Quality control in academic cell therapy facilities: how much is too much?

Cellular therapy provides curative options for patients with viral infections, cancer and other diseases. The FDA and accrediting agencies have established specific laws, standards, and guidelines when manufacturing products for clinical use, including monitoring the environment according to FDA(21CFR Part 1271.195) and USP(1116). However, these documents are quite vague, especially for phase 1 and phase 2 clinical trials. Based on these documents we established our own environmental monitoring (EM) program. Here we tested whether our program adequately met the standards, whether there was any correlation between testing methods, and ultimately whether there was any correlation between our testing and positive sterility samples. Median particle counts in the ISO7/ISO8 were 7256(range: 423-54,131) and 43,697(range: 10,522-309,458), respectively, which are considerably lower than their designated classification. Median viable particles was 1. Touch plates ranged from 0-7 and 0-20/10 colonies/cm2, respectively. The majority of contaminants were skin flora. Adenosine Triphosphate (ATP) testing did not correlate with touch plates (R2=0.4), but were more representative in heavily contaminated areas. In the past year, ∼300 samples were submitted for sterility testing. One positive culture was reported and was traced to a punctured bag, so likely not a result of in-process contamination; no EM or clean facility can entirely prevent contamination when there is a breach in aseptic technique. Importantly, at the time of the incident all EM was below the alarm limit. Counting equipment, supplies, and staff, we calculated a cost of ∼$10,000/year for EM, or ∼$40/ft2. Moreover, we did not find a correlation between EM levels and positive sterility samples, nor did we find a correlation between ATP testing and touch plates. In conclusion, we found that our EM program is manageable on a small scale, though might prove challenging on a larger scale.