Warning Letter for an American Manufacturer of Blood Products

The United States Food and Drug Administration (FDA) inspected Hemarus LLC's facility in Lauderhill, Florida. During the inspection, the FDA identified numerous significant deviations from Current Good Manufacturing Practices (cGMP) for blood and blood components, as outlined in 21 CFR Part 606 and other regulatory standards for biological products.

Key Deviations Identified

Failure to Obtain Responsible Physician Approval for Donor Reinstatement: The company failed to ensure that a responsible physician approved the reinstatement of a donor into the plasmapheresis program after the donor's protein composition returned to normal levels. A donor with low protein levels was later found to have normal protein levels. Although this result was reviewed by a physician substitute there was no documentation of approval from the responsible physician for the donor's reinstatement. Plasma was subsequently collected from this donor in violation of the regulation.

Inadequate Staff Training: Hemarus LLC did not ensure that personnel responsible for blood collection, processing, and related activities had adequate training. Nine employees approved as physician substitutes by the Medical Director had not completed the required training program. This violated the company’s own Standard Operating Procedure (SOP) for physician substitute training. This lack of proper training puts the safety, purity, and quality of the blood products at risk.

Failure to Follow Standard Operating Procedures (SOPs): The firm did not adhere to its SOPs for the proper collection and storage of blood products, specifically in relation to plasma freezing procedures. The FDA investigators observed plasma being placed directly into cardboard boxes in a freezer, contrary to their SOP, which requires plasma to be frozen individually in crates to ensure proper airflow and freezing. This deviation from established SOPs increases the risk of compromised product quality.

Inadequate Investigation and Documentation of Discrepancies: The company failed to conduct thorough investigations into discrepancies and failed to document conclusions and corrective actions. The FDA reviewed 26 Internal Investigation Reports (IIRs) during the inspection and found that 20 were not completed in accordance with the company's Quality Assurance Procedures Manual. Problems included a failure to open investigations for errors, incomplete documentation of corrective actions, failure to close investigations, and inadequate review by firm management and the quality control unit. This lack of thorough investigation and corrective actions poses a risk to the safety and efficacy of the blood products.

Discrepancies in Donor Adverse Event (DAE) Reports: In several instances, the responsible physician signed DAE reports on dates when they were not present at the facility. For example, a DAE report for a hematoma on March 9, 2024, was signed by the physician, but the Responsible Physician Visit Log showed the physician was only present on March 11, 2024. Similar discrepancies were found in other cases.

Inconsistent Internal Investigation Reports (IIRs): Two different versions of IIR #2024-03-001 related to an overdraw incident on March 28, 2024, were found in the firm's records. These versions contained conflicting information about critical elements such as root cause analysis, corrective actions, and impact on donor safety. Additionally, the identity of the person documenting these reports was not recorded, further complicating traceability and accountability.

These and many other defects were found during the inspection.

In summary, the inspection revealed critical issues related to inadequate physician oversight, insufficient staff training, failure to follow SOPs, poor investigation procedures, and serious record-keeping lapses. Hemarus LLC must take immediate steps to correct these issues to avoid potential enforcement actions that could impact the firm’s ability to operate. You can read the full FDA Warning Letter on the website.