Exela Pharma Sciences, LLC — FDA Warning Letter Findings

Your firm failed to thoroughly investigate any unexplained discrepancy or 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).

Your firm failed to ensure that each person engaged in the manufacture, processing, packing, or holding of a drug product has the education, training, and experience, or any combination thereof, to enable that person to perform his or her assigned functions (21 CFR 211.25(a)).

Laboratory records are deficient in that they do not include the initials and signature of the second person reviewing the record for accuracy (21 CFR 211.194(a)(8)).

Regarding your failing to have stability data to support a six-month expiration date for Sodium Chloride 0.9%, USP packaged in 500 mL polypropylene IV bags from a batch size of (b)(4) produced on the “ (b)(4) ” line in the (b)(4) building, your firm was not adhering to your SOP-QA-000064, “Stability Policy and Guidelines for Establishing Expiration Date or Beyond Use Date of 503B Product.” Section 6.1.5, of the SOP, states stability protocols will be established, and studies…

Your firm used (b)(4) media lot (b)(4) to release sterility testing of Sodium Acetate Injection (in vials). However, two tests of lot (b)(4) were invalidated and the third test was passed without scientific rationale. Your firm's investigation, QE-000487, states human performance was determined to be the root cause of the failed testing events. However, your firm did not document any specific human error identified when testing the (b)(4) media. Three other lots of test…

Your firm failed to establish acceptance criteria for the sampling and testing conducted by the quality control unit that are adequate to assure that batches of drug products meet each appropriate specification and appropriate statistical quality control criteria as a condition for their approval and release (21 CFR 211.165(d)). Outsourcing facilities must comply with CGMP requirements under section 501(a)(2)(B) of the FD&C Act. FDA’s regulations regarding CGMP requirements…

Regarding your firm’s visual inspection program, you committed to developing improvements to your existing visual inspection program, however, no information was provided of what you will do in the meantime before all the corrections have been made, evaluated, and revised, if needed, along with training. In addition, we have the following concerns with your planned corrections: You state that your defect rates will be based on (b)(4) Visual Inspection of Medicinal Products…

Your firm failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).

Your firm failed to establish written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).

You failed to perform contemporaneous two-person checks during the reading of environmental (b)(4) plates and subsequent data entry of the results in your (b)(4) software system. A single analyst reads environmental plate counts, takes pictures only of the positive counts, and then enters results in the (b)(4) software system. The Quality Control (QC) personnel later review and verify the results in the (b)(4) software system. There is no assurance the analyst read plate…

Your firm failed to conduct laboratory testing to determine whether each batch of drug product purporting to be sterile conforms to such requirements (21 CFR 211.167(a)).