Shortages of some pharmaceutical products could be alleviated if the Drug Enforcement Administration (DEA) coordinated its efforts to control the supply of some drugs more closely with the US Food and Drug Administration (FDA), a new government report has found.
Background
In the US, drug products are primarily overseen by two federal agencies: FDA and DEA. The former regulates drugs in accordance with their efficacy, safety and quality. For example, FDA might approve an opioid painkiller based on clinical evidence indicating the drug alleviates pain, is safe for use in patients with pain and is manufactured to appropriate standards.
The latter agency, DEA, regulates drugs primarily in accordance with their risk of abuse and medical benefit. Under the Controlled Substances Act (CSA), DEA is able to “schedule” many drugs if it believes they pose a risk of abuse. Drugs are classified according to a sliding scale of medical benefits and potential harms. A schedule V drug, for example, has a recognized benefit and a relatively small risk of misuse or abuse. A schedule II drug, in contrast, may have a medical benefit, but a substantial risk of misuse or abuse.
Schedule I drugs have no recognized medical benefit as well as a risk of misuse or abuse. They are illegal under the CSA.
Control Quotas
One of the ways DEA works to keep scheduled drugs under control is by establishing quotas on their production. Under the CSA, DEA controls the production of schedule I and II drugs, including for research purposes.
These quotas—known as Aggregate Production Quotas (APQs), Bulk Manufacturing Quotas (BMQs) and Procurement Quotas (PQs)—determine the exact amount of each drug that is permitted to (legally) be produced in the US each year. For example, in 2015 DEA allowed 49,500,000 grams of codeine, a narcotic used in many cough suppressant products, to be manufactured.
However, DEA’s APQ system has come under criticism in recent years. In 2011 and 2012, many patients with attention deficit hyperactive disorder (ADHD) said they found it profoundly difficult to obtain FDA-approved ADHD treatments containing amphetamine salts, a DEA-controlled substance. In response to pressure from patients and legislators, DEA eventually increased its production quota on amphetamines intended for sale from 25.3 million grams per year to as much as 49 million grams per year in 2014.
GAO Report
But as detailed by Marcia Crosse, the Government Accountability Office’s (GAO) director of healthcare, in recent testimony before Congress, DEA’s trouble with amphetamines is hardly unique.
“In the last decade, shortages of drugs containing controlled substances have increased nationwide, preventing providers and patients from accessing medications that are essential for treatment,” Crosse wrote, citing a recent GAO report. As a result, a 2012 law known as The Food and Drug Administration Safety and Innovation Act (FDASIA) required FDA to coordinate with DEA to increase the production quotas of drugs known to be experiencing a shortage. Manufacturers can also directly request action by DEA in response to a drug shortage.
Unfortunately for DEA, Crosse said GAO found “significant weaknesses” in the way DEA managed its quota process for controlled substances. The agency frequently failed to meet regulatory deadlines for bulk manufacturing and procurement quotas, and on average took half a year to establish quotas in 2011 and 2012.
DEA also failed to respond to drug shortage adjustment requests within the 30 days statutorily required under FDASIA. GAO found DEA responded to just 21% of applicants within this time frame, and on average responded to applicants in “nearly 60 days.”
GAO said its interviews with drug manufacturers revealed that the delays had, in the opinion of the manufacturers, “caused or exacerbated shortages of some drugs containing Schedule II substances.” Manufacturers estimated that 17% of schedule II medicine shortages were caused by FDA between 2011 and 2013.
DEA said “inadequate staffing within its quota unit” was responsible for the delays.
GAO’s report called on DEA to improve its management of the quota system, including establishing performance metrics, protocols, policies and training materials for its staff.
DEA, FDA Coordination
Crosse also noted a “lack of effective coordination” between DEA and FDA when it came to drug shortages.
For example, DEA and FDA define the term “drug shortage” differently.
“FDA defines a drug shortage as a period of time when the demand or projected demand for the drug within the United States exceeds the supply of the drug.
As explained by GAO:
“In determining whether a shortage exists, FDA assesses if there is enough supply to meet demand by evaluating potential substitutes for the drug in shortage to determine whether drugs are clinically interchangeable.
In contrast, DEA officials told us that there is no shortage, from DEA’s perspective, as long as there is quota available to manufacture a given controlled substance, regardless of which particular manufacturers are producing the product and which strengths or formulations are available.”
GAO recommended the two agencies come to a consensus on the definition of drug shortage, calling it a critical barrier to effective coordination.
Another challenge is DEA’s lack of policies to coordinate actions with FDA. “A lack of such policies or procedures is not consistent with key practices for effective collaboration,” Crosse wrote. In addition, while FDASIA requires DEA to respond to manufacturer’s requests for quota increases within 30 days, no such deadline exists for DEA to respond to similar requests by made by FDA.
Crosse’s testimony appeared to be sympathetic to the difficulties FDA faced when trying to obtain information from DEA. Even GAO had a difficult time obtaining information on DEA’s quota system, she said.
“It is important to note that completion of our work was significantly delayed by DEA,” she wrote. “In particular, DEA refused to comply with our requests for information from and about [quota systems] until intervention by senior DOJ [Department of Justice] officials.”
It ultimately took GAO more than a year to obtain access to the quota information it sought, she added.
