In August the US Food and Drug Administration (FDA) warned healthcare professionals about serious eye infections in Florida, US following intravitreal injections with repackaged Avastin (bevacizumab). Similar outbreaks occurred in other states, prompting researchers to investigate the events.
“Noncompliance with recognised standards and poor aseptic technique are the most likely causes of these outbreaks”, Florida-based researchers wrote in the American Journal of Ophthalmology. Avastin was used in the events as an off-label treatment of wet age-related macular degeneration.
Outbreaks of endophthalmitis have also occurred outside the US. The researchers note two possible causes of the events: sterile inflammation caused by improper storage or other manufacturing and distribution failings; and microbiological contamination.
“The presence of microbiological contaminants in the syringe can be explained only by improper procedures when compounding bevacizumab”, the researchers wrote. To cut the likelihood of these incidents the researchers say compounding pharmacies must follow US Pharmacopeia Chapter 797.
USP introduced 797 in 2004 to help compounding pharmacies ensure preparations are sterile. A revised version was published in 2008 to address concerns USP 797 placed too little emphasis on staff training and evaluation of aseptic technique.
FDA jurisdiction
Oversight of compounding pharmacies is a contentious issue. In the 1990s the FDA was given powers to identify drug products for which compounding posed a threat to efficacy or safety. By 2001 the US Supreme Court had ruled the powers were unconstitutional.
“The resulting dissolution of the FDA's Pharmacy Compounding Advisory Committee contributed to breaches in the enforcement of quality standards for compounding pharmacies”, the researchers wrote.
In 2010 the FDA filed an injunction against Franck’s Lab, a Florida-based compounder of veterinary products, five years after it sent a warning letter to the pharmacy. However, last year the court ruled against the FDA, finding that the Agency was overreaching its authority.
“What the FDA seeks to do here is reinterpret the [Federal Food, Drug, and Cosmetic Act] to allow it to eradicate the line between manufacturing and traditional compounding of animal medications”, Timothy Corrigan, the US District Judge ruling on the case, wrote.
K-V’s case
In November the FDA appealed the decision and continues to investigate compounding pharmacies. K-V Pharma prompted one FDA investigation when it presented data showing variations between its product, Makena (hydroxyprogesterone caproate injection), and formulations made by pharmacies.
“According to the analysis of this information provided by K-V, there is variability in the purity and potency of both the bulk APIs (active pharmaceutical ingredients) and compounded hydroxyprogesterone caproate products that were tested”, the FDA said.
The FDA began investigating the claim in November.