Bone Matrix Graft Products Linked to Tuberculosis Risks, FDA Warns

The FDA is calling for more stringent screening of bone matrix tissue donors in light of repeated tuberculosis outbreaks among bone graft patients

Federal regulators are warning about a potential tuberculosis risk from bone matrix grafts, following a recent outbreak linked to products by Aziyo Biologics, which has resulted in at least two deaths.

The U.S. Food and Drug Administration (FDA) issued a bone matrix product safety communication on September 12, indicating it is working with the U.S. Centers for Disease Control and Prevention to investigate a recent Mycobacterium tuberculosis (Mtb) outbreak among bone graft matrix recipients.

In July, Aziyo Biologics issued a bone matrix recall impacting all of its viable products, after a single lot shipped to seven states was linked to cases of tuberculosis.

According to the CDC, at least 36 patients who underwent surgery using ViBone Modable or alloOss Plus with lot number #TDS222820 must be monitored for Mtb. The CDC indicates two deaths have already been linked to the products, but has not said how many other patients, if any, have fallen ill.

The products were sent to 13 different facilities in California, Louisiana, Michigan, New York, Oregon, Texas, and Virginia, between February 27, 2003, and June 20, 2023.

Bone Matrix Tuberculosis Problems

Tuberculosis is caused by the Mycobacterium tuberculosis bacteria, which spreads through the air when a person with TB in their lungs or throat coughs, sneezes, or talks. The infections are of such concern they need to be reported to the local or state health department tuberculosis program.

While most people infected with TB do not show symptoms, signs of an infection can include chest pain, breathing complications, chronic coughing, fatigue, chills, loss of appetite, shortness of breath, and swollen lymph nodes. Treatment of the infection often involves an extended course of antibiotics.

In the safety communication, the FDA notes that tuberculosis has been linked to the transplantation of bone products, heart valves, and dura matter allograft for decades. Collectively, these are known as human cell, tissue, and cellular and tissue-based products (HCT/P).

Most recently, in 2021, FiberCel Bone Matrix tissue products were linked to more than 100 tuberculosis illnesses. These were also manufactured by Aziyo Biologics, Inc.

FDA Calls for More Intensive Bone Matrix Donor Screening

In the case of the FiberCel bone matrix recall and Mtb outbreak, the contamination was traced back to a single donor.

The FDA has now issued new recommendations calling for increased screening measures to evaluate HCT/P donors for signs of infection. This includes ensuring those responsible for screening have appropriate medical training and are qualified to review clinical evidence for signs of TB infection or sepsis, which can be caused by tuberculosis.

In addition, the person responsible for screening donors must verify and document that screening criteria have been met and that the products are available for distribution. The agency also recommended that screeners maintain a knowledge of awareness about outbreaks and seek additional screening or retraining to learn to identify evidence of an increased risk of tuberculosis or sepsis.

“TB may be underdiagnosed due to the lack of clinical suspicion, inherent diagnostic difficulty, and/or attribution of a group of symptoms to alternate causes,” the FDA safety communication notes. “Although a donor with LTBI (lent tuberculosis infection) may be asymptomatic, a person with TB disease may have a number of symptoms or signs that can mimic or overlap with other medical conditions.”

Clinical evidence of a TB infection can include a prolonged cough lasting more than three weeks, coughing up blood or sputum, weakness or fatigue, unexplained weight loss, fever, night sweats, back pain, meningoencephalitis, headache, confusion, lymphadenopathy or lymphadenitis, or radiographic findings.

Potential donors should be screened for evidence that they have ever been suspected, or tested positive, for tuberculosis, was born in an area of the world where tuberculosis is endemic, has ever lived with someone with TB or currently has close contact with a person with TB, has ever worked in a long-term care setting, or has medical conditions, or is on medication, which can impair the immune system.

While all patients who received the recalled Aziyo bone matrix products have been notified, the FDA recommends any healthcare providers or patients who experience adverse events linked to bone matrix products submit a report to the FDA MedWatch adverse event reporting program.