Compounder Recalls, 483s and Warning Letters Continue in Wake of FDA Inspection Blitz

The wave of recalls of contaminated preparations and FDA-483s is continuing as FDA’s extensive inspection blitz of compounding pharmacies across the US hits the four-month mark.

As of the beginning of June, FDA had posted 48 FDA-483s, ten recall announcements and two warning letters stemming from the inspection crackdown that intensified in February in the wake of the meningitis crisis that began to surface last fall (see related stories below).  Most  of the 483s contain an extended list of significant flaws in aseptic practices and controls across the recipient’s operations, and most of the recalls have involved all of the firms’ recent sterile preparations.

FDA has now posted 483s issued through mid-April.  The most recent recall among the agency’s listings occurred at the end of May, and a second warning letter to a compounder inspected during the current crackdown was issued on May 15 and posted on June 4.  Notably,the firms receiving the warning letters were not among the ten that conducted recalls associated with the inspections.

Continuing in prominence in the FDA inspection findings were issues around sterility assurance, laboratory testing, failure investigations, validation, stability studies, complaint handling, and personnel/environmental monitoring.

In the keynote speech at the Food and Drug Law Institute (FDLI) conference in late April in Washington, D.C., FDA Commissioner Margaret Hamburg highlighted the inspection blitz as an important component in the current emphasis the agency is placing on drug quality  (IPQ “The News in Depth” April 26, 2013).

She reported that, as of that time, FDA had completed inspections of 56 sterile product compounding operations since the blitz began in February. Of these, 25 were conducted on a “for cause” basis in response to complaints, and another 31 were proactive inspections of compounders known to have produced sterile drugs in the past. [Editor’s Note: For an in-depth analysis of the results of the first 14 of these inspections, see IPQ “The News in Depth” March 10, 2013.]

Hamburg commented that “some of our observations during the inspections were truly startling,” providing evidence of out-of-control sterile practices at many of these compounding operations and their production of “shockingly unsafe drugs.” She noted that in some cases the agency’s authority to conduct the inspections was challenged.

The inspection cohort was identified using a risk-based model that included factors such as past serious adverse events or product quality reports when available, historical inspection data, referrals from state regulators or sometimes public information or media reports, Hamburg explained. Most of the operations inspected were not registered as manufacturers, and “pharmacies” are not required by current law to register with FDA or report adverse events, she noted.

[CLICK HERE for the complete story.em>. It includes an analysis of the GMP problems and the stability program shortcomings, in particular associated with the compounder recalls.  Nonsubscribers can purchase the story for $195 by contacting Karen Bertani (  For subscription/license information, click here.]

See related IPQ stories:

The Sterility Risks in Pharmacy Compounding Can Be Limited, Not Eliminated, Experts Stress at USP Forum

Pharmacy Compounding Will Remain Center Stage as FDA’s Focus Intensifies on Drug Quality, Hamburg Tells FDLI

FDA Inspection Blitz Reveals Weakness in Sterile Practices at Large Compounders

Letter from CDER’s Woodcock to PharMEDium Serves as Notice to Compounders and Hospitals on Need for Product/Patient Linkage

Iowa, Massachusetts, California and Virginia Intensify Compounding Pharmacy Crackdown

Mass. Closes More Compounders; Grand Jury Probes NECC; New Infection Types Reported; FDA Reaches out to States

FDA Inspection Findings of Sterile Practice Breeches at Ameridose Mirror Those at NECC

Congressional Hearings Expand Meningitis/NECC Probe; More Light Shed on Regulatory Gaps

IPQ November 2012 Special Report on the Crisis in Pharmacy Compounding and its Implications