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Federal Register / Vol. 86, No. 87 / Friday, May 7, 2021 / Rules and Regulations persons position on the matters of fact and law involved in any hearing.
All requests for a hearing and waivers of participation must be sent to DEA
using the address information provided above.
Background and Legal Authority Under the CSA, as amended in 2015
by the Improving Regulatory Transparency for New Medical Therapies Act section 2b of Pub. L.
11489, DEA is required to commence an expedited scheduling action with respect to certain new drugs approved by the Food and Drug Administration FDA. As provided in 21 U.S.C. 811j, this expedited scheduling is required where both of the following conditions apply: 1 The Secretary of HHS has advised DEA that a New Drug Application NDA has been submitted for a drug that has a stimulant, depressant, or hallucinogenic effect on the central nervous system CNS, and that it appears that such drug has an abuse potential; and 2 the Secretary of HHS recommends that DEA control the drug in schedule II, III, IV, or V
pursuant to 21 U.S.C. 811a and b. In these circumstances, DEA is required to issue an interim final rule controlling the drug within 90 days.
Subsection j2 states that the 90-day timeframe starts the later of 1 the date DEA receives HHS scientific and medical evaluation/scheduling recommendation, or 2 the date DEA
receives notice of the NDA approval by HHS. Subsection j3 specifies that the rulemaking shall become immediately effective as an interim final rule without requiring DEA to demonstrate good cause therefore. Thus, the purpose of subsection j is to speed the process by which DEA schedules newly approved drugs that are currently either in schedule I or not controlled but which have sufficient abuse potential to warrant control so that such drugs may be marketed without undue delay following FDA approval.1
Subsection j3 further provides that the interim final rule shall give interested persons the opportunity to comment and to request a hearing. After the conclusion of such proceedings, DEA must issue a final rule in accordance with the scheduling criteria of 21 U.S.C. 811b through d and 812b.
Serdexmethylphenidate chloride 31S-1-carboxy-2-hydroxyethylaminocarbonyl-1-2R-2-1R-21 Given the parameters of subsection j, in DEAs view, it would not apply to a reformulation of a drug containing a substance currently in schedules II through V for which an NDA has recently been approved.

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methoxy-2-oxo-1-phenylethyl-1piperidinylcarbonyloxymethyl pyridinium chloride is a new molecular entity NME without CNS activity.
However, according to HHS, because serdexmethylphenidate chloride SDX
is metabolized in the large intestine to dexmethylphenidate d-MPH, a schedule II drug and a CNS stimulant, SDX is a prodrug of d-MPH.
On March 2, 2020, Commave Therapeutics S.A. submitted an NDA to FDA, in partnership with KemPharm, Inc., for a combination drug product containing SDX and d-MPH, both as chloride salts. On March 2, 2021, DEA
received notification that FDA, on the same date, approved this NDA for AZSTARYS capsules for oral use, a combination drug product containing dexmethylphenidate hydrochloride and serdexmethylphenidate chloride, under section 505c of the Federal Food, Drug, and Cosmetic Act FDCA, for the treatment of Attention Deficit Hyperactivity Disorder ADHD in patients six years of age or older.
According to the FDA-approved product label, AZSTARYS contains 28 mg/6 mg, 42 mg/9 mg, or 56 mg/12 mg of serdexmethylphenidate chloride/
dexmethylphenidate hydrochloride equivalent to 26.1 mg/5.2 mg, 39.2 mg/
7.8 mg, and 52.3 mg/10.4 mg of serdexmethylphenidate/
dexmethylphenidate, respectively.2
The 90-day time frame, as stipulated to in subsection 811j2 and discussed above, was triggered on March 2, 2021.
Therefore, DEA must issue an interim final rule controlling serdexmethylphenidate on or before May 31, 2021.
Determination To Schedule Serdexmethylphenidate On March 2, 2021, DEA received from HHS a scientific and medical evaluation entitled Basis for the Recommendation to Control Serdexmethylphenidate and its Salts in schedule IV of the Controlled Substances Act and a scheduling recommendation. Pursuant to 21 U.S.C.
811b and c, this document contained an eight-factor analysis of the abuse potential, legitimate medical use, and dependence liability of serdexmethylphenidate, along with HHSs recommendation to control serdexmethylphenidate and its salts under schedule IV of the CSA.
In response, DEA reviewed the scientific and medical evaluation and scheduling recommendation provided by HHS, along with all other relevant data, and completed its own eight-factor 2 https www.accessdata.fda.gov/drugsatfda_
docs/label/2021/212994s000lbl.pdf.

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review pursuant to 21 U.S.C. 811c.
DEA concluded that SDX meets the 21
U.S.C. 812b4 criteria for placement in schedule IV of the CSA.
Pursuant to subsection 811j, and based on HHS scheduling recommendation, the approval of the NDA by HHS/FDA, and DEAs determination, DEA is issuing this interim final rule to schedule SDX as a schedule IV controlled substance under the CSA.
Included below is a brief summary of each factor as analyzed by HHS and DEA, and as considered by DEA in its scheduling action. Please note that both DEA and HHS analyses are available in their entirety under Supporting Documents in the public docket for this interim final rule at http
www.regulations.gov, under Docket Number DEA808. Full analysis of, and citations to, the information referenced in the summary may also be found in the supporting and related material.
1. Its Actual or Relative Potential for Abuse SDX is an NME that has not been marketed in the United States or any country. Thus, evidence regarding its diversion and actual abuse is lacking.
SDX only recently became available for medical treatment, has not been diverted from legitimate sources, and individuals have not taken this substance in amounts sufficient to create a hazard to public health and safety. DEA notes that there are no reports for SDX in the National Forensic Laboratory Information System NFLIS,3 which collects drug cases submitted to and analyzed by state and local forensic laboratories.
As stated by HHS, clinical studies show that SDX, when taken by the oral route, produces effects that are similar to other stimulant drugs in schedule IV, such as phentermine. The pharmacological mechanism of action of SDX is based on its prodrug characteristics, as it must be metabolized to d-MPH to exert its effects. In clinical studies, SDX
demonstrated a lower potential for 3 NFLIS represents an important resource in monitoring illicit drug trafficking, including the diversion of legally manufactured pharmaceuticals into illegal markets. NFLIS is a comprehensive information system that includes data from forensic laboratories that handle more than 96% of an estimated 1.0 million distinct annual State and local drug analysis cases. NFLIS includes drug chemistry results from completed analyses only.
While NFLIS data is not direct evidence of abuse, it can lead to an inference that a drug has been diverted and abused. See 76 FR 77330, 77332, Dec.
12, 2011. NFLIS data were queried on March 4, 2021.

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