WL Altaire Pharmaceuticals, Inc. MARCH 12, 2020
1. Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).
Your firm manufactures sterile ophthalmic drug products which are subject to approved FDA applications for human and veterinary drug products. Additionally, your firm manufactures sterile ophthalmic over-the-counter (OTC) and homeopathic drug products.
Our inspection revealed serious data integrity breaches and other serious violations relating to environmental and personnel monitoring.
We found that plates taken from ISO 5 areas exceeded action limits, but your firm failed to initiate investigations.
Furthermore, laboratory technicians falsified this data which is critical to maintaining an ongoing state of control in your aseptic processing facility. For instance, an environmental monitoring plate was recorded by your technician as “0” on your viable surface monitoring report form. The discarded plate was retrieved that same day and observed to contain colonies too numerous to count.
In addition, although you failed to conduct “post activity” personnel monitoring for up to a year, your technicians repeatedly recorded results of “0” on the personnel (b)(4) report form. Personnel monitoring samples are critical because they indicate whether or not personnel in the aseptic processing environment are adversely affecting quality.
Due to this lack of authentic data relating to the microbial control of personnel who perform aseptic processing operations, you lacked information that is basic to determining aseptic processing control. For up to a year, you lacked the ability to identify microbial contamination risks posed by personnel.
Your failure to reliably record data, the systemic flaws that led to these fundamental data integrity breaches, and your lack of sufficient investigations into both, raises questions regarding integrity of data throughout your operation...
2. Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).
You falsified laboratory data used to make batch release decisions for sterile ophthalmic drug products. In addition, you did not perform a required (b)(4) test to determine whether (b)(4) contained viable microorganisms. Your firm released these products to the market despite the lack of accurate and reliable analyses for products purporting to be sterile.
Specifically, your laboratory technicians recorded no growth (“NG”) for (b)(4) of sterility test media that were observed during the inspection to be turbid. Although (b)(4) were found to be turbid, you did not deem the product to be non-sterile or perform the additional (b)(4) step that is critical if a (b)(4) inherent turbidity issue is suspected. Regarding the latter, if a laboratory suspects that the turbidity could be of a non-microbial nature, (b)(4) is performed to ensure that such inherent turbidity is not masking microbial growth. Notably, your firm’s procedure (b)(4).
Your firm believes deficient laboratory practices relating to preparation of both of the sterility test media led to the turbid appearance of sterility test canisters. You stated that at the time of the inspection “(b)(4) was not prepared to be particulate free” and that the (b)(4) sometimes appeared with tiny black particulates.” You “determined that the source of such was overheating the glassware which burned some of the medium at the bottom of the vessels.” Your response stated that you will formalize a procedure for “when and how to perform (b)(4).”
We also note that you committed to have all products currently within expiry sterility tested by outside laboratories. Note that finished product sterility testing has limitations: it does not, on its own, establish the sterility of all units in a given batch because contamination is not normally uniformly distributed. Examples of other essential information to be evaluated along with the sterility test include data on the capability of the process to produce a sterile product, as well as data on the facility and process conditions associated with a given cycle of batch production.
In addition, the method suitability data you submitted for your contract lab, (b)(4), was insufficient. It is your responsibility to ensure contract laboratories are qualified, including but not limited to their use of methods and equipment that are validated and suitable for the analysis of your drug products...
