Get Ready; Get Set…. DEA Publishes Final Rule Rescheduling HCPs: Affected Registrants Must Swallow a 45-Day Compliance Window

August 24, 2014

By Karla L. Palmer

The U.S. Drug Enforcement Administration (“DEA”) published last Friday a Final Rule rescheduling hydrocodone combination products (“HCPs”) from Schedule III to Schedule II.  We posted about the proposed rescheduling here (NPRM published February 27, 2014).  There was little doubt that DEA would up-schedule HCP’s, especially in light of HHS’s recommendation to do so.  It is disappointing, however, that DEA did not heed the request of industry and provide for more time for the implementation of the heightened security and other requirements.  

The Final Rule comes on the heels of more than a decade of review of the rescheduling issue for HCPs by both the Department of Health and Human Services (“HHS”) and DEA.  Back in 2004, in response to a petition, DEA first submitted a request to HHS for a scientific and medical evaluation, and scheduling recommendation for HCPs pursuant to 21 U.S.C. § 811(b).  In 2008, HHS recommended that HCPs remain controlled in schedule III of the CSA.  In 2009, DEA requested HHS re-evaluate their data and provide another scientific and medical evaluation and scheduling recommendation based on additional data and analysis. 

The 2012 FDA Safety and Innovation Act (“FDASIA”) (summarized here) included a provision requiring review, including public meetings, on rescheduling of HCPs. That statutorily mandated review included the creation of an FDA advisory committee (Drug Safety and Risk Management Advisory Committee), which after two days of public meetings in 2013, and review of 768 comments submitted by patients, patient groups, advocacy groups, and professional societies, voted in favor of rescheduling.  After review of scientific and medical evidence, and other considerations mandated by FDASIA, HHS completed its required eight-factor analysis under 21 C.F.R. § 811(b) and recommended in late 2013 that HCPs be placed in Schedule II.  DEA published its notice of proposed rulemaking in late February 2014.

DEA received 573 comments on the proposed rule; it reports that 52% (or 298 comments) supported (or supported with qualification) rescheduling, and 41% (235 comments) opposed rescheduling (many opposition comments were from pharmacists).  Seven percent of the comments did not take a definitive position.  The lengthy preamble addresses comments received, and the 45-day period for implementation of necessary changes by registrants as a result of the up-scheduling.  Although DEA received comments seeking a longer implementation window, those comments did not deter DEA from sticking with what is perceived by many to be a woefully short transition period.  Specifically, in order to prevent “continued misuse, abuse and diversion,” DEA deems it “necessary to set an effective date for this scheduling action, including security and labeling requirements, with all reasonable haste.  After careful consideration of the risk to the U.S. public health and safety related to the diversion and abuse of HCPs, the DEA believes the 45-day effective date is reasonable.”  Final Rule at 61.  DEA also stated that it may not refuse to reschedule a drug or other substance based on alleged “economic impacts” of the rescheduling.  Furthermore, as to retail pharmacies, DEA noted that they are “not required by the CSA or DEA regulations to place schedule II controlled substances in a vault or safe.”  Specifically, in accordance with 21 CFR § 1301.75(b), pharmacies “may disperse schedule II controlled substances throughout their stock of noncontrolled substances in such a manner as to obstruct the theft or diversion of the controlled substances.”

DEA clarified that the Final Rule affects hydrocodone combination products, which are those substances described in 21 C.F.R. § 1308.13(e)(1)(iii) and (iv).  DEA noted that all other products containing hydrocodone are already controlled under Schedule II.  It specifically pointed out that Zohydro™ ER does not meet the cited definition; it is currently controlled under 21 C.F.R. § 1308.12(b)(1)(vi).  However, excluding Zohydro™, all “pharmaceuticals containing hydrocodone currently on the market in the United States are HCPs and are subject to this rulemaking,” including cough suppressants containing HCPs.   DEA noted that HCPs are the “most frequently prescribed opioid in the United States with nearly 137 million prescriptions” for HCPs dispensed in 2013.  Final Rule at 13.  

As we previously posted, rescheduling HCPs from Schedule III to Schedule II affects the entire drug supply chain – every handler of controlled substances.  (The effects of rescheduling are included in that post).  Rescheduling imposes significantly more stringent regulatory requirements on manufacturers, distributors, pharmacies, physicians, importers and exporters. 

The preamble addresses a multitude of issues raised by the rescheduling, including but not limited to the following:

1.   Authority to Prescribe HCPs as Schedule IIs

Commenters were concerned that prescribing authority differed in states, and now mid-level practitioners and others with no CII prescribing authority in certain states would not be able to prescribe HCPs.  DEA responded that it is outside its authority to decide who has prescribing authority within any particular state.

2.  Transmission Methods of HCP Prescriptions as Schedule IIs

Commenters were concerned about the inability for prescribers to transmit oral and faxed prescriptions for Schedule II HCPs. DEA responded that rescheduling does not hinder legitimate access to HCPs, and that contrary to the concerns of commenters, in the event of an emergency situation as defined in DEA regulations, a practitioner would be able to prescribe, and a pharmacy would be able to dispense, HCPs in accordance with 21 C.F.R. § 1306.11(d).  It noted however, in particular, that a practitioner may not delegate to a nurse, pharmacist, or anyone else, authority to make a medical determination whether to prescribe a particular controlled substances.  Final Rule at 49.  

3.  Quantity and Frequency of Refills

DEA noted that many commenters expressed concern about the limitation on refills on CII prescriptions, that this would required more frequent physician visits, and cause doctors to prescribe large quantities of HCPs per prescription.  DEA responded that, while courts have recognized that prescribing “inordinate” amounts of controlled medications may be a violation of the CSA, neither DEA nor the CSA generally imposes a quantitative minimum or maximum on the amount of medication.  Nevertheless, DEA recognizes that limitations on quantities by states or benefit providers exist, and that registrants must comply with such limitations.  Although the CSA prevents refills of CII prescriptions, DEA stated that practitioners may issue multiple prescriptions covering up to a 90-day period, and that DEA regulations do not require patients to be seen on a monthly basis.  DEA’s regulations, however, should not be construed “as mandating or encouraging” individual practitioners to issue multiple prescriptions or see their physicians only once every 90 days. 

4.   Patient Access

DEA received many comments voicing concerns related to access to HCPs, including fear of criminal prosecution, and impact on availability.  DEA stated that rescheduling should not hinder access to legitimate use of the medication, and that increased criminal sanctions for wrongful use, or use of the CSOS or Form 222 ordering process, should not result in limited availability.   DEA noted it takes approximately 1 hour to complete an order using a Form 222, and approximately 3 minutes to complete an order for CIIs using CSOS.

5.   Impact on Long-Term Care Facilities (“LTCFs”)

Although several comments addressed the detrimental effect that rescheduling will have on access to HCPs for patients in LTCFs, DEA responded that regulations already in place, such as permitting transmission of a prescription through the practitioner’s agent under 21 C.F.R. § 1306.11(f), and permission for partial fills under section 1306.13(b) already accommodate the unique needs of LTCFs.  DEA denied any request for a LTCF exemption based on lack of likelihood of diversion in LTCF settings, instead citing data demonstrating high incidents of diversion and abuse in such settings. 

6.   Impact on Manufacturers and Distributors
The most notable issue for the Final Rule for manufacturers and distributors is likely the 45-day implementation window for various HCP security and handling requirements.  For example, manufacturers and distributors must secure schedule II substances in a safe, steel cabinet or vault while schedule III substances may be stored in a less secure controlled substance cage or other enclosure.   DEA stated that, in accordance with the Administrative Procedure Act, most scheduling actions have a 30-day implementation period.  Final Rule at 55.  DEA deems the 45-day period to be a reasonable amount of time for registrants to comply with the requirements, and “was established upon a full consideration of the totality of the circumstances specific to HCPs” — discussed at pages 55- 62 of the Final Rule.

7.   Distribution of C-III Labeled HCPs Post Implementation of the Final Rule

DEA states that manufacturers are required to print on the labeling of each “commercial container of HCPs they distribute the designation of HCPs as “C-II”.  Final Rule at 63.  Furthermore, “it shall be unlawful for commercial containers of HCPs to be distributed without bearing the label properly identifying them ….as C-IIs,” and all labels must comply with the labeling requirements “on or before the effective date established in the final order for the transfer or addition.”  Thus, DEA is specifically requiring that commercial containers of HCPs distributed 45 days from date of publication be labeled as “C-II” and be packaged in accordance with 21C.F.R. part 1302. 

Further, DEA states that a “distribution” after the effective date of the Final Rule requires the use of a DEA Form 222 to transfer the substance.  A registrant may transfer upstream commercial containers of HCPs labeled as “C-III”, with utilization of a Form 222 in accordance with 21 C.F.R. § 1305.03.  DEA notes that, as discussed in the Economic Impact section of the Rule, manufacturers and distributors can make “minor adjustments” during the implementation period to meet the effective date requirement.  And, distributors have the option of returning stock labeled “C-III” to the manufacturer.  DEA declined to exempt manufacturers and distributors from physical security requirements for C-IIs given, among other things, their high potential for diversion and abuse, and recommends that registrants work closely with local DEA offices regarding submission of materials necessary for compliance with DEA security requirements.  Final Rule at 65.

DEA also clarified that regulations pertaining to labeling of commercial containers applies to distributions by distributors and manufacturers.  The DEA does “not regulate the labeling and packaging of commercial containers of controlled substances downstream of distributors.”  Final Rule at 64. 

Despite the fact that HCPs have been prescribed and handled as Schedule III drugs for decades, are the most prescribed narcotic in the United States, and there are significant differences in the regulatory requirements between Schedule II and Schedule III drugs, DEA’s unwillingness to provide more than a 45-day compliance window is both surprising, and disappointing, especially because fighting the prescription drug abuse problem requires a cooperative effort between the medical community, industry and the government.

We understand that this blogpost is just a short synopsis of the entire publication of the Final Rule.  We will publish additional posts in the coming days and weeks to address specific issues that arise as the registrants grapple with the effects – and the tight implementation timeframe – of DEA’s rescheduling decision.