Los Angeles-based Chemica receives 4-item 483 for stability test chamber flaws.

No temperature mapping studies for stability test chambers resulted in a four-item 483 for Los Angeles-based Chemica.

The report, which was prepared by investigator Virgilio Pacio from the Irvine, CA, District Office, stated that Chemica manufactures thalidomide and benzphetamine hydrochloride for clients who use the active pharmaceutical ingredients (APIs) for developmental studies for future ANDA submissions. Both APIs in final product powder forms are bulk labeled for manufacturing, process, repacking and laboratory use only.

For the temperature mapping citation, inspection documents stated that stability chambers were used to store samples for stability studies. The ES2000 chamber, for example, contained stability samples for APIs, but during a walkthrough, Pacio noticed there was no inventory log for the ES2000 stability chamber. Also, a review of the qualification records showed an absence of temperature mapping studies.

"In addition," the EIR continued, "my review of the stability testing protocol for API thalidomide revealed that temperature mapping of the existing chambers has not yet been performed."

Valentekovich "indicated in the protocol and confirmed during the inspection that the test samples were placed between the control, monitor temperature and humidity sensors in the stability chambers, [thus] alleviating the concern of a non-uniform environment." The FDAer noted in response that absent the unloaded and loaded chamber studies, "there is no assurance of a uniform environment inside the stability chambers."

Pacio also cited the dionized water system used in API manufacturing operations, which was not periodically monitored for chemical or microbial quality.

When the inspector asked if these functions were being conducted, Valentekovich replied that the conductivity light was used and there was no microbial testing performed. "I responded that the conductivity light is not sufficient to monitor the chemical quality of the water system, as it is not quantitative," the EIR noted.

Regarding process validation, the EIR stated that it becomes a concern once the company has finalized the developmental formulation of the APIs and the batches will be utilized for ANDA submissions. "Process validation of the APIs should be completed once the APIs are utilized for commercial purposes."

The FDAer also commented regarding cleaning validation: "This should be completed for commercial purposes and should include a consideration for solvent residues in addition to drug residues. Analytical methods used should be validated and sensitive enough to detect the smallest possible drug or solvent residue from process equipment."

Chemica, Los Angles, 1/28-30/04, Doc. 109792M, $5.50 plus retrieval.

* The Checklist--Chemica

* Stability test chambers lack temperature mapping studies

* Dionized water system not monitored

By Joseph Pickett, Managing Editor