Laird Harrison

April 29, 2015

SAN DIEGO — New federal regulations could limit the supply of ophthalmic drugs, such as macular degeneration formulations of bevacizumab (Avastin, Genentech), report pharmacists.

"I think this is going to kill Avastin," said Charles Leiter, PharmD, from Leiter Compounding Pharmacy in San Jose, California.

Dr Leiter discussed the regulations during a workshop on the Drug Quality and Security Act here at the American Society of Cataract and Refractive Surgery 2015 Symposium.

The act was signed into law in 2013 after a 2012 outbreak of fungal meningitis killed 65 people. Investigators traced the infections to injectable drugs contaminated at the New England Compounding Center in Framingham, Massachusetts. Two pharmacists from the center have been charged with second-degree murder in the deaths of 25 people, as reported by Medscape Medical News.

Historically, states have taken the lead in regulating compounding pharmacies. But more compounders have been distributing drugs across state lines, and the New England case led to calls for federal oversight.

New Compounding Facilities

The Drug Quality and Security Act was developed in response to that need. The act created a class of "outsourcing" facilities that submit to federal oversight. In return, they can compound unlimited amounts of drugs on a list approved by the US Food and Drug Administration (FDA). And, unlike other compounding pharmacies, they don't need a physician's prescription to sell the drugs.

Fifty-one pharmacies have already registered as outsourcing facilities, but the FDA has not clarified the standards under which they can manufacture drugs, said Mark Baum, from Imprimis Pharmaceuticals in San Diego.

We have built a beautiful state-of-the-art facility in New Jersey, but we have no idea what we can make.

This is becoming an urgent problem for outsourcing facilities. "We have built a beautiful state-of-the-art facility in New Jersey," he said, "but we have no idea what we can make."

In fact, aspects of the proposed FDA regulations could make some drugs impossible to produce, Dr Leiter said.

For example, these regulations would impose a beyond-use date for bevacizumab and other biologics of only 5 days, but it takes 14 days just to test the sterility of these drugs, he explained.

The cost of complying with the new regulations will drive many small pharmacies out of business or force them to consolidate, he predicted.

This will make it hard for doctors to obtain small quantities of drugs for individual patients, or to get drugs on an emergent basis or to use for charitable work, said Baum.

The regulations could mean that compounded ophthalmic drugs besides bevacizumab — such as ophthalmic mitomycin, a phenylephrine and ketorolac injection, and a triamcinolone acetonide plus moxifloxacin hydrochloride injection — will become much more expensive or even unavailable, he explained.

"The bottom line is that drugs are going to get harder or impossible to get," said Dr Leiter.

Safety First

The goal of the FDA is to make safe and effective drugs available as quickly as possible, said Wiley Chambers, MD, from the division of transplant and ophthalmology products at the FDA.

The agency has special programs to accelerate the approval of drugs that treat serious conditions or conditions for which there is no current treatment. Two drugs for diabetic macular degeneration — ranibizumab and aflibercept — were granted accelerated approval through the breakthrough therapy designation, he reported.

There are consequences to marketing unapproved products.

But the FDA is also charged with maintaining the safety of drugs and devices. "There are consequences to marketing unapproved products," Dr Chambers said.

For example, in 2005, Custom RX Compounding Pharmacy in Richfield, Minnesota, recalled trypan blue 0.06% ophthalmic solution because of possible contamination with Pseudomonas aeruginosa. And in 2006, the FDA requested that Cytosol Laboratories in Lenoir, North Carolina, recall its balanced salt solution, which is used for irrigation in cataract surgery, because of "elevated and dangerous levels of endotoxin."

Anyone who wants to sell a drug should apply for approval, he stressed.

"Most of the time when someone asks me why a particular product has never been approved, my answer is that no one ever submitted the application," he said. "We can't approve something that hasn't been submitted."

Dr Leiter is chief executive officer of Leiter Compounding Pharmacy. Mr Baum is chief executive officer of Imprimis Pharmaceuticals. Dr Chambers has disclosed no relevant financial relationships.

American Society of Cataract and Refractive Surgery (ASCRS) 2015 Symposium. Presented April 19, 2015.


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