An epidemic that has been brewing for years now is coming into clearer focus: the use of fentanyl to lace illicit opioid-based drugs with higher potency, resulting in thousands of deaths nationally. The topic made Page 1 news on the Wall St. Journal yesterday (Oct. 6) with a somewhat innocuous headline, “The pill makers next door,” but the details in that story should be of concern to many drugmakers, including generic oral solids.
The current fentanyl/opioid epidemic has seen deaths from overdoses nearly doubling from 2013 to 2014 with some 5,500 deaths in that year according to CDC statistics. Academic papers published earlier this year cautioned emergency room physicians to test for the presence of fentanyl when overdose patients arrive; the proper diagnosis can help recovery.
DEA and other federal agencies have been tracking the growth of opioid drugs mixed with fentanyl for a couple years; a recently published Intelligence Brief notes that much of the fentanyl comes from labs in China, especially after a lab in Mexico was shut down in 2006. At that time, most of the fentanyl was being used to increase the potency of heroin; now, it’s going into pills, and some of the pills are formed to simulate the trade dress of legitimately produced opioid medications. The insidiousness of this is two-fold: street prices for pills that look like prescription products can sell for a premium (in fact, heroin and other drugs have long been “branded” in various ways); and as the US drug supply and distribution system gets better at managing the use of legitimate opioid-based medicines, the value of the counterfeited product goes up. (Just this week, DEA issued its so-called Aggregate Production Quota for 2017, the volume of opiate APIs used to produce prescription products and research purposes, by 25% or more in some cases, based on the declining rate of prescribing going on now.)
The other aspect of concern is that it is ridiculously easy to counterfeit currently manufactured opiates. The generic products have some simple cut lines or letter-number combinations (see photo); these pills are being counterfeited by hand using simple pill presses that cost around $1000. (DEA actually tries to control the import of pill presses, but they can get through Customs by being delivered as parts claimed to be other types of equipment.) The “next door” pill maker highlighted in the WSJ article was a husband-and-wife couple operating out of a two-bedroom San Francisco apartment. “The seizures of fentanyl-laced pills and clandestine pill press operations all across North America indicate that this is becoming a trend, not a series of isolated incidents,” warns DEA.
Fentanyl is 50 times as potent as heroin; if there are more than two milligrams of fentanyl in an opioid pill, it can be fatal. DEA says that a kilo of fentanyl can be purchased for prices ranging from $1,700 to $3,500; at 1 mg per pill, that kilo translates into $10-20 million in profit at street prices of $10-20 per pill.
Mallinckrodt, like most other makers of opioid-based medications, has been fighting energetically to prevent abuse of its legally prescribed prescription products; now it is dealing with counterfeits displaying the same “M367” trade dress on its pills. “We have been working with the US DEA concerning their investigation into the California incidents. More broadly, Mallinckrodt has supported and worked over multiple years with law enforcement at all levels concerning counterfeit versions of products the company manufactures,” the company told Pharmaceutical Commerce after the WSJ article appeared. For conventional abuse (if such a concept is even meaningful), the company’s actions have included “opioid educational efforts, monitoring for suspicious orders of controlled substances, drug deactivation and disposal programs, and research into abuse-deterrent technologies;” it also supports the establishment of prescription-drug monitoring programs (PDMPs), which are state-level actions to prevent doctor-shopping to fill multiple prescriptions for opioid products. (Ironically, Missouri, the home state of Mallinckrodt, is the only one lacking such a program.)
DEA’s Intelligence Brief notes that there are other counterfeiting activities going on; one cited is counterfeit Xanax (benzodiazepine). This indicates that drug traffickers “are also willing to utilize fentanyls in other non-opiate drugs with exploitable user populations,” DEA concludes.
There are criminal penalties for both drug counterfeiting and for illegal drug distribution; generally speaking, the penalties for the latter are more severe than the former. So it might make some sense that the homebrew counterfeiter is getting more attention from DEA than from FDA. But the enormous profits available to fentanyl-containing counterfeiting, combined with the lethality of the practice, might change law enforcement’s thinking. Bills have been introduced to Congress in multiple recent years to increase the penalties of counterfeiting to include life in prison or other penalties, but have not passed to date.