HCT/Ps: The 361 or 351 Question

Human cells, tissues, and cellular and tissue-based products are regulated under 21 CFR Part 1271. The question that decides everything about a product's path is whether it qualifies under section 361 of the Public Health Service Act, or whether it is a 351 product requiring a BLA.

The difference is total. A 361 HCT/P requires establishment registration, product listing, donor eligibility determination and current good tissue practice. A 351 product requires an IND, clinical trials, and a licence.

The four criteria

To be a 361 HCT/P, all four must hold:

Minimally manipulated. Processing does not alter the original relevant characteristics of the tissue relating to its utility for reconstruction, repair or replacement.

Intended for homologous use only. The product performs the same basic function in the recipient as it did in the donor.

Not combined with another article, with limited exceptions for water, crystalloids and sterilising or preservation agents.

Either has no systemic effect and does not depend on the metabolic activity of living cells, or if it does, is for autologous use, or allogeneic use in a first- or second-degree blood relative, or reproductive use.

Fail any one and the product is a drug, device or biologic, and the 361 route closes.

Where products fall out

Minimal manipulation is the criterion most often argued. Processing that alters the tissue's relevant characteristics takes you out, and enzymatic digestion that changes structural tissue into a cell suspension is the recurring example.

Homologous use is the one FDA has pressed hardest. Adipose tissue functions as cushioning and structural support in the donor; using it to treat a condition elsewhere is not homologous, whatever the clinical rationale. Much of the enforcement in this area turns on this criterion.

The enforcement record

This is not theoretical. Clinics marketing cell products under a 361 claim that FDA considers 351 products have received warning letters, and stem cell products appear repeatedly in current unapproved new drug enforcement. Searching the warning letter corpus for stem cell products returns a substantial set, most of it turning on homologous use.

If your product's 361 status rests on a reading of homologous use a reviewer might not share, that is a strategic question rather than a documentation one.