Tag: manufacturing

Pfizer Gets Green Light From the FDA on Epogen® Biosimilar

It has taken a long time, but Pfizer finally earned approval from the U.S. Food and Drug Administration (FDA) on the first biosimilar version of Epogen®. The drug, Retacrit® (epoetin alfa-epbx), had originally been submitted for approval in December 2014. Its much stalled road to approval is finally at an end.

After an initial rejection, the FDA’s Advisory Committee voted overwhelmingly (14–1) in May 2017 to give the product a green light. However, the FDA changed the traffic light to red, issued a second complete response letter in June 2017, citing issues with its manufacturing plant in McPherson, Kansas (a plant Pfizer inherited with its acquisition of Hospira).

Retacrit is approved for the treatment of anemia caused by chemotherapy or chronic kidney disease, for use in patients taking zidovudine for the treatment of HIV infection, and to reduce the need for red-cell blood transfusions before, during, or after surgery.

This is the 10th biosimilar approved by the FDA, and Pfizer is expected to shortly launch only the fourth biosimilar agent. Epogen’s patent has long expired, and it was one of the first biosimilars approved in Europe (in 2007). Retacrit has been marketed in the EU for over 10 years. It is one of four biosimilar epoetin products available overseas.

In other biosimilar news… Mylan’s earnings call on May 9 produced little clarity on the fate of its upcoming FDA decision on its pegfilgrastim biosimilar. Although CEO Heather Bresch believes that its product will represent one of its most important launches of the year, she could not shed any light on partner Biocon’s response to the FDA’s critical review of its manufacturing facility. The PDUFA date is June 4; a positive decision means that Mylan/Biocon will have beaten the competition to the market for this important biosimilar product.

Analyzing FDA Chief Gottlieb’s Remarks: One Challenge With no Easy Solution

Food and Drug Administration Commissioner Scott Gottlieb, MD, undoubtedly understands the threat to a successful biosimilar industry in the US, and his well-reported remarks emphasize some of the key issues. The policies that the FDA Commissioner wants to bring to bear on the multifaceted problem may be harder to implement. In this post, we examine one of those issues.

FDA Commissioner Scott GottliebIn the CNBC interview on Wednesday, he stated, “We’re taking a hard look at how we determine interchangeability so that we can make determinations that biosimilars can be used interchangeably with the brand of drugs.” Dr. Gottlieb correctly pointed out that the interchangeability question is complicated by “variants in lot-to-lot manufacturing of existing biologics and also a lot of variance in the products over time where there’s drift in the sort of formulation of the biologics that are currently on the market.” The variations that manufacturers of any biologics encounter create a “moving target” for not simply a manufacturer trying to prove biosimilarity but also interchangeability. He acknowledged that unexpected clinical effects of these variations have not yet been seen but the potential exists, which is why certain variations are subject to testing by the regulators to address the problem.

Yet, it is not practical to eliminate the lot-to-lot variation that has been seen for decades, sometimes incurred by plant changes or subtly different manufacturing techniques. Does this mean that biosimilar makers will have to test their agent against more samples of the originator biologic and in studies with more patients? For the purposes of proving interchangeability, the variation could undermine confidence in the outcome.

According to the FDA Commissioner, “We’re going to be putting out a set of policies to compel the branded drug makers who have biologics on the market to tighten up their manufacturing, to have less variance of their biologics that are currently on the market.” Preventing this variation in biologic manufacturing sounds like a costly (and possible futile) exercise. Let’s say for example, that one plant must be shut down for a time owing to maintenance; how does one prevent the manufacturer of a compound that demonstrates slightly different structural folding produced at another plant? Only an expert in biologic manufacturing techniques can answer this question.