The U.S. Food and Drug Administration (USFDA) has released two important guidance documents addressing the risks of sepsis and Mycobacterium tuberculosis (Mtb) transmission in human cells, tissues, and cellular and tissue-based products (HCT/Ps). These recommendations are crucial for ensuring patient safety, donor eligibility, and screening procedures within the HCT/P industry, which includes organ transplants, blood-derived therapies, and regenerative medicine products.

Understanding the Risks: HCT/Ps and Infectious Diseases
HCT/Ps are biological products derived from human donors and are used in various medical procedures, including stem cell transplants, corneal grafts, heart valves, and reproductive tissues. Due to their biological nature, there is a risk of disease transmission from donors to recipients, making rigorous screening and testing essential.
Two of the most concerning infectious risks in HCT/Ps are:
Sepsis – A life-threatening response to infection that can be caused by bacterial, viral, or fungal agents present in donor tissues.
Mycobacterium tuberculosis (Mtb) – The bacteria responsible for tuberculosis, which can be transmitted through contaminated tissues, posing severe health risks to recipients.
To mitigate these risks, the FDA has provided detailed recommendations on donor screening, laboratory testing, and risk management practices.
Guidance 1: Reducing the Risk of Sepsis Transmission in HCT/Ps (Full Guidance)
Sepsis is a major public health concern when it comes to HCT/Ps. The FDA guidance focuses on identifying and preventing the transmission of disease agents associated with sepsis.
Key Recommendations:
1. Donor Screening and Risk Assessment
Donors should undergo a comprehensive medical history review to identify sepsis-related risk factors.
Physical assessments should look for signs of systemic infection.
Specific focus should be placed on hospitalized donors, as they are at higher risk of bloodstream infections.
2. Laboratory Testing for Sepsis-Related Pathogens
Testing should include bacterial cultures, blood tests, and pathogen screening in high-risk donors.
Results should be evaluated before tissue distribution to prevent contamination.
The FDA suggests sterility testing for HCT/Ps that are not terminally sterilized.
3. Preventive Measures in Tissue Processing
Aseptic handling and validated sterilization methods should be employed.
Tissues showing positive microbial contamination should not be used unless the pathogen is identified and deemed non-harmful.
Good Manufacturing Practices (GMPs) should be followed to reduce cross-contamination risks.
4. Post-Transplant Monitoring
Adverse event reporting should be conducted for any suspected sepsis transmission cases.
Healthcare providers must be alert to symptoms in recipients and report complications immediately.
Guidance 2: Reducing the Risk of Mycobacterium tuberculosis (Mtb) Transmission in HCT/Ps (Full Guidance)
Tuberculosis (TB) remains a global health concern, and transmission via HCT/Ps is a critical regulatory issue. The FDA’s recommendations provide a structured approach to identifying and preventing Mtb transmission in donor-derived tissues.
Key Recommendations:
1. Donor Risk Assessment for Tuberculosis
A detailed medical history should be collected, including past TB diagnoses, treatment history, and TB exposure risk.
Clinical symptoms of TB (chronic cough, weight loss, fever, night sweats) should be evaluated before donor approval.
2. TB-Specific Laboratory Testing
Tuberculin skin tests (TST) and Interferon-Gamma Release Assays (IGRA) should be used for screening high-risk donors.
Chest X-rays or CT scans should be considered if active TB is suspected.
Donors with active TB or untreated latent TB should not be considered for HCT/P donation.
3. Processing Controls for HCT/Ps
Heat sterilization and chemical disinfection should be considered for specific tissue types to eliminate Mtb contamination.
Molecular diagnostic methods should be used to detect Mtb DNA in tissues where TB risk is suspected.
4. Surveillance and Reporting of TB Cases Post-Transplant
Healthcare providers must report TB infections in HCT/P recipients to regulatory authorities.
Traceability systems should be in place to link infected recipients to specific donors.
Why This Matters: Strengthening HCT/P Safety Standards
The risk of infectious disease transmission via HCT/Ps is a critical concern for both regulators and healthcare providers. The USFDA’s proactive approach in issuing detailed screening, testing, and safety guidelines helps to:
✅ Enhance patient safety by reducing the chances of sepsis or TB infections post-transplant.✅ Improve donor screening protocols to identify high-risk individuals before donation.✅ Ensure tissue processing is held to high sterility standards, preventing contamination.✅ Strengthen pharmacovigilance by requiring continuous monitoring and reporting of infection cases.
By adhering to these updated guidelines, tissue banks, healthcare institutions, and regulatory bodies can collectively minimize risks while ensuring that life-saving transplants remain safe and effective.
To read the full guidelines:🔹 Sepsis Risk Mitigation in HCT/Ps🔹 Mtb Risk Mitigation in HCT/Ps
By following these recommendations, healthcare providers and tissue manufacturers can enhance patient safety and reduce infection risks in the growing field of regenerative medicine and cell therapy.
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