Med-South Pharmacy, dba Partners In Care Orange Beach, AL, Sept. 28 (Nashville, TN).

FDA conducted an investigation Dec. 20-21, 2006 at the facilities of Med-South Pharmacy dba Partners In Care, which was initiated in response to reports of injuries relating to betamethasone acetate/betamethasone sodium phosphate multi-dose injectable drug product, which the pharmacy makes.

Additionally, on Feb. 21-23, and March 2, 2007, a follow-up inspection was conducted. During both instances, FDA documented serious violations.

The December 2006 investigation revealed the firm received at least 70 complaints associated with the use of betamethasone acetate/betamethasone sodium phos phate injectable suspension. The complaints included redness, large swollen areas, bruising at the injection site, rash, fever, and cellulitis, with some patients requiring intravenous antibiotics.

On Dec. 22, 2006, the firm initiated a voluntary recall of two lots. The company later revealed a new formulation had been implemented to "improve workflow", and an incorrect amount of benzalkonium chloride (BZK), used as a preservative, had been added to the product.

On March 2, FDA conducted a follow-up investigation and found there was a failure to establish and follow written procedures to prevent microbiological contamination of injectable drug products claiming to be sterile.

Specifically, the firm's manufacturing process had not been validated for the injectable drug products. In addition, the filters used to sterilize injectable drug products had not been tested for integrity; smoke studies had not been conducted in the critical areas; and, particulate matter was not being monitored. The autoclave cycles used to terminally sterilize injectable suspension drug products had not been validated and there was no verification of their effectiveness with biological indicators.

The company failed to test each batch of injectable drug products purporting to be sterile and/or pyrogen-free to determine conformance to such requirements. For example, the firm tests finished injectable drug products for sterility on a monthly basis only.

The inspection revealed there was a failure to ensure all components and injectable drug product containers and closures were, at all times, handled and stored in a manner to prevent contamination. Specifically, on Feb. 21 and 22, FDA documented empty, open, sterilized glass vials, which were exposed to environmental contamination.

The company did not test each batch of injectable drug product to determine conformance to final specifications, including identity and strength of each active ingredient, before release and distribution. The firm did not conduct product testing on all batches of its product prior to release.

The inspection revealed a failure to reject injectable drug product which failed to meet established standards or specifications and any other relevant quality control criteria. For instance, distributed methylprednisolone acetate which failed to meet the established assay specifications, was distributed without conducting any reprocessing or any other further action

There were no written procedures for production and process controls to assure the products had the identity, strength, quality, and purity they claimed to have and there was a failure to establish laboratory controls, including scientifically sound and appropriate specifications, standards, sampling plans and test procedures designed to assure the drug products conform to appropriate standards of identity, strength, quality and purity.

The company failed to establish a quality control unit which has the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging material, labeling, and drug products and the authority to review production records to assure no errors have occurred or, if errors have occurred, they have been fully investigated.

And, the letter also stated: "The company failed to verify the identity of each component of injectable drug product and its conformance with all appropriate written specifications for purity, strength, and quality."

The firm did not conduct and document a thorough investigation of any unexplained discrepancy or failure of a drug product to meet its specifications or to extend the investigation to other batches which may have been associated with the particular failure or discrepancy.

Specifically, the firm failed to conduct complete root cause investigations for three complaints involving injectable drug products, which could not be drawn into the syringe or discharged from the syringe.

There was a failure to assure all injectable drug products met applicable standards of identity, strength, quality, and purity at the time of use by establishing an expiration date determined by appropriate stability testing there was no written testing program designed to assess the stability of your injectable drug products.

The letter further said the company did not ensure all injectable drug products, set aside and held in unlabeled conditions, were sufficiently identified to preclude mislabeling and the company failed to prepare batch production and control records for each batch of drug product containing complete information, including documentation where each significant step in the manufacturing of the product was accomplished.

There were no written procedures for cleaning and maintenance of equipment used in the manufacture of the product. As well as there were no established written procedures describing in sufficient detail the receipt, identification, storage, handling, sampling, testing, and approval or rejection of components and drug product containers and closures.

The inspection also found there was a failure to routinely calibrate automatic, mechanical, or electronic equipment according to a written program designed to assure proper equipment performance. Specifically, the firm did not routinely calibrate scales, the autoclave, or sonicators used to manufacture the products. In addition, the firm did not have any written procedures addressing equipment calibration.

Further, FDA said: "The company failed to calibrate instruments at suitable intervals in accordance with an established written program. For example, the firm routinely did not calibrate pH meters. In addition, it did not have any written procedures addressing instrument calibration."

There were no written procedures describing in sufficient detail the control procedures employed for the issuance of labeling and the company failed to retain and store, under conditions consistent with product labeling, reserve samples which are representative of each lot or batch of finished injectable drug product.

The firm failed to maintain individual equipment logs documenting the date, time, product, and lot number of each batch of finished injectable drug product processed and it failed to ensure employees engaged in the proper training in CGMP compliance.

The letter went on to say: "The company did not reject components which failed to meet required specifications and it failed to calculate actual yields and percentages of theoretical yield at the conclusion of each appropriate phase of manufacturing." Val; QCIQS; 14239W

Med-South Pharmacy:

* No written procedures to prevent microbiological contamination

* Manufacturing process had not been validated for the injectable drug products

* Did not conduct and document a thorough investigation of failure of a drug product to meet its specifications

* No written procedures for cleaning and maintenance of equipment used