WARNING LETTER
Hemarus LLC
MARCS-CMS 688656 —
October 08, 2024
Delivery Method:
VIA UPS and Electronic Mail
Reference #:
CBER 25-688656
Product:
Biologics
Recipient:
Recipient Name
Padmasree Chigurupati
Recipient Title
Vice President of Quality and Regulatory Affairs
Hemarus LLC
4600 Military Trail, Suite 224
Jupiter
,
FL
33458-4813
United States
padma@hemarus.com
Issuing Office:
Center for Biologics Evaluation and Research (CBER)
United States
WARNING LETTER
October 08, 2024
CBER 25-688656
Dear Ms. Chigurupati:
During an inspection of your firm, Hemarus LLC, located at 1295 NW 40th Avenue, Suite 201, Lauderhill, Florida, conducted between April 15, 2024, and April 30, 2024, the United States Food and Drug Administration (FDA) documented significant deviations from the applicable Current Good Manufacturing Practice (CGMP) requirements for blood and blood components, set forth in Title 21, Code of Federal Regulations (21 CFR), Part 606 and additional biological products standards in 21 CFR Part 610-640, including those for human blood and blood products in 21 CFR Part 640. These deviations cause your blood and blood products to be adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. § 351(a)(2)(B).
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. The items of concern include, but are not limited to, the following:
1. Failure of the responsible physician to approve reinstatement of the donor into the plasmapheresis program when the donor’s protein composition values have returned to an acceptable level [21 CFR 640.65(b)(2)(i)].
For example, a serum protein electrophoresis test for a sample collected on March 22, 2024, from donor
(b)(6)
showed results with a total protein less than 6.0 grams per deciliter. Another sample collected from the donor on April 2, 2024, was within normal limits, and was reviewed and approved by physician substitute AP on April 8, 2024. However, there is no documentation that the responsible physician approved the reinstatement of this donor into the plasmapheresis program as required. Source Plasma was subsequently collected from donor
(b)(6)
on April 26, 2024.
2. Failure of the personnel responsible for the collection, processing, compatibility testing, storage or distribution of blood or blood components to have adequate training and experience, including professional training as necessary, or combination thereof, to assure competent performance of their assigned functions, and to ensure that the final product has the safety, purity, potency, identity and effectiveness it purports or is represented to possess [21 CFR 606.20(b)].
For example, since September 27, 2022, nine of
(b)(4)
employees approved as physician substitutes by your Medical Director failed to complete the
(b)(4)
(minimum) training program required by your Standard Operating Procedure, 03.05, “Physician Substitute Training Program”(Effective Date: 05-27-20).
3. Failure to follow written standard operating procedures for all steps in the collection, processing, storage, and distribution of blood and blood components for further manufacturing purposes [21 CFR 606.100(b)].
For example, on April 15, 2024, FDA investigators observed freshly collected units of Source Plasma being placed immediately inside cardboard boxes in freezer
(b)(4)
. This deviated from your Standard Operating Procedure, 06.15, “Plasma Product Storage” (Effective Date: 02-16-15), section 7.1, which states that “plasma must be frozen individually, in crates in the freezer, to allow air flow around unit until ‘core freezing temperature’ is achieved (determined thru [sic] validation of freezer).”
4. Failure to make and record a thorough investigation, including the conclusions and follow-up, of any unexplained discrepancy or the failure of a lot or unit to meet any of its specifications [21 CFR 606.100(c)].
For example, out of 26 Internal Investigation Reports (IIRs) reviewed during the inspection, 20 were not completed in accordance with Quality Assurance Procedures Manual, 10.25, “Investigation Tracking” (Effective Date:2-22-21). Issues noted include, but are not limited to, failure to open an investigation of an error; failure to identify a corrective/preventative action to be taken; failure to close-out the investigation; and failure of firm management and quality control unit to review the investigation.
5. Failure to maintain records concurrently with the performance of each significant step in the collection, processing, compatibility testing, storage and distribution of each unit of blood and blood components so that all steps can be clearly traced. All records shall be legible and indelible, and shall identify the person performing the work, include dates of the various entries, show test results as well as the interpretation of the results, show the expiration date assigned to specific products, and be as detailed as necessary to provide a complete history of the work performed [21 CFR606.160(a)(1)].
For example,
a. The following Donor Adverse Event (DAE) Reports were documented with notes and signatures from your firm’s responsible physician and were dated at times when the responsible physician was not at your facility:
i.On March 9, 2024, the responsible physician signed DAE # 03-24-002 and applied a temporary deferral due to a Hematoma/Bruise (Complicated). However, the Responsible Physician Visit Log indicates they visited on March 11, 2024.
ii. On February 20, 2024, the responsible physician signed DAE # 02-24-004 and applied a temporary deferral due to a Severe Citrate Reaction Event. However, the Responsible Physician Visit Log indicates they visited on February 19, 2024.
iii. On November 7, 2023, the responsible physician signed DAE # 11-23-002 and applied a temporary deferral due to a Hematoma/Bruise (Complicated). However, the Responsible Physician Visit Log indicates they visited on November 6, 2023.
b. Two versions of IIR # 2024-03-001 were found in your records pertaining to an overdraw which occurred on March 28, 2024. Multiple fields, including the Description, Immediate Action(s) Taken, Root Cause/Investigation, Impact on Donor Safety/Product Quality, and Corrective Action, contained information that was not consistent between the reports. Additionally, the reports do not identify the person that documented the information.
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 the law. You are responsible for reviewing your firm’s operations as a whole to ensure that you are in compliance with all applicable statutory and regulatory requirements.
We acknowledge receipt of your letter, dated May 21, 2024, responding to the FDA 483 and representing that you have taken various corrective actions to address the inspectional observations. Your response is inadequate to address the above-noted concerns. For example, in response to Observation 4, you have acknowledged that records were signed by the Medical Director on dates that they were not present at your facility; however, you have not explained how you will prevent this or your other, multiple record keeping deficiencies from occurring.
You should take prompt action to correct the violations described in this letter and prevent their recurrence. Failure to adequately address this matter may result in enforcement action without further notice, including, without limitation, seizure and/or injunction.
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 in your response to this letter. 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.
Send your electronic response to CBERDCMRecommendations@fda.hhs.gov. If you have questions regarding this letter, contact the Division of Case Management, CBER at (240) 402-9156.
Sincerely,
/S/
Melissa J. Mendoza
Director
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research
Content current as of:
10/15/2024
Regulated Product(s)
Biologics