Generic Injectable GMPs Again Prompt FDA Warning – APP Added to Non-compliance Watch List

Consumer complaint handling and failure investigation issues have placed another large generic injectable drug manufacturer, American Pharmaceutical Partners (APP), onto FDA’s GMP non-compliance watch list.

In a warning letter issued in late February, the agency highlighted the firm’s handling of a variety of consumer complaints for its sterile products – which included complaints of a vial containing an insect and other vials missing labels or containing particulate matter – and incomplete investigations of these incidents.

The warning letter also details FDA concerns with media fill failures and field alert reports (FARs) as well as the manufacture and interstate sale of unapproved prescription drugs.  As such, the APP letter continues a significant trend over the past five years of FDA compliance actions linking GMP and unapproved drug issues.  [Editor’s note: For an extended analysis of this linkage, see the IPQ May/June 2009 Special Report.]

The letter from FDA’s New York district focuses on the findings from a three-week inspection in mid-2011 at APP’s manufacturing facility in Grand Island, New York, which resulted in an 18-page 483 (link provided below).

APP, headquartered in Schaumburg, Illinois, is a wholly-owned subsidiary of Germany-based Fresenius Kabi.  The company purchased APP in mid-2008 for $3.7 billion to allow it to enter the U.S. market for generic injectables.

Particulate contamination problems have figured prominently in FDA warning letters to aseptic manufacturers both in the US and abroad – in particular, generic firms.  The resulting compliance remediation actions have, in some cases, contributed to or exacerbated shortages of the drugs being manufactured.

[The analysis of APP’s warning letter and its relationship to broader FDA enforcement themes continues for subscribers here.  Nonsubscribers can purchase the full story for $195 by contacting Karen Bertani (  For subscription/license information, click here].

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