The QMN Weekly Bulletin

Three U.S. Manufacturers Land 483s Over Diverse Array of GMP Issues

June 17, 2016

Two domestic manufacturers and one in the territory of Puerto Rico have been called out by the FDA over inspection findings covering a diverse array of GMP concerns.

First up was specialty drugmaker Elite Laboratories, which received a 10-observation Form 483 over alleged issues uncovered at its Northvale, N.J. production facility. Three of the observations in the 483 relate to adverse events the company either neglected to follow up on or failed to report within statutory deadlines.

According to the 483, Elite failed to maintain oversight of six reported adverse events that the company received that were never investigated. Inspectors also determined that 11 of 24 adverse event reports involving serious or unexpected reactions were submitted to the FDA more than two weeks late. Between 2012 and 2015, nine of the company’s periodic adverse event reports were submitted late.

The inspectors also took issue with Elite’s investigations of batch discrepancies or specification standards, contending that two such inspections over the summer were not thorough enough.

Another area of concern was that testing of the blood pressure API isradipine and finished products failed to “ensure satisfactory conformance with specifications.” The document cites four such examples.

Elite apparently has neither properly established nor documented the accuracy, specificity and reproducibility of it testing methods, with the 483 noting that the in-house testing method was not validated.

The document also states there were unjustified deviations from written test procedures, as well as failure to follow procedures set by the company’s quality control unit.

In three instances, facility staff did not receive routine training for their roles in the production process, according to the FDA.

An Elite spokeswoman acknowledged receipt of the 483 and said the company has responded with “the appropriate corrective actions.”

Allergan Faulted on Recordkeeping

Actavis Laboratories received a two-observation Form 483 after the FDA unearthed potential issues with product storage and recordkeeping.

The document questioned the company’s handling of raw materials and finished products, claiming that Actavis had no temperature alarm system or humidity controls in its warehouses. On a related note, the document said that the company neglected to study the effects of shipping on product quality, despite regularly shipping finished products between various locations.

The allegations stem from a Jan. 14 inspection of Allergan’s Mariana West subsidiary in Sunrise, Fla.

Another complaint was that the firm neglected to conduct an investigation into a defective air handling unit. The agency says the unit was found defective in November 2014, and that when the inspector returned in January, the unit still had a notice on it left over from the 2014 inspection.

Actavis representatives did not reply to a request for comment.

AIAC Draws 6-Observation 483

The last company was Puerto Rico-based AIAC Pharma, which received a six-observation Form 483 over complaint management, cleaning records and apparent lapses in laboratory controls.

According to the 483, the firm did not include its investigation findings regarding the odor and taste of Propecia tablets — which the facility manufactures — in its complaint records. Specifically, there was no designated root cause listed in the manufacturing or packaging, the agency says.

AIAC also was hit for supposedly failing to extend investigations of unexplained discrepancies to other products potentially associated with the failure. For example, investigations of manufacturing deviations for Janumet XR tablets identified a root cause and a corrective and preventive action plan for broken tablets during production, but the company did not correlate the customer complaints with previous investigations.

The FDA further slammed the firm’s cleaning procedure used in the production area for Propecia. According to the 483, the procedure was not validated to ensure no drug traces were left on the equipment used in the process. The current cleaning procedure instead relies on visual observation, the agency says.

Moreover, the drugmaker failed to establish laboratory controls with appropriate test procedures to ensure the products conforms to standards of identity, strength, quality and purity.

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