Smart Surgical, Inc dba Burst Biologics — FDA Warning Letter Findings

Failure to determine as ineligible a donor who is identified as having a risk factor for, or clinical evidence of, any of the relevant communicable disease agents or diseases for which screening is required under 21 CFR 1271.75(a)(1) [21 CFR 1271.75(d)(1)]. FDA has identified Zika virus (ZIKV) as a relevant communicable disease agent or disease (RCDAD) under 21 CFR 1271.3(r)(2). Since ZIKV is a RCDAD, donors of umbilical cord, blood, placenta or other gestational tissues should be considered ineligible if certain risk factors are present. However, in May 2016, you began receiving umbilical cord blood units recovered from allogeneic donors in (b)(4) , an area considered at increased risk for ZIKV, and you failed to determine these donors as ineligible. These umbilical cord blood units were manufactured into BioBurst Fluid and BioBurst Rejuv and distributed throughout the United States. Although you have since developed new procedures that provide for assessing eligibility based on ZIKV, your prior deficiencies raise potentially significant safety concerns.

Failure to establish appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile, including procedures for validation of all aseptic and sterilization processes [21 CFR 211.113(b)]. Your firm failed to adequately validate the aseptic process used to manufacture BioBurst Fluid and BioBurst Rejuv (i.e., by performing media fill simulations) since manufacturing began in December 2015. Since then, your firm…

Failure to thoroughly investigate any unexplained discrepancy, or the failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed [21 CFR 211.192]. Specifically, since December 2015, your firm has had numerous sterility failures for batches of BioBurst Fluid and BioBurst Rejuv that you failed to investigate to determine the source of the contamination beyond identifying organisms (for example, a…

Failure to have an adequate system for monitoring environmental conditions in an aseptic processing area necessary to prevent contamination or mixups [21 CFR 211.42(c)(10)(iv)]. Your firm has not established an adequate system for environmental, including personnel, monitoring in the aseptic processing areas where BioBurst Fluid and BioBurst Rejuv are manufactured. For example: a. Your firm does not investigate personnel monitoring excursions that exceed your action limit…

Failure to withhold from use each lot of components, drug product containers, and closures until the lot has been sampled, tested, or examined, as appropriate, and released for use by the quality control unit [21 CFR 211.84(a)]. Specifically, you told our investigator that components utilized within UCB (umbilical cord blood) manufacturing are not sampled and tested prior to being used in production.