Regulatory Focus™ > News Articles > FDA Updates Adverse Event Reporting Requirements for Tissue, Cellular Products

FDA Updates Adverse Event Reporting Requirements for Tissue, Cellular Products

Posted 19 February 2015 | By Alexander Gaffney, RAC

FDA Updates Adverse Event Reporting Requirements for Tissue, Cellular Products

When you hear the term "adverse reaction" in the life sciences industry, you're likely to immediately think about pharmaceutical or medical device products. But as a new guidance document from the US Food and Drug Administration (FDA) makes clear, cellular and tissue products are also subject to reporting requirements.


The new draft guidance document relates to human cells, tissues and cellular and tissue-based products—better known by their acronym, HCT/Ps. The products are somewhat unusual in that they are regulated under the Public Health Service Act (PHS, Section 361), and not the Federal Food, Drug and Cosmetic Act (FD&C Act), which is the backbone of most healthcare product regulation in the US.

It's also worth noting which products are covered under FDA's HCT/P regulations, and which are not. For example, whole organs aren't covered by the regulations, and aren't even overseen by FDA. Likewise, "minimally manipulated bone marrow," blood products and secretions (e.g. breast milk) aren't covered under the regulations.

That leaves just about every other tissue or cellular product covered, however. According to FDA regulations at 21 CFR 1271.3(d), the agency regulates most donated materials (aside from whole organs) from deceased donors, as well as cells, cord blood, and reproductive cells and tissues from living donors.

In other words, if it's "intended for implantation, transplantation, infusion, or transfer into a human recipient," and isn't on a short list of exempt products, FDA probably regulates it as an HCT/P.

Guidance Details

FDA's guidance document is written, it said, with HCT/P establishments (i.e. "manufacturers") in mind.

"All non-reproductive 361 HCT/Ps are subject to the adverse reaction reporting requirements under §1271.350(a)," the agency explains in the guidance. For example, donated cartilage, ligaments, skin, tendons, heart valves and fascia all fall under the scope of FDA's reporting guidelines.

So which events need to be reported to FDA under its reporting requirements? FDA says any adverse reaction involving a "communicable disease" must be reported, as should any fatal or life-threatening event, or an event which caused "permanent impairment" or one which "necessitates medical or surgical intervention, including hospitalization."

The establishment which makes the product available for distribution must report the event, FDA said.

Reports must be made within 15 days of the establishment becoming aware of the event, and should include information regarding the symptoms and outcome of the reaction, the recipient's medical history, relevant test results and a history of the patient's other transfusions/infusions/implants/transfers "that may have been a source for communicable disease transmission." Form 3500A should be used.

The guidance also includes extensive information regarding the information each manufacturer should review prior to submitting an adverse event report, including processing information, environmental information (e.g. storage conditions), tracking information related to other products, and whether the product labeling is still appropriate.

The draft guidance is intended to supersede a similar guidance issued in 2005, FDA said in an accompanying Federal Register announcement.


Investigating and Reporting Adverse Reactions Related to Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) Regulated Solely under Section 361 of the Public Health Service Act and 21 CFR Part 1271 (FR)


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