FDA Slaps Second Impax Plant with a Form 483
Impax received its second Form 483 in less than a week for a poor inspection of its U.S. manufacturing facility, igniting fresh doubts on the company’s plan to win approval of its Parkinson’s drug Rytary.
The brand and generics drugmaker disclosed the citation issued July 31 to its Hayward, Calif., plant following a June to July inspection that uncovered quality violations such as failing to review batch problems. That notice came just days after the FDA slapped the company’s Taiwan plant with a separate Form 483 for failing to reject contaminated batches and properly validating equipment.
The FDA observed, for example, that Impax’s October 2012 laboratory report on release testing of a lot of pyridostigmine bromide tablets was out of specification (OOS). But the facility didn’t address the ramifications of generating the OOS result and whether it impacted other manufacturing operations, the FDA said.
Impax also was dinged for several repeat observations, such as failing to test whether generic products are equivalent to their branded counterpart. Several products lacked an equivalency assessment, including orphenadrine citrate ER tablets, bupropion HCl ER tablets, oxybutynin HCl ER and rimantadine HCl tablets, the agency said.
Another repeat observation centered on poor data integrity, an area receiving heightened scrutiny from the FDA. The plant has two spectrophotometers that don’t have adequate controls to ensure analysts can’t rewrite or delete analytical data. The systems are used in testing raw materials, stability and release.
Investigators also found a walk-in stability chamber in disrepair. The agency found rust stains on the metallic floor underneath rubber floor mats, a sagging ceiling tile and corrosion on a drain pan, according to the Form 483 with seven observations. The chamber is used to store products for stability studies.
Impax said that it is working to address the FDA’s latest observations and will respond to the agency in roughly two weeks. Impax did not return a request for comment as of press time.
It remains unclear how this latest development will impact the drugmaker’s hopes to get approval of its NDA for Rytary (IPX066). The drug was rejected by the FDA last year due to continuing problems at the Hayward plant. While Impax resubmitted the NDA, continuous delays in getting regulatory approval led to GlaxoSmithKline’s exit from a development and marketing partnership surrounding Rytary.
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