicable SOPs will be followed to ensure the quality and integrity of data generated in a study; and (2) address any planned preventive actions, such as frequency (e.g., quarterly, annual) of audits to check for compliance or future training for new staff and/or new procedures. Additionally, while your responses propose corrections for the specific observations noted, you have not indicated whether any systematic reviews of your procedures will be conducted to identify and correct any systemic issues, including ensuring that there are existing SOPs that cover all relevant functions, as well as ensuring that all SOPs are sufficiently detailed to allow personnel to correctly perform these functions. Thus, your written responses do not provide assurance that similar violations would not occur again.
3. Failure of the testing facility management to assure that personnel clearly understand the functions they are to perform [21 CFR 58.31(f)].
An example of the testing facility management’s failure to adhere to this requirement includes, but is not limited to, the following:
a. For Guinea Pig Maximization Test (GPMT) study 24838, the study personnel failed to identify and record adverse tissue responses to the injected adjuvant and clinical observations (e.g., difficulty breathing). SOP/PBS/TOX/008 indicates that after intradermal induction, skin reactions such as edema, erythema, and necrosis, along with other clinical signs will be recorded. However, the records that were reviewed did not indicate that clinical signs were recorded. In addition, there is no procedure that describes what clinical signs should be assessed to determine the health of the animal or how the technician would recognize skin reactions and distinguish between similar responses (e.g., between a “discrete” and “moderate” skin reaction). Furthermore, it was observed that study personnel training does not include species-specific in-life observations and when veterinarian oversight should be requested.
Failure of testing facility management to assure that all personnel clearly understand the functions they are to perform and are adequately qualified and trained creates a high level of variability that does not ensure the validity and quality of the data. Personnel that do not clearly understand the functions they are to perform cannot consistently perform tasks according to the SOPs. This can have a negative impact on a study and calls into question the quality and integrity of studies conducted at your testing facility.
Your written responses are inadequate. Your responses included revised SOPs, training records, and creating a new division for Ethology & Animal Welfare to focus on clinical sign observation, ethology, animal welfare training, and enrichment, in addition to appointing a technical consultant to assist with personnel training. However, it is not clear what oversight for the new head of Ethology and Animal Welfare will entail or what technical expertise will be provided by the technical consultant. Furthermore, your responses do not address planned preventive actions, such as frequency (e.g., quarterly, annual) of audits to check for compliance or future training for new staff and/or new procedures. Additionally, while your responses propose corrections for the specific observations noted, you have not indicated whether any systematic reviews of your training program will be conducted to identify and correct any gaps in personnel training. Furthermore, while you have provided training records containing quizzes that test personnel’s recollection of the training received, you have not described how personnel’s ability to perform the tasks in question will be assessed to ensure that the training achieves its intended goal. Thus, your written responses do not provide assurance that similar violations would not occur again.
4. Failure of the Quality Assurance Unit (QAU) to determine that no deviations from approved protocols or SOPs were made without proper authorization and documentation [21 CFR 58.35(b)(5)].
The QAU is responsible for determining that no deviations from approved protocols or SOPs were made without proper authorization and documentation. An example of the QAU’s failures to adhere to this requirement includes, but is not limited to, the following:
a. For study 231918, the study plan stated that the rabbits should have a supraglottic airway device inserted; however, the surgical records showed that an endotracheal tube was used for delivery of inhalant anesthesia. There is no record to indicate that this deviation was identified by the QAU, and there is no documentation to indicate that this deviation was made with proper authorization.
A reliable QAU is integral to the successful understanding and completion of any GLP study. Without appropriate QAU oversight, neither the sponsor nor FDA reviewers have assurance that the data in the final study report is accurate and valid. Failure to perform QAU functions can have a negative impact on a study and calls into question the quality and integrity of studies conducted at your testing facility.
Your written responses are inadequate. Your written responses include generating a record of an SOP deviation, performing a root cause analysis, and opening a corrective and preventative actions plan. However, your responses do not detail planned preventive actions, such as frequency (e.g., quarterly, annual) of audits to check for compliance of the QAU or future training for new staff and/or new procedures. Additionally, while your responses propose corrections for the specific observations noted, you have not indicated whether any systematic reviews of your QAU will be conducted to identify and correct any systemic issues.
In addition to the device studies described above, FDA investigators also observed that your facility performs studies intended to support the approval of new animal drugs. The overall conditions and practices at your facility, as exemplified above, may impact the validity and integrity of the data obtained to support new animal drug applications. For example, in study 19278, your records indicate you centrifuged the majority of blood samples before they were actually collected. In your response, you indicated you were unable to reconstruct what happened. This calls into question the quality and integrity of data generated from the nonclinical laboratory studies conducted at your testing facility. You should ensure that you consider animal drug studies as part of your corrective and preventive actions.
FDA investigators also observed that the exterior of the testing facility had significant accumulations of dirt, animal droppings, and potential pest harborage. Upon inspection of Block F, the HVAC equipment on the outside of the building was found to be surrounded by a large amount of dirt and debris that could attract and provide harborage for various pests and could potentially be caught up in the HVAC equipment, possibly causing failure. Such conditions may impact nonclinical studies conducted at your facility.
The violations described above are not intended to be an all-inclusive list of problems that may exist with your facility. It is your responsibility as a nonclinical laboratory to ensure compliance with the Act and applicable regulations.
Within 15 working days of receiving this letter, please provide documentation of the additional corrective and preventive actions that you have taken or will take to correct these violations and to prevent the recurrence of similar violations in current or future studies for which you are the testing facility. Any submitted corrective action plan should include projected completion dates for each action to be accomplished as well as a plan for monitoring the effectiveness of your corrective actions. In addition, please provide a complete list of all nonclinical laboratory studies of FDAregulated devices for the last five years, including the name of the study, the test article, the name of the study director and sponsor, and the current status of the study. Failure to respond to this letter and take appropriate corrective action could result in the FDA taking regulatory action without further notice to you. In addition, FDA could initiate disqualification proceedings against you in accordance with 21 CFR 58.202. If you believe that you have complied with the Act and FDA regulations, please include your reasoning and any supporting information for our consideration.
Your response should reference “CTS# EC250128/E001” and be sent via email to: Irfan.Khan@fda.hhs.gov.
A copy of this letter has been sent to FDA’s OBMI Foreign Inspection Cadre via email at FDAInternationalBIMO@fda.hhs.gov. Please send a copy of your response to that office.
If you have any questions, please contact Amrin Chowdhury by phone at (240) 402-8318 or email at Amrin.Chowdhury@fda.hhs.gov.
Sincerely yours,
/S/
Ouided Rouabhi, MS
Acting Director
DCEA1: Division of Clinical Policy and Quality
Office of Clinical Evidence & Analysis
Office of Product Evaluation and Quality
Center for Devices and Radiological Health
Content current as of:
12/30/2025
Regulated Product(s)
Medical Devices