Regulatory Focus™ > News Articles > Huge Batch of 483s to Pharmaceutical Compounders Show Sterility Concerns Endemic

Huge Batch of 483s to Pharmaceutical Compounders Show Sterility Concerns Endemic

Posted 01 April 2013 | By Alexander Gaffney, RAC

A crackdown on pharmaceutical compounders is growing ever wider, with the US Food and Drug Administration (FDA) adding another 15 inspection deficiency reports (Form 483s) to its website outlining a string of sterility problems increasingly seen as endemic throughout the industry.

In the wake of similar problems uncovered in late 2012-and a surge of interest from the media-FDA has started to post all Form 483 reports related to compounding pharmacies on its website. Those forms are used to list deficiencies found during inspections of a facility, and are often the precursor to formal warning letters that indicate pending regulatory actions.

Sterility Concerns

Those deficiencies are, more often than not, related to sterility concerns.

For example, a 483 sent to Central Admixture Pharmacy Services of Homewood, AL found that 18 orders of Cardioplegia had been distributed before sterility testing had been completed. Those tests failed, FDA alleged. Elsewhere in the facility, staff compounded products with their faces, necks and facial hair exposed to the products, raising FDA concerns about potential contamination from personnel.

At The Compounding Shop, a St. Petersburg, FL-based compounder, sterility concerns extended to Avastin (bevacizumab), which was observed to be manufactured in a process with numerous potential openings for contamination.

In a notable incident, FDA said that Portage Pharmacy of Portage, MI had not properly tested a compounded version of Hydroxyprogresterone Caproate. The drug, also known as Makena and 17P, has been at the center of a long-running battle between its manufacturer, K-V Pharmaceuticals, and FDA. In November 2011 FDA issued a statement indicating that it would allow pharmaceutical compounding pharmacies to make the drug, and issued a later statement indicating that it found no cause for concern that those pharmacies were manufacturing the products incorrectly. Portage was also found by FDA investigators to have not tested some of the lots for endotoxins or potency.

Birmingham, Al-based Medaus exhibited similar sterility concerns, which extended to the way in which products were stored. FDA claimed the products were stored at incorrect temperatures and without protection from ambient light. FDA said the company has explained to it that these products were routinely "placed on the counter daily between 8:00 am and 5:00 pm … to fill unit dose orders."

Another letter to PharmMEDium Services-the third yet sent to the company-regarding its Memphis, TN compounding facility, found similar violations regarding clothing worn by personnel, which did not cover facial hair or their face. Other employees were observed to be resting their hands on un-sanitized surfaces, which were then used in the compounding process without first re-sterilizing them.

Endemic Deficiencies

If there is a unifying theme across the deficiency letters, it is a breakdown in the ability of the facilities to ensure that both staff and the facility at large follow procedures for ensuring product sterility.

Every single one of the 15 Form 483s posted by FDA last week exhibited sterility concerns, as have all 14 other 483s posted by FDA previously, showing the widespread nature of the sterility failures across the industry and across geographic regions.

Those findings have repeatedly formed the basis of FDA's calls for additional authority to regulate pharmaceutical compounders, saying it lacks the resources and clear authority to do so. Most recently, FDA Commissioner Margaret Hamburg indicated that she was open to a proposal that would see the agency collect user fees from compounding pharmacies, presumably allowing it to bolster its inspection authority by hiring more staff. At present, most compounding pharmacies are overseen more closely by state regulatory officials than federal ones.

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