Petition Asks FDA to Clarify Particulate Requirements in Injectable Drugs

May 22, 2015

The FDA should issue guidance officially adopting U.S. Pharmacopeia standards in its visual particle inspections of injectable drugs, law firm Hogan Lovells says in an April 13 citizen petition submitted to the agency on behalf of an unnamed drugmaker.

Even though the FDA has assured companies in the past that official sources such the USP suffice for documenting an acceptable particle quality limit, the agency is failing to follow the USP’s “essentially free” standard, the petition contends.

USP chapter 790 establishes a clear limit for visible particles: When 100 percent of the vials in a certain batch are inspected visually, no more than 0.65 percent should contain any visible particles.

However, according to the petition, a number of companies producing parenteral drugs in conformance with USP 790 continue to receive Form FDA 483 observations for particulate matter.

“As a result, they may be pressured to recall parenteral drug products even though the products are ‘essentially free’ of visible particulates and even though the risks of patient harm are assessed as low,” the petition says.

Company Responsibilities

As evidence of the FDA’s overly strict enforcement stance, the petition cites a significant jump in the number of Class I recalls for visible particulates in recent years — from just two such recalls in 2011 to 41 in 2014.

Issues with particulates have already forced major recalls by drugmakers this year, with Baxter, Sun Pharma, Hospira and Mylan all recalling injectables within the past several months.

Parenteral Drugs Association spokesman Walter Morris questioned Hogan Lovells’ petition, saying the FDA is obligated to accept all USP chapters below 1,000.

Drugmakers also are required to incorporate purity procedures into their manufacturing processes to ensure products contain the fewest possible particulates and are required to discuss their validation methods, as well as the level of patient risk associated with particulates, in their applications to the FDA, Morris says. Companies also must conduct their own visual inspections.

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