Will Pharma And The FDA Act To Control Opioid Abuse?

By Ed Miseta, Chief Editor, Clinical Leader

Dr. Lynn Webster, president, American Academy of Pain Medicine and medical director, CRI Lifetree

The Centers for Disease Control and Prevention estimates that 16,000 Americans die each year from opioids. While some may be the result of suicide, many are accidental overdoses by both addicts and non-addicts. In an attempt to address the abuse of opioid drugs such as OxyContin, New York City recently announced it would begin restricting patients to a three-day supply of these painkillers. But Dr. Lynn Webster, president of the American Academy of Pain Medicine and medical director of specialized research organization CRI Lifetree, believes more needs to be done.

One of the problems the industry faces is identifying potential and existing abusers. Webster believes this is a complex question, and is likely a mix of individuals. “The people who end up abusing opioids can be people who are in pain and want to get more out of the medicine because what they are getting is not enough,” he says. “There are also patients who used it at one time and became addicted. However, it appears a majority of the people harmed by these drugs are non-medical users. This might be a person who received the drug after surgery and liked the effect, someone who was exposed to it at a party and became addicted, or perhaps a completely naïve user like a child who was given it by a friend. We really don’t have good data on who is dying from this, but it appears most deaths are appearing in people who did not have a prescription for the drug or were not using it for the treatment of pain.”

“We basically have two epidemics: an epidemic of pain and an epidemic of prescription drug abuse,” says Webster. “This presents a bit of a conundrum for everyone involved in the industry, including patients, providers, regulators, and legislators. On the one hand, opioids are the most powerful analgesic we have, and the only types of medication that will help some people manage pain. On the other hand we have a subset of the population, maybe 1 in 5 Americans, who are genetically vulnerable to the disease of addiction. For that reason it is vital for the industry to create better and safer medications.

Extended Release Creates Problems

One issue around which there is no debate is the adverse effects that can be derived from extended release formulations. Manufactured to provide extended (12 or 24-hour) relief to pain sufferers, these formulations are particularly risky and have contributed to a disproportionate amount of harm from the drug. Although the amount of active ingredient in extended release formulations is intended to relieve pain for a longer period of time, they can be manipulated so as to release the full effect into the system very quickly. The result can be satisfying to some abusers but can also be lethal.

One way to advance the safety of medications is to make it more difficult for users to manipulate them from extended release to immediate release. The industry can accomplish this by producing medications with abuse deterrent (tamper resistant) features. The most common method is drugs that are difficult to crush or pulverize. Webster notes great advances have already been made in this regard. On one news program, he was able to take an OxyContin pill produced using the old formulation (which is no longer sold), crush it between his thumb and forefinger, and create a fine powder that could be easily inhaled. The new OxyContin formulations are tamper resistant and cannot be easily pulverized. Users may be able to break one into chunks, but not easily into a powder.

“One company even has small, gel-like beads,” says Webster. “If you pulverize those beads, the technology retains the drug within the pulverized particles so the pain killer is still not released any faster. Another company has technology that will actually slow the release of the active ingredient when it is manipulated or tampered with.” While this will not prevent someone from ingesting a handful of pills, it will prevent them from injecting, snorting, or crushing them to get the full effect quickly.

Generics Pose A Risk

All of these advances, unfortunately, will be for not as generics begin to hit the market without the tamper resistant features. This is a problem that has Webster and many in the industry concerned. Historically, generic companies have only had to match the pharmakinetics of a drug. They are not required to match abuse deterrent features. If the problem we face is due to the ease at which extended release formulations can be manipulated, then allowing generics on the market at a lower price and without the tamper resistant features could potentially explode the problem.

“I would expect physicians and patients to move away from more expensive and safer products to less expensive generics,” says Webster. “This will eventually allow more of the drug to be available to those seeking it for non-medical purposes. That will not solve the prescription drug problem, it will make it worse. A generic of the original OxyContin formulation is already available in Canada, and will be easily obtained by users in the U.S. Anyone in Canada can bring product across the border, and an American going to Canada can also bring it back and pass it on to anyone they want.”

Three Solutions: FDA, Congress, And Pharma

Ultimately, the challenge will be for government and pharma to ensure abuse deterrents are the way of the future. For this to happen, generics are going to have to match up to the abuse deterrent properties of the brand name drugs. There are three ways for abuse deterrent features to make their way into generics. First, Congress can force the drug companies to make this happen. A bill that would have done just that, The Stop Tampering of Prescription Pills (STOPP) Act, stalled in 2012 without getting to the floor of the House.

Second, the FDA could act on its own to create incentives or requirements for drug companies, and do so without Congressional approval. In early 2013 the agency did issue guidance on abuse deterrent formulations for opioids that allow for brand products to use package inserts for marketing purposes. Historically, most of the work that has gone into developing safer products has not been recognized in the package inserts. “Drug makers have not been able to differentiate themselves from competing products that may have the same pharmakinetics but not the same abuse deterrents,” notes Webster. “But I think more needs to be done, and the industry now has the ability to work towards a goal. If we can add abuse deterrent features to brand products, then generics should have to reach the same bar, or they should not be allowed on the market.”

The third way is for pharma firms to take a leadership role and act on their own, rather than wait for regulators or legislators to tell them to do the right thing. Webster believes many of the companies developing generics have seen the writing on the wall and are developing tamper resistant properties before they file their generic application. He believes that if one firm does it, there will be an incentive for others to follow suit. This should be done for stimulants and other addictive pharmaceuticals as well as opioids.

“We need to keep in mind that what drives any industry is profit,” adds Webster. “But we need to ensure the incentive for profit does not outweigh the safety of the public. If one firm incurs the cost of producing a safer formulation, others need to do so as well to keep a level playing field. If everyone comes together in the best interest of the public, it is my hope that in five years only abuse deterrent formulations will be available.”