23-item 483 for Allergy Labs citing aseptic processing, sanitation procedures, equipment cleaning.(Human drugs)

Allergy Laboratories, Oklahoma City, received a 23-item 483 for its sterile drug manufacturing facilities because its aseptic processing areas were deficient regarding the system for monitoring environmental conditions. Further, its written procedures for sanitation were not followed, according to FDA records. The report also documented numerous failures in the cleaning and maintenance of equipment.

The firm further received a 20-item 483 following an inspection of its allergenic extract manufacturing facilities (see below). Only the 483s were available as this publication went to press.

The sterile drugs audit, prepared by FDA investigators Margaret Armes and Lloyd Payne from the Dallas District Office, revealed that Allergy's environmental sampling of non-viable and viable particulates in two undisclosed production areas were not adequate to determine the air and surface qualities. Also, "environmental surface monitoring of viable particulates in the [undisclosed] Vial Wash Room and Sterile Gowning Room is performed [at incorrect intervals]."

The FDAers also found the firm to be deficient in its written procedures for cleaning and maintenance. For example, "the firm has not validated the procedures used to clean and sanitize the processing equipment and production areas," according to the 483. Also, a finalized validation report for the ephedrine sulfate injection USP drug product was not developed.

In addition, "written procedures for cleaning and maintenance failed to include parameters relevant to the operation."

Further, the report documented that the cleaning and sanitizing validation report for the phenylephrine hydrochloride injection USP and L-cysteine hydrochloride injection USP did not include suitability studies for the use of an undisclosed method for detecting phenyephrine hydrochloride and L-cysteine hydrocholoride following the cleaning process to ensure that no drug residues were present.

Also, procedures for the cleaning and maintenance of equipment were deficient regarding maintenance and cleaning schedules, including sanitizing schedules. For example, "the firm has not established a written procedure to prevent drug product contamination," the 483 stated.

Further, the bulk drug solution mixing tanks were not cleaned and sanitized prior to being placed into the Vial Wash Room from a non-classified storage area. Next, "procedures for the cleaning and maintenance of equipment are deficient regarding the protection of clean equipment from contamination prior to use." For example, the bulk drug solution mixing tanks were not covered or held in a manner that would prevent environmental contamination while being stored in a non-classified storage following cleaning.

The company also was cited because "equipment used in the manufacture, processing, packing or holding of drug products is not of appropriate design to facilitate operations for its intended use and cleaning and maintenance." Specifically, the water for injection system was designed or constructed of a material that could promote microbial contamination of the finished product. Further, there was clear, flexible plastic tubing used to connect an undisclosed part to the water for injection storage tank at one sample port. This resulted in a biofilm on the interior surface of the tubing.

In addition, sampling and testing plans for drug products were not described in written procedures, which included the method of sampling and number of units per batch to be tested. "Specifically, the firm does not have an SOP that addresses out-of-specification (OOS) investigations conducted by contract labs. There is no SOP that allow[s] the firm to re-test or re-sample a drug component if the initial tests from the contract lab indicate the product does not conform to specifications."

The next violation in the 483 noted that actual yield and percentages of theoretical yield were not determined at the conclusion of each appropriate phase of manufacturing the drug product. For example, the 483 stated, "the firm is not reconciling the use of the bulk solution during filling operations. The firm does not document the amount of bulk solution left in the carboy after filling operations have been completed."

Also, the company did not determine the theoretical amount of vials that were to be filled from the bulk solution that was manufactured, and it did not compare the theoretical vs. actual yields of filled vials to determine if an investigation was required.

Further, Allergy's written records of major equipment cleaning and use were not included in individual equipment logs. For example, "The firm does not document the use and cleaning of their mxing tanks in individual equipment logs. The firm does not have dedicated mixing tanks for the Ephedrine Sulfate Injection USP ..."

In the second inspection, investigators Julie Bringger and Jennifer Bridgewater from Center for Drugs also found that the firm lacked validation studies to support the current packaging and shipping practices. "Packaging and shipping conditions consist of placing the extracts in uninsulated cardboard boxes wrapped with a thin plastic strip, placing Styrofoam chips throughout the box and shipping the final container un-refrigerated to the customer," the report noted. There was no assurance by Allergy Labs that this shipping procedure maintained final product at the labeled temperature.

Further, the report noted the following violations relating to cleanroom practices and conditions:

* Personnel performing sterility testing were observed with exposed skin;

* A technician was seen sanitizing hands immediately before touching finger touch plates used for personnel monitoring,

* A technician was observed adjusting cleanroom clothing,

* There was no assurance that the results obtained from the surface monitoring of the laminar air-flow (LAF) hoods were valid;

* The base of the viable air-monitoring devices utilized in the sterile filling area were rusty and exhibited flaking paint;

* Personnel were observed wiping the surface of the LAF hood after filling final product and prior to performing surface monitoring.

In the materials system, the audit noted: "There are no incoming checks or specifications for filters used in sterile filtration and tubing used in the manufacturing of allergenic extracts."

Also, there were no incoming checks for petri dishes utilized in preparation of environmental-monitoring plates. The firm could not be reached for comment. Allergy Laboratories, Oklahoma City, 8/9-29/05, 10/3-7, 25/05, Doc. 109855M, $6 plus retrieval.

[check] The Checklist--Allergy Laboratories

[check] Aseptic processing flaws

[check] Written sanitation procedures not followed

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