Schedules of Controlled Substances: Placement of Lasmiditan in Schedule V, 5557-5562 [2020-01957]

Download as PDF jbell on DSKJLSW7X2PROD with RULES Federal Register / Vol. 85, No. 21 / Friday, January 31, 2020 / Rules and Regulations Thus, when the parties state in their ‘‘objection’’ that FDA’s ‘‘failure to indicate expressly that these substances no longer qualify in any way as ‘safe’ for use in food.. . . amounts to an arbitrary and unlawful failure to protect the safety of food,’’ it does not appear the parties have stated with particularity a specific provision of the synthetic flavoring substances order that they deem objectionable. The parties do not object to our determination to revoke the uses of the synthetic flavoring substances, and in fact in their submission, the parties stated they ‘‘applaud FDA for acknowledging that it ‘cannot consider these synthetic flavoring substances to be safe as a matter of law’ ’’ (Earthjustice submission, page 1). Rather, by asserting in their submission that FDA is being arbitrary and unlawful by failing to indicate expressly in the final rule that substances found to induce cancer cannot qualify in any way as ‘‘safe’’ for use in food, we interpret the parties’ ‘‘objection’’ to be related to the petitioners’ request to establish zero tolerances for these synthetic flavoring additives, a request we declined to act on in the final rule because such a request was not the proper subject of a food additive petition. As explained in the final rule (83 FR 50490 at 50491), a food additive petition must either propose the issuance of a regulation prescribing the conditions under which a food additive may be safely used or propose the amendment or repeal of an existing food additive regulation (sections 409(b)(1) and (i) of the FD&C Act). We explained in the final rule that we interpreted the request to establish zero tolerances for these flavoring additives as a request to issue a regulation prohibiting a substance from human food under part 189 and that this request fell outside the scope of a food additive petition because it does not propose the issuance of a new food additive regulation or the amendment or repeal of an existing food additive regulation (id.). Consequently, we did not address the zero tolerance request further in the final rule and thus this issue was not considered part of the order by regulation that revoked the uses for these synthetic flavoring additives, pursuant to section 409(c) of the FD&C Act. Therefore, because the parties failed to identify a provision of the order deemed objectionable and have also failed to raise an objection regarding the order made pursuant to section 409(c) or (d) of the FD&C Act, the provision for objections and public VerDate Sep<11>2014 16:28 Jan 30, 2020 Jkt 250001 hearing under section 409(f) of the FD&C Act does not apply.1 Finally, even though we do not think the parties’ submission legally rises to an objection under 409(f) of the FD&C Act, even if the submission was a properly raised objection, we would deny such an objection because the parties’ request amounts to the same outcome as the petitioners’ zero tolerance request and such a request falls outside the scope of the food additive petition process. IV. Conclusion After evaluating the submission from Earthjustice et al., we have concluded that the ‘‘objection’’ is not within the scope of the objections and hearing provision under section 409(f) of the FD&C Act. Therefore, we do not address the arguments related to this ‘‘objection.’’ We are confirming October 9, 2018, as the effective date of this regulation. FDA still intends to not enforce applicable requirements of the final rule with regard to food products manufactured (domestically and internationally) prior to October 9, 2020, that contain one or more of these six synthetic flavoring substances, to provide an opportunity for companies to reformulate products prior to enforcing the requirements of this final rule. 5557 Department of Health and Human Services provided the Drug Enforcement Administration (DEA) with a scheduling recommendation to place lasmiditan in schedule V of the Controlled Substances Act (CSA). In accordance with the CSA, as revised by the Improving Regulatory Transparency for New Medical Therapies Act, DEA is hereby issuing an interim final rule placing lasmiditan, including its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible, in schedule V of the CSA. Dated: January 16, 2020. Lowell J. Schiller, Principal Associate Commissioner for Policy. The effective date of this rulemaking is January 31, 2020. Interested persons may file written comments on this rulemaking in accordance with 21 U.S.C. 811(j)(3) and 21 CFR 1308.43(g). Electronic comments must be submitted, and written comments must be postmarked, on or before March 2, 2020. Commenters should be aware that the electronic Federal Docket Management System will not accept comments after 11:59 p.m. Eastern Time on the last day of the comment period. Interested persons may file a request for hearing or waiver of hearing in accordance with 21 U.S.C. 811(j)(3) and 21 CFR 1308.44. Requests for hearing and waivers of an opportunity for a hearing or to participate in a hearing must be received on or before March 2, 2020. [FR Doc. 2020–01060 Filed 1–30–20; 8:45 am] ADDRESSES: BILLING CODE 4164–01–P DEPARTMENT OF JUSTICE Drug Enforcement Administration 21 CFR Part 1308 [Docket No. DEA–558] Schedules of Controlled Substances: Placement of Lasmiditan in Schedule V Drug Enforcement Administration, Department of Justice. ACTION: Interim final rule with request for comments. AGENCY: On October 11, 2019, the U.S. Food and Drug Administration approved a new drug application for Reyvow (lasmiditan) tablets for oral use. Lasmiditan is chemically known as [2,4,6-trifluoro-N-(6-(1methylpiperidine-4-carbonyl)pyridine2-yl-benzamide]. Thereafter, the SUMMARY: 1 We note that the parties’ submission did not present any argument or evidence that FDA’s determination that the petitioners’ zero tolerance request was not the proper subject of a food additive petition, and was thus outside the scope of section 409 of the FD&C Act, was erroneous. PO 00000 Frm 00003 Fmt 4700 Sfmt 4700 DATES: To ensure proper handling of comments, please reference ‘‘Docket No. DEA–558’’ on all correspondence, including any attachments. • Electronic comments: The Drug Enforcement Administration encourages that all comments be submitted electronically through the Federal eRulemaking Portal, which provides the ability to type short comments directly into the comment field on the web page or attach a file for lengthier comments. Please go to http://www.regulations.gov and follow the online instructions at that site for submitting comments. Upon completion of your submission, you will receive a Comment Tracking Number for your comment. Please be aware that submitted comments are not instantaneously available for public view on Regulations.gov. If you have received a Comment Tracking Number, your comment has been successfully submitted and there is no need to resubmit the same comment. • Paper comments: Paper comments that duplicate the electronic submission are not necessary and are discouraged. Should you wish to mail a paper comment in lieu of an electronic comment, it should be sent via regular E:\FR\FM\31JAR1.SGM 31JAR1 5558 Federal Register / Vol. 85, No. 21 / Friday, January 31, 2020 / Rules and Regulations or express mail to: Drug Enforcement Administration, Attn: DEA Federal Register Representative/DRW, 8701 Morrissette Drive, Springfield, VA 22152. • Hearing requests: All requests for hearing and waivers of participation must be sent to: Drug Enforcement Administration, Attn: Administrator, 8701 Morrissette Drive, Springfield, Virginia 22152. All requests for hearing and waivers of participation should also be sent to: (1) Drug Enforcement Administration, Attn: Hearing Clerk/LJ, 8701 Morrissette Drive, Springfield, Virginia 22152; and (2) Drug Enforcement Administration, Attn: DEA Federal Register Representative/DRW, 8701 Morrissette Drive, Springfield, Virginia 22152. FOR FURTHER INFORMATION CONTACT: Scott A. Brinks, Diversion Control Division, Drug Enforcement Administration; Mailing Address: 8701 Morrissette Drive, Springfield, VA 22152, Telephone: (571) 362–3261. SUPPLEMENTARY INFORMATION: jbell on DSKJLSW7X2PROD with RULES Posting of Public Comments Please note that all comments received are considered part of the public record. They will, unless reasonable cause is given, be made available by the Drug Enforcement Administration (DEA) for public inspection online at http:// www.regulations.gov. Such information includes personal identifying information (such as your name, address, etc.) voluntarily submitted by the commenter. The Freedom of Information Act (FOIA) applies to all comments received. If you want to submit personal identifying information (such as your name, address, etc.) as part of your comment, but do not want it to be made publicly available, you must include the phrase ‘‘PERSONAL IDENTIFYING INFORMATION’’ in the first paragraph of your comment. You must also place all of the personal identifying information you do not want made publicly available in the first paragraph of your comment and identify what information you want redacted. If you want to submit confidential business information as part of your comment, but do not want it to be made publicly available, you must include the phrase ‘‘CONFIDENTIAL BUSINESS INFORMATION’’ in the first paragraph of your comment. You must also prominently identify the confidential business information to be redacted within the comment. Comments containing personal identifying information and confidential business information identified as VerDate Sep<11>2014 15:45 Jan 30, 2020 Jkt 250001 directed above will generally be made publicly available in redacted form. If a comment has so much confidential business information or personal identifying information that it cannot be effectively redacted, all or part of that comment may not be made publicly available. Comments posted to http:// www.regulations.gov may include any personal identifying information (such as name, address, and phone number) included in the text of your electronic submission that is not identified as directed above as confidential. An electronic copy of this document and supplemental information, including the complete Department of Health and Human Services and Drug Enforcement Administration eight-factor analyses, to this interim final rule are available at http://www.regulations.gov for easy reference. Request for Hearing, or Waiver of Participation in Hearing Pursuant to 21 U.S.C. 811(a), this action is a formal rulemaking ‘‘on the record after opportunity for a hearing.’’ Such proceedings are conducted pursuant to the provisions of the Administrative Procedure Act (APA), 5 U.S.C. 551–559. 21 CFR 1308.41– 1308.45; 21 CFR part 1316, subpart D. Interested persons may file requests for a hearing, or notices of intent to participate in a hearing, in conformity with the requirements of 21 CFR 1308.44(a) or (b), and include a statement of interest in the proceeding and the objections or issues, if any, concerning which the person desires to be heard. Any interested person may file a waiver of an opportunity for a hearing or to participate in a hearing together with a written statement regarding the interested person’s position on the matters of fact and law involved in any hearing as set forth in 21 CFR 1308.44(c). 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 Improving Regulatory Transparency for New Medical Therapies Act (Pub. L. 114–89), which was signed into law on November 25, 2015, the DEA is required to commence an expedited scheduling action with respect to certain new drugs approved by the U.S. Food and Drug Administration (FDA). As provided in 21 U.S.C. 811(j), this expedited scheduling is required where both of the following conditions apply: (1) The Secretary of the Department of Health and Human Services (Secretary of HHS PO 00000 Frm 00004 Fmt 4700 Sfmt 4700 or the Secretary) 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 recommends that DEA control the drug in schedule II, III, IV, or V, pursuant to 21 U.S.C. 811(a) and (b). In these circumstances, DEA is required to issue an interim final rule controlling the drug within 90 days. The law further states that the 90-day timeframe starts the later of: (1) The date DEA receives the HHS scientific and medical evaluation/scheduling recommendation, or (2) the date DEA receives notice of the NDA approval by HHS. In addition, the law specifies that the rulemaking shall become immediately effective as an interim final rule without requiring DEA to demonstrate good cause therefor. 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 (j) 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 subsections 21 U.S.C. 811(b), (c), and (d) and 21 U.S.C. 812(b). Lasmiditan [2,4,6-trifluoro-N-(6-(1methylpiperidine-4-carbonyl)pyridine2-yl-benzamide] is a new molecular entity with central nervous system (CNS) depressant properties. Lasmiditan is a 5-hydroxytryptamine (5–HT, serotonin) 1F receptor agonist. One of its metabolites has low GABAA channel positive allosteric activity. On October 11, 2018, Eli Lilly and Company (Sponsor) submitted an NDA to FDA for Reyvow (lasmiditan) 50 and 100 mg oral tablets. On November 4, 2019, DEA received notification that FDA, on October 11, 2019, approved the NDA for Reyvow (lasmiditan), under section 505(c) of the FDCA, for the acute treatment of migraine with or without aura in adults.2 1 Given the parameters of subsection (j), in DEA’s 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. 2 https://www.accessdata.fda.gov/drugsatfda_ docs/appletter/2019/211280Orig1s000ltr.pdf. E:\FR\FM\31JAR1.SGM 31JAR1 Federal Register / Vol. 85, No. 21 / Friday, January 31, 2020 / Rules and Regulations jbell on DSKJLSW7X2PROD with RULES Determination To Schedule Lasmiditan On November 4, 2019, DEA received from HHS a scientific and medical evaluation document (dated October 23, 2019) prepared by the FDA related to lasmiditan. This document contained an eight-factor analysis of the abuse potential of lasmiditan, along with HHS’ recommendation to control lasmiditan under schedule V of the CSA. On December 4, 2019, the DEA requested clarification from HHS regarding supporting evidence for factors 6 and 7 listed in 21 U.S.C. 811(c), as well as the third finding under 21 U.S.C. 812(b)(5), for placement of lasmiditan in schedule V. HHS responded to the DEA via a letter on January 15, 2020, with the necessary clarification. 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 review document pursuant to 21 U.S.C. 811(c). DEA concluded that lasmiditan met the 21 U.S.C. 812(b)(5) criteria for placement in schedule V of the CSA. Pursuant to subsection 811(j), and based on the HHS recommendation, NDA approval by HHS/FDA, and DEA’s determination, DEA is issuing this interim final rule to schedule lasmiditan as a schedule V 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 the 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 ‘‘DEA–558.’’ 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: As noted by HHS, lasmiditan is a new molecular entity that has not been marketed in the United States or any other country. As a result, information on the actual abuse of lasmiditan is limited. According to HHS, lasmiditan is not currently available for medical treatment, lasmiditan has not been diverted from legitimate sources, and individuals have not taken the substance in amounts sufficient to create a hazard to public health and safety. DEA further notes that there are no reports for lasmiditan in the National Forensic Laboratory Information System VerDate Sep<11>2014 15:45 Jan 30, 2020 Jkt 250001 (NFLIS),3 which collects drug identification results from drug cases submitted to and analyzed by State and local forensic laboratories. There were also no reports in STARLiMS,4 DEA’s laboratory drug evidence data system of record. Data from HHS outlined in Factors 2 and 3 demonstrate that lasmiditan is a 5-hydroxytryyptamine-1F (5–HT1F) receptor agonist. There are no 5–HT1F receptor agonists currently controlled in the CSA. Lasmiditan at the highest dose tested did produce reinforcing effects in a rat self-administration assay. Drugliking visual analog scale (VAS) for lasmiditan were significantly higher than placebo and significantly lower than the schedule IV benzodiazepine alprazolam in an abuse potential study in humans (see Factor 3). 2. Scientific Evidence of Its Pharmacological Effects, if Known: According to HHS, lasmiditan functions as a 5–HT1F receptor agonist. HHS also further stated that lasmiditan does not bind to various other receptor targets (opioid, cannabinoid, GABAergic, or other ion channels) that are typically associated with abuse. As shown by the studies summarized by HHS, lasmiditan did not produce abuse-related behaviors in the toxicity studies within mice, rats, and dogs. HHS stated that the studies demonstrating depressant effects such as weight loss, sedation, and hypothermia produced by lasmiditan could be due to its toxic concentrations of lasmiditan. In addition, results of the drug discrimination assay demonstrated that lasmiditan did not generalize to the discriminative stimulus effects of the benzodiazepine lorazepam (schedule IV); however, lasmiditan did produce reinforcing effects in the selfadministration assay. HHS described results from a Phase 1, randomized, double-blind, placebo-and active-controlled, crossover clinical trial in adult subjects who were recreational poly-drug users. The primary objective of this study was to assess the abuse potential of lasmiditan compared to alprazolam and placebo using the maximal effect score (Emax) of the at-themoment 100-mm bipolar Drug Liking VAS. 3 NFLIS is a national forensic laboratory reporting system that systematically collects results from drug chemistry analyses conducted by State and local forensic laboratories in the United States. NFLIS data were queried on 11/14/2019. 4 STARLiMS is a laboratory information management system that systematically collects results from drug chemistry analyses conducted by the DEA laboratories. On October 1, 2014, STARLiMS replaced STRIDE as the DEA laboratory drug evidence data system of record. STARLiMS data were queried on 11/18/2019. PO 00000 Frm 00005 Fmt 4700 Sfmt 4700 5559 Lasmiditan was evaluated by the comparison of Drug Liking Emax between each dose of lasmiditan and placebo. All doses of lasmiditan (100 mg, 200 mg, and 400 mg) produced significantly higher Emax than that of placebo indicating that lasmiditan has abuse potential. However, these effects of all doses of lasmiditan were significantly lower than alprazolam on mean Emax of Drug Liking. Lasmiditan 200 mg (therapeutic dose), lasmiditan 400 mg (supratherapeutic dose), and alprazolam 2 mg (43–49 percent) produced euphoric mood to a similar extent. The lower dose of lasmiditan (100 mg) produced euphoric moods in 25 percent of subjects. Alprazolam produced a feeling of relaxation in more subjects than that produced by any dose of lasmiditan. According to HHS, this pattern of adverse events (AEs) suggests that lasmiditan has a similar or slightly less potential for abuse than alprazolam. According to HHS, the Sponsor conducted eighteen Phase 1 studies in which AEs, including abuse-related AEs, were evaluated. In Phase 1, singledose studies with healthy subjects, lasmiditan produced somnolence, feeling drunk, and euphoric mood. Euphoric mood occurred in five out of twelve studies for lasmiditan, and one out of seven studies for a control group. According to HHS, overall, the data from Phase 1 studies indicated that lasmiditan had more abuse-related AEs than placebo, and alprazolam showed a greater incidence of abuse-related AEs as compared to lasmiditan in one study. HHS reviewed data from five Phase 2 and 3 studies and stated that, at therapeutic doses, lasmiditan displays abuse-related AEs to a greater extent than placebo. However, these AEs occur at a low frequency (about one percent). 3. The State of Current Scientific Knowledge Regarding the Drug or Other Substance: Appearing as a white to offwhite solid, lasmiditan is highly soluble in water and freely soluble in methanol. Per HHS, none of the steps in the manufacturing process of lasmiditan produces or utilizes substances that have a known potential for abuse, nor can they be easily modified to generate a substance with abuse potential. A high level of expertise in and knowledge of organic chemistry is required to synthesize lasmiditan. Rat studies demonstrate that lasmiditan has a half-life of approximately 31 hours. HHS also described lasmiditan pharmacokinetic data from another study conducted in beagle dogs in the fasted (overnight) state versus the fed state. The time measurement for maximal concentration E:\FR\FM\31JAR1.SGM 31JAR1 jbell on DSKJLSW7X2PROD with RULES 5560 Federal Register / Vol. 85, No. 21 / Friday, January 31, 2020 / Rules and Regulations (Tmax) was the only parameter that significantly differed between the fed (3.5 hours) and the fasted (1.25 hours) state, indicating that food has a significant slowing effect on the oral absorption of lasmiditan. A separate study in male rats was conducted to compare the plasma and brain pharmacokinetic parameters, in addition to evaluating the bioavailability of lasmiditan. Results indicate that lasmiditan crosses the blood brain barrier and collects in the brain, producing exposure levels 2.5- to 3-fold higher than those in plasma. The Tmax in both plasma and brain was reached in 30 minutes. However, the maximum serum concentration was two- and three-fold higher in the brain as compared to plasma levels following oral and IV administration, respectively. The oral bioavailability of the drug was 63.3 percent. As described by HHS, an in-vitro study was conducted to identify the human cytochrome P450 isozymes responsible for the in-vitro metabolism of lasmiditan. Results indicated the possible involvement of CYP1A2 in the production of metabolites M7, M8, and M18; CYP2D6 and CYP2C9 in the production of M7 and M18; and CYP2C19 and CYP3A4 in the production of M7 and M18. 4. Its History and Current Pattern of Abuse: Lasmiditan was approved by FDA on October 11, 2019. According to HHS, as a single active ingredient in a drug product formulation, lasmiditan has not been approved for therapeutic use in any other country. There is no information available relating to the history and current pattern of abuse of this formulation of lasmiditan or the active ingredient. As stated in Factor 1, DEA notes that there has been no diversion of lasmiditan based on NFLIS and STARLiMS data. 5. The Scope, Duration, and Significance of Abuse: As described in Factor 4, lasmiditan as a single entity has not been approved for therapeutic use outside of the United States. A search by DEA of the NFLIS and STARLiMS databases found no evidence of law enforcement encounters of lasmiditan in the United States. Based on the preclinical and clinical study data described by HHS (see Factor 2, above), and on available epidemiological data, the scope, duration, and significance of lasmiditan abuse would likely be lower than substances in schedule IV of the CSA and similar to that of a drug controlled in schedule V. 6. What, if Any, Risk There Is to the Public Health: As stated by HHS, the extent to which a drug has abuse VerDate Sep<11>2014 15:45 Jan 30, 2020 Jkt 250001 potential is considered an indication of its public health risk. Based on the preclinical and clinical study data described by HHS (see Factor 2, above), lasmiditan has abuse potential and physical or psychological dependence (Factor 7) that is lower than substances in schedule IV of the CSA and similar to that of substances controlled in schedule V. 7. Its Psychic or Physiological Dependence Liability: HHS described an animal study that was conducted to assess the withdrawal effects of lasmiditan. Based on the data from the animal study, HHS concluded that lasmiditan does not produce signs consistent with physical dependence. HHS, in its clarification letter to DEA, stated that animal data, discussed in Factor 2, suggest that lasmiditan has the potential to produce psychological dependence less than that of substances in schedule IV and similar to that of substances in schedule V. HHS further added that these circumstances of uncertain physical dependence and limited psychological dependence have likewise been observed in their analyses of other schedule V drugs. 8. Whether the Substance Is an Immediate Precursor of a Substance Already Controlled Under the CSA: Lasmiditan is not an immediate precursor of a substance that is already controlled in the CSA as defined in 21 U.S.C. 802(23). Conclusion: After considering the scientific and medical evaluation conducted by HHS, HHS’ recommendation, and DEA’s own eightfactor analysis, DEA has determined that these facts and all relevant data constitute substantial evidence of a potential for abuse of lasmiditan. As such, DEA hereby schedules lasmiditan as a controlled substance under the CSA. Determination of Appropriate Schedule 21 U.S.C. 812(b) requires the evaluation of a substance’s abuse potential, accepted medical use, and safety for use under medical supervision for scheduling under the CSA as a controlled substance. After consideration of the above eight factors determinative of control of a substance (21 U.S.C. 811(c)), and a review of the scientific and medical evaluation and scheduling recommendation provided by HHS, DEA finds that lasmiditan meets the following criteria for placement in schedule V of the CSA pursuant to 21 U.S.C. 812(b)(5). (1) Lasmiditan has a low potential for abuse relative to the drugs or other substances in Schedule IV. PO 00000 Frm 00006 Fmt 4700 Sfmt 4700 As stated by HHS, lasmiditan, a 5– HT1F receptor agonist, did not bind to receptors typically associated with abuse (e.g., opioid, cannabinoid, GABAergic). In the drug discrimination paradigm, lasmiditan did not generalize to the discriminative stimulus effects of the benzodiazepine lorazepam. Lasmiditan did, however, produce reinforcing effects in the selfadministration assay. As detailed by HHS, in a human abuse-potential study, all doses of lasmiditan produced drug-liking scores that were significantly higher than that of placebo, indicating its abuse potential. Subjects following lasmiditan reported drug-liking scores that were significantly smaller than that of alprazolam (schedule IV drug), indicating that its abuse potential is less than that of alprazolam. Lasmiditan produced abuse-related adverse events to a greater extent than that of placebo, but with low frequency (about 1 percent). (2) Lasmiditan has a currently accepted medical use in the United States. The FDA recently approved the NDA for lasmiditan oral tablets for the acute treatment of migraine with or without aura in adults. Therefore, lasmiditan has a currently accepted medical use in treatment in the United States. (3) Abuse of Lasmiditan may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in Schedule IV. As stated by HHS, based on the totality of the available scientific data, lasmiditan may lead to physical or psychological dependence that is low relative to substances in schedule IV and similar to that of substances in schedule V. Based on these findings, the Acting Administrator of DEA concludes that lasmiditan warrants control in schedule V of the CSA. 21 U.S.C. 812(b)(5). Requirements for Handling Lasmiditan Lasmiditan is subject to the CSA’s schedule V regulatory controls and administrative, civil, and criminal sanctions applicable to the manufacture, distribution, reverse distribution, dispensing, importing, exporting, research, and conduct of instructional activities and chemical analysis with, and possession involving, schedule V substances, including the following: 1. Registration. Any person who handles (manufactures, distributes, reverse distributes, dispenses, imports, exports, engages in research, or conducts instructional activities or chemical analysis with, or possesses) E:\FR\FM\31JAR1.SGM 31JAR1 jbell on DSKJLSW7X2PROD with RULES Federal Register / Vol. 85, No. 21 / Friday, January 31, 2020 / Rules and Regulations lasmiditan, or who desires to handle lasmiditan, must be registered with the DEA to conduct such activities pursuant to 21 U.S.C. 822, 823, 957, and 958, and in accordance with 21 CFR parts 1301 and 1312. Any person who currently handles or intends to handle lasmiditan, and is not registered with the DEA, must submit an application for registration and may not continue to handle lasmiditan, unless the DEA has approved that application for registration, pursuant to 21 U.S.C. 822, 823, 957, and 958, and in accordance with 21 CFR parts 1301 and 1312. 2. Disposal of Stocks. Any person who does not desire, or is not able to obtain, a schedule V registration must surrender all quantities of currently held lasmiditan, or may transfer all quantities of currently held lasmiditan to a person registered with the DEA in accordance with 21 CFR part 1317, in addition to all other applicable federal, state, local, and tribal laws. 3. Security. Lasmiditan is subject to schedule III–V security requirements and must be handled and stored in accordance with 21 CFR 1301.71– 1301.93. 4. Labeling and Packaging. All labels, labeling, and packaging for commercial containers of lasmiditan must comply with 21 U.S.C. 825 and 958(e), and be in accordance with 21 CFR part 1302. 5. Inventory. Every DEA registrant who possesses any quantity of lasmiditan must take an inventory of lasmiditan on hand, pursuant to 21 U.S.C. 827 and 958(e), and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11. Any person who becomes registered with the DEA to handle lasmiditan must take an initial inventory of all stocks of controlled substances (including lasmiditan) on hand on the date the registrant first engages in the handling of controlled substances, pursuant to 21 U.S.C. 827 and 958(e), and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11. After the initial inventory, every DEA registrant must take a new inventory of all stocks of controlled substances (including lasmiditan) on hand every two years, pursuant to 21 U.S.C. 827 and 958(e), and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11. 6. Records and Reports. Every DEA registrant must maintain records and submit reports for lasmiditan, or products containing lasmiditan, pursuant to 21 U.S.C. 827 and 958(e), and in accordance with 21 CFR parts 1304, 1312, and 1317. 7. Prescriptions. All prescriptions for lasmiditan, or products containing lasmiditan, must comply with 21 U.S.C. VerDate Sep<11>2014 15:45 Jan 30, 2020 Jkt 250001 829, and be issued in accordance with 21 CFR parts 1306 and 1311, subpart C. 8. Manufacturing and Distributing. In addition to the general requirements of the CSA and DEA regulations that are applicable to manufacturers and distributors of schedule V controlled substances, such registrants should be advised that (consistent with the foregoing considerations) any manufacturing or distribution of lasmiditan may only be for the legitimate purposes consistent with the drug’s labeling, or for research activities authorized by the Federal Food, Drug, and Cosmetic Act and the CSA. 9. Importation and Exportation. All importation and exportation of lasmiditan must be in compliance with 21 U.S.C. 952, 953, 957, and 958, and in accordance with 21 CFR part 1312. 10. Liability. Any activity involving lasmiditan not authorized by, or in violation of, the CSA or its implementing regulations, is unlawful, and may subject the person to administrative, civil, and/or criminal sanctions. Regulatory Analyses Administrative Procedure Act Section 553 of the Administrative Procedure Act (APA) (5 U.S.C.) generally requires notice and comment for rulemakings. However, 21 U.S.C. 811 provides that in cases where a certain new drug is (1) approved by HHS and (2) HHS recommends control in CSA schedule II–V, DEA shall issue an interim final rule scheduling the drug within 90 days. Additionally, the law specifies that the rulemaking shall become immediately effective as an interim final rule without requiring DEA to demonstrate good cause. Executive Orders 12866, 13563, and 13771, Regulatory Planning and Review, Improving Regulation and Regulatory Review, and Reducing Regulation and Controlling Regulatory Costs In accordance with 21 U.S.C. 811(a) and (j), this scheduling action is subject to formal rulemaking procedures performed ‘‘on the record after opportunity for a hearing,’’ which are conducted pursuant to the provisions of 5 U.S.C. 556 and 557. The CSA sets forth the procedures and criteria for scheduling a drug or other substance. Such actions are exempt from review by the Office of Management and Budget (OMB) pursuant to section 3(d)(1) of Executive Order 12866 and the principles reaffirmed in Executive Order 13563. This final rule is not an Executive Order 13771 regulatory action pursuant PO 00000 Frm 00007 Fmt 4700 Sfmt 4700 5561 to Executive Order 12866 and OMB guidance.5 Executive Order 12988, Civil Justice Reform This regulation meets the applicable standards set forth in sections 3(a) and 3(b)(2) of Executive Order 12988 to eliminate drafting errors and ambiguity, minimize litigation, provide a clear legal standard for affected conduct, and promote simplification and burden reduction. Executive Order 13132, Federalism This rulemaking does not have federalism implications warranting the application of Executive Order 13132. The rule does not have substantial direct effects on the States, on the relationship between the national government and the States, or on the distribution of power and responsibilities among the various levels of government. Executive Order 13175, Consultation and Coordination With Indian Tribal Governments This rule does not have tribal implications warranting the application of Executive Order 13175. It does not have substantial direct effects on one or more Indian tribes, on the relationship between the Federal government and Indian tribes, or on the distribution of power and responsibilities between the Federal government and Indian tribes. Regulatory Flexibility Act The Regulatory Flexibility Act (RFA) (5 U.S.C. 601–612) applies to rules that are subject to notice and comment under section 553(b) of the APA. Under 21 U.S.C. 811(j), DEA is not required to publish a general notice of proposed rulemaking. Consequently, the RFA does not apply. Unfunded Mandates Reform Act of 1995 In accordance with the Unfunded Mandates Reform Act (UMRA) of 1995, 2 U.S.C. 1501 et seq., DEA has determined that this action would not result in any Federal mandate that may result ‘‘in the expenditure by State, local, and tribal governments, in the aggregate, or by the private sector, of $100,000,000 or more (adjusted annually for inflation) in any 1 year.’’ Therefore, neither a Small Government Agency Plan nor any other action is required under UMRA of 1995. 5 Office of Mgmt. & Budget, Exec. Office of the President, Interim Guidance Implementing Section 2 of the Executive Order of January 30, 2017 Titled ‘‘Reducing Regulation and Controlling Regulatory Costs’’ (Feb. 2, 2017). E:\FR\FM\31JAR1.SGM 31JAR1 5562 Federal Register / Vol. 85, No. 21 / Friday, January 31, 2020 / Rules and Regulations Paperwork Reduction Act of 1995 This action does not impose a new collection of information requirement under the Paperwork Reduction Act of 1995. 44 U.S.C. 3501–3521. This action would not impose recordkeeping or reporting requirements on State or local governments, individuals, businesses, or organizations. An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB control number. Congressional Review Act This rule is not a major rule as defined by the Congressional Review Act (CRA), 5 U.S.C. 804. This rule will not result in: An annual effect on the economy of $100,000,000 or more; a major increase in costs or prices for consumers, individual industries, Federal, State, or local government agencies, or geographic regions; or significant adverse effects on competition, employment, investment, productivity, innovation, or on the ability of U.S.-based companies to compete with foreign-based companies in domestic and export markets. However, pursuant to the CRA, DEA has submitted a copy of this interim final rule to both Houses of Congress and to the Comptroller General. List of Subjects in 21 CFR Part 1308 Administrative practice and procedure, Drug traffic control, Reporting and recordkeeping requirements. For the reasons set out above, DEA amends 21 CFR part 1308 as follows: PART 1308—SCHEDULES OF CONTROLLED SUBSTANCES 1. The authority citation for 21 CFR part 1308 continues to read as follows: ■ Authority: 21 U.S.C. 811, 812, 871(b), unless otherwise noted. 2. Amend § 1308.15 by: a. Redesignating paragraph (e)(4) as (e)(5); ■ b. Adding new paragraph (e)(4). The addition reads as follows: ■ ■ § 1308.15 * Schedule V. * * (e) * * * * * (4) Lasmiditan [2,4,6-trifluoro-N-(6-(1-methylpiperidine-4-carbonyl)pyridine-2-yl-benzamide] ............................................................ * * * * * Dated: January 28, 2020. Uttam Dhillon, Acting Administrator. [FR Doc. 2020–01957 Filed 1–30–20; 8:45 am] BILLING CODE 4410–09–P DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT 24 CFR Parts 3280 and 3282 [Docket No. FR 6018–F–02] RIN 2502–AJ42 Streamlining and Aligning Formaldehyde Emission Control Standards for Certain Wood Products in Manufactured Home Construction With Title VI of the Toxic Substance Control Act Office of the Assistant Secretary for Housing—Federal Housing Commissioner, HUD. ACTION: Final rule. AGENCY: HUD is issuing a final rule to implement the Formaldehyde Standards for Composite Wood Products Act of 2010, which added Title VI to the Toxic Substances Control Act (TSCA). The purpose of TSCA Title VI is to reduce exposures to formaldehyde emissions from composite wood products, thereby resulting in benefits from avoided adverse health effects. In addition, HUD is removing certain aspects of the current manufactured housing formaldehyde standards requirements that are not addressed by TSCA. This final rule follows publication of a March 22, 2019, proposed rule and takes into consideration the public comments jbell on DSKJLSW7X2PROD with RULES SUMMARY: VerDate Sep<11>2014 15:45 Jan 30, 2020 Jkt 250001 received on the proposed rule. This final rule also incorporates by reference, ASTM D6007–14 and ASTM E1333–14, the current standard requirements for formaldehyde concentration and emissions rate air chamber testing. DATES: This final rule is effective March 2, 2020. The incorporation by reference of certain publications listed in the rule is approved by the Director of the Federal Register as of March 2, 2020. FOR FURTHER INFORMATION CONTACT: Teresa B. Payne, Acting Administrator, Office of Manufactured Housing Programs, Office of Housing, Department of Housing and Urban Development, 451 7th Street SW, Washington, DC 20410; telephone 202– 402–5365 (this is not a toll-free number). Persons with hearing or speech impairments may access this number via TTY by calling the Federal Relay Service at 800–877–8389 (toll-free number). SUPPLEMENTARY INFORMATION: I. Background—HUD’s March 22, 2019 Proposed Rule The Formaldehyde Standards for Composite Wood Products Act of 2010, which added TSCA Title VI (Pub. L. 111–199, enacted on July 7, 2010) (‘‘Formaldehyde Act of 2010’’), established new formaldehyde emissions standards for all hardwood plywood, medium-density fiberboard, and particleboard, including when incorporated into finished goods, that are sold, supplied, offered for sale, or manufactured (including imported) in the United States. TSCA Title VI directs HUD to update its regulation addressing formaldehyde emission standards to ensure consistency with the standards in TSCA not later than 180 days after PO 00000 Frm 00008 Fmt 4700 Sfmt 4700 2790 the Environmental Protection Agency (EPA) promulgates regulations. EPA’s final rule implementing the new requirements became effective May 22, 2017. See 81 FR 89674. On March 22, 2019, HUD published a proposed rule in the Federal Register, at 84 FR 10738, to streamline and align formaldehyde emission control standards requirements for certain wood products in manufactured homes with Title VI of the Toxic Substance Control Act. The rule proposed revising HUD’s current formaldehyde emission standards for composite wood products used in manufactured housing at 24 CFR parts 3280 and 3282 to ensure consistency with the requirements established by section 601 of TSCA and EPA requirements, including the scope of products tested and processes for testing. In addition, HUD proposed to remove certain aspects of HUD’s manufactured housing formaldehyde standards requirements that are not addressed by TSCA, including provisions for a health notice to be posted in every manufactured home, testing of panels treated after certification, and testing of certain plywood materials. Lastly, HUD’s proposed rule also added the EPA required provision for labeling finished goods by requiring labeling of each manufactured home as being ‘‘TSCA Title VI compliant’’ to the data plate of each manufactured home in 24 CFR 3280.5,1 as recommended by the 1 On October 25–27, 2016, HUD held a meeting with the Manufactured Housing Consensus Committee (MHCC). See 81 FR 66288. The Committee voted to accept a working draft of the proposed rule which cross-referenced EPA’s requirements in HUD’s regulations and removed the health hazard warning requirement in 24 CFR 3280.309. See Minutes MHCC Meeting October 25– E:\FR\FM\31JAR1.SGM 31JAR1

Agencies

[Federal Register Volume 85, Number 21 (Friday, January 31, 2020)]
[Rules and Regulations]
[Pages 5557-5562]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-01957]


=======================================================================
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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-558]


Schedules of Controlled Substances: Placement of Lasmiditan in 
Schedule V

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Interim final rule with request for comments.

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SUMMARY: On October 11, 2019, the U.S. Food and Drug Administration 
approved a new drug application for Reyvow (lasmiditan) tablets for 
oral use. Lasmiditan is chemically known as [2,4,6-trifluoro-N-(6-(1-
methylpiperidine-4-carbonyl)pyridine-2-yl-benzamide]. Thereafter, the 
Department of Health and Human Services provided the Drug Enforcement 
Administration (DEA) with a scheduling recommendation to place 
lasmiditan in schedule V of the Controlled Substances Act (CSA). In 
accordance with the CSA, as revised by the Improving Regulatory 
Transparency for New Medical Therapies Act, DEA is hereby issuing an 
interim final rule placing lasmiditan, including its salts, isomers, 
and salts of isomers whenever the existence of such salts, isomers, and 
salts of isomers is possible, in schedule V of the CSA.

DATES: The effective date of this rulemaking is January 31, 2020. 
Interested persons may file written comments on this rulemaking in 
accordance with 21 U.S.C. 811(j)(3) and 21 CFR 1308.43(g). Electronic 
comments must be submitted, and written comments must be postmarked, on 
or before March 2, 2020. Commenters should be aware that the electronic 
Federal Docket Management System will not accept comments after 11:59 
p.m. Eastern Time on the last day of the comment period.
    Interested persons may file a request for hearing or waiver of 
hearing in accordance with 21 U.S.C. 811(j)(3) and 21 CFR 1308.44. 
Requests for hearing and waivers of an opportunity for a hearing or to 
participate in a hearing must be received on or before March 2, 2020.

ADDRESSES: To ensure proper handling of comments, please reference 
``Docket No. DEA-558'' on all correspondence, including any 
attachments.
     Electronic comments: The Drug Enforcement Administration 
encourages that all comments be submitted electronically through the 
Federal eRulemaking Portal, which provides the ability to type short 
comments directly into the comment field on the web page or attach a 
file for lengthier comments. Please go to http://www.regulations.gov 
and follow the online instructions at that site for submitting 
comments. Upon completion of your submission, you will receive a 
Comment Tracking Number for your comment. Please be aware that 
submitted comments are not instantaneously available for public view on 
Regulations.gov. If you have received a Comment Tracking Number, your 
comment has been successfully submitted and there is no need to 
resubmit the same comment.
     Paper comments: Paper comments that duplicate the 
electronic submission are not necessary and are discouraged. Should you 
wish to mail a paper comment in lieu of an electronic comment, it 
should be sent via regular

[[Page 5558]]

or express mail to: Drug Enforcement Administration, Attn: DEA Federal 
Register Representative/DRW, 8701 Morrissette Drive, Springfield, VA 
22152.
     Hearing requests: All requests for hearing and waivers of 
participation must be sent to: Drug Enforcement Administration, Attn: 
Administrator, 8701 Morrissette Drive, Springfield, Virginia 22152. All 
requests for hearing and waivers of participation should also be sent 
to: (1) Drug Enforcement Administration, Attn: Hearing Clerk/LJ, 8701 
Morrissette Drive, Springfield, Virginia 22152; and (2) Drug 
Enforcement Administration, Attn: DEA Federal Register Representative/
DRW, 8701 Morrissette Drive, Springfield, Virginia 22152.

FOR FURTHER INFORMATION CONTACT: Scott A. Brinks, Diversion Control 
Division, Drug Enforcement Administration; Mailing Address: 8701 
Morrissette Drive, Springfield, VA 22152, Telephone: (571) 362-3261.

SUPPLEMENTARY INFORMATION:

Posting of Public Comments

    Please note that all comments received are considered part of the 
public record. They will, unless reasonable cause is given, be made 
available by the Drug Enforcement Administration (DEA) for public 
inspection online at http://www.regulations.gov. Such information 
includes personal identifying information (such as your name, address, 
etc.) voluntarily submitted by the commenter. The Freedom of 
Information Act (FOIA) applies to all comments received. If you want to 
submit personal identifying information (such as your name, address, 
etc.) as part of your comment, but do not want it to be made publicly 
available, you must include the phrase ``PERSONAL IDENTIFYING 
INFORMATION'' in the first paragraph of your comment. You must also 
place all of the personal identifying information you do not want made 
publicly available in the first paragraph of your comment and identify 
what information you want redacted.
    If you want to submit confidential business information as part of 
your comment, but do not want it to be made publicly available, you 
must include the phrase ``CONFIDENTIAL BUSINESS INFORMATION'' in the 
first paragraph of your comment. You must also prominently identify the 
confidential business information to be redacted within the comment.
    Comments containing personal identifying information and 
confidential business information identified as directed above will 
generally be made publicly available in redacted form. If a comment has 
so much confidential business information or personal identifying 
information that it cannot be effectively redacted, all or part of that 
comment may not be made publicly available. Comments posted to http://www.regulations.gov may include any personal identifying information 
(such as name, address, and phone number) included in the text of your 
electronic submission that is not identified as directed above as 
confidential.
    An electronic copy of this document and supplemental information, 
including the complete Department of Health and Human Services and Drug 
Enforcement Administration eight-factor analyses, to this interim final 
rule are available at http://www.regulations.gov for easy reference.

Request for Hearing, or Waiver of Participation in Hearing

    Pursuant to 21 U.S.C. 811(a), this action is a formal rulemaking 
``on the record after opportunity for a hearing.'' Such proceedings are 
conducted pursuant to the provisions of the Administrative Procedure 
Act (APA), 5 U.S.C. 551-559. 21 CFR 1308.41-1308.45; 21 CFR part 1316, 
subpart D. Interested persons may file requests for a hearing, or 
notices of intent to participate in a hearing, in conformity with the 
requirements of 21 CFR 1308.44(a) or (b), and include a statement of 
interest in the proceeding and the objections or issues, if any, 
concerning which the person desires to be heard. Any interested person 
may file a waiver of an opportunity for a hearing or to participate in 
a hearing together with a written statement regarding the interested 
person's position on the matters of fact and law involved in any 
hearing as set forth in 21 CFR 1308.44(c).
    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 Improving Regulatory Transparency for New Medical 
Therapies Act (Pub. L. 114-89), which was signed into law on November 
25, 2015, the DEA is required to commence an expedited scheduling 
action with respect to certain new drugs approved by the U.S. Food and 
Drug Administration (FDA). As provided in 21 U.S.C. 811(j), this 
expedited scheduling is required where both of the following conditions 
apply: (1) The Secretary of the Department of Health and Human Services 
(Secretary of HHS or the Secretary) 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 recommends that DEA control the drug in schedule II, 
III, IV, or V, pursuant to 21 U.S.C. 811(a) and (b). In these 
circumstances, DEA is required to issue an interim final rule 
controlling the drug within 90 days.
    The law further states that the 90-day timeframe starts the later 
of: (1) The date DEA receives the HHS scientific and medical 
evaluation/scheduling recommendation, or (2) the date DEA receives 
notice of the NDA approval by HHS. In addition, the law specifies that 
the rulemaking shall become immediately effective as an interim final 
rule without requiring DEA to demonstrate good cause therefor. 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\
---------------------------------------------------------------------------

    \1\ Given the parameters of subsection (j), in DEA's 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.
---------------------------------------------------------------------------

    Subsection (j) 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 subsections 21 
U.S.C. 811(b), (c), and (d) and 21 U.S.C. 812(b).
    Lasmiditan [2,4,6-trifluoro-N-(6-(1-methylpiperidine-4-
carbonyl)pyridine-2-yl-benzamide] is a new molecular entity with 
central nervous system (CNS) depressant properties. Lasmiditan is a 5-
hydroxytryptamine (5-HT, serotonin) 1F receptor agonist. One of its 
metabolites has low GABAA channel positive allosteric 
activity. On October 11, 2018, Eli Lilly and Company (Sponsor) 
submitted an NDA to FDA for Reyvow (lasmiditan) 50 and 100 mg oral 
tablets. On November 4, 2019, DEA received notification that FDA, on 
October 11, 2019, approved the NDA for Reyvow (lasmiditan), under 
section 505(c) of the FDCA, for the acute treatment of migraine with or 
without aura in adults.\2\
---------------------------------------------------------------------------

    \2\ https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2019/211280Orig1s000ltr.pdf.

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[[Page 5559]]

Determination To Schedule Lasmiditan

    On November 4, 2019, DEA received from HHS a scientific and medical 
evaluation document (dated October 23, 2019) prepared by the FDA 
related to lasmiditan. This document contained an eight-factor analysis 
of the abuse potential of lasmiditan, along with HHS' recommendation to 
control lasmiditan under schedule V of the CSA.
    On December 4, 2019, the DEA requested clarification from HHS 
regarding supporting evidence for factors 6 and 7 listed in 21 U.S.C. 
811(c), as well as the third finding under 21 U.S.C. 812(b)(5), for 
placement of lasmiditan in schedule V. HHS responded to the DEA via a 
letter on January 15, 2020, with the necessary clarification.
    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 review document 
pursuant to 21 U.S.C. 811(c). DEA concluded that lasmiditan met the 21 
U.S.C. 812(b)(5) criteria for placement in schedule V of the CSA.
    Pursuant to subsection 811(j), and based on the HHS recommendation, 
NDA approval by HHS/FDA, and DEA's determination, DEA is issuing this 
interim final rule to schedule lasmiditan as a schedule V 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 the 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 ``DEA-
558.'' 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: As noted by HHS, 
lasmiditan is a new molecular entity that has not been marketed in the 
United States or any other country. As a result, information on the 
actual abuse of lasmiditan is limited. According to HHS, lasmiditan is 
not currently available for medical treatment, lasmiditan has not been 
diverted from legitimate sources, and individuals have not taken the 
substance in amounts sufficient to create a hazard to public health and 
safety. DEA further notes that there are no reports for lasmiditan in 
the National Forensic Laboratory Information System (NFLIS),\3\ which 
collects drug identification results from drug cases submitted to and 
analyzed by State and local forensic laboratories. There were also no 
reports in STARLiMS,\4\ DEA's laboratory drug evidence data system of 
record.
---------------------------------------------------------------------------

    \3\ NFLIS is a national forensic laboratory reporting system 
that systematically collects results from drug chemistry analyses 
conducted by State and local forensic laboratories in the United 
States. NFLIS data were queried on 11/14/2019.
    \4\ STARLiMS is a laboratory information management system that 
systematically collects results from drug chemistry analyses 
conducted by the DEA laboratories. On October 1, 2014, STARLiMS 
replaced STRIDE as the DEA laboratory drug evidence data system of 
record. STARLiMS data were queried on 11/18/2019.
---------------------------------------------------------------------------

    Data from HHS outlined in Factors 2 and 3 demonstrate that 
lasmiditan is a 5-hydroxytryyptamine-1F (5-HT1F) receptor 
agonist. There are no 5-HT1F receptor agonists currently 
controlled in the CSA. Lasmiditan at the highest dose tested did 
produce reinforcing effects in a rat self-administration assay. Drug-
liking visual analog scale (VAS) for lasmiditan were significantly 
higher than placebo and significantly lower than the schedule IV 
benzodiazepine alprazolam in an abuse potential study in humans (see 
Factor 3).
    2. Scientific Evidence of Its Pharmacological Effects, if Known: 
According to HHS, lasmiditan functions as a 5-HT1F receptor 
agonist. HHS also further stated that lasmiditan does not bind to 
various other receptor targets (opioid, cannabinoid, GABAergic, or 
other ion channels) that are typically associated with abuse.
    As shown by the studies summarized by HHS, lasmiditan did not 
produce abuse-related behaviors in the toxicity studies within mice, 
rats, and dogs. HHS stated that the studies demonstrating depressant 
effects such as weight loss, sedation, and hypothermia produced by 
lasmiditan could be due to its toxic concentrations of lasmiditan. In 
addition, results of the drug discrimination assay demonstrated that 
lasmiditan did not generalize to the discriminative stimulus effects of 
the benzodiazepine lorazepam (schedule IV); however, lasmiditan did 
produce reinforcing effects in the self-administration assay.
    HHS described results from a Phase 1, randomized, double-blind, 
placebo-and active-controlled, crossover clinical trial in adult 
subjects who were recreational poly-drug users. The primary objective 
of this study was to assess the abuse potential of lasmiditan compared 
to alprazolam and placebo using the maximal effect score 
(Emax) of the at-the-moment 100-mm bipolar Drug Liking VAS.
    Lasmiditan was evaluated by the comparison of Drug Liking 
Emax between each dose of lasmiditan and placebo. All doses 
of lasmiditan (100 mg, 200 mg, and 400 mg) produced significantly 
higher Emax than that of placebo indicating that lasmiditan 
has abuse potential. However, these effects of all doses of lasmiditan 
were significantly lower than alprazolam on mean Emax of 
Drug Liking.
    Lasmiditan 200 mg (therapeutic dose), lasmiditan 400 mg 
(supratherapeutic dose), and alprazolam 2 mg (43-49 percent) produced 
euphoric mood to a similar extent. The lower dose of lasmiditan (100 
mg) produced euphoric moods in 25 percent of subjects. Alprazolam 
produced a feeling of relaxation in more subjects than that produced by 
any dose of lasmiditan. According to HHS, this pattern of adverse 
events (AEs) suggests that lasmiditan has a similar or slightly less 
potential for abuse than alprazolam.
    According to HHS, the Sponsor conducted eighteen Phase 1 studies in 
which AEs, including abuse-related AEs, were evaluated. In Phase 1, 
single-dose studies with healthy subjects, lasmiditan produced 
somnolence, feeling drunk, and euphoric mood. Euphoric mood occurred in 
five out of twelve studies for lasmiditan, and one out of seven studies 
for a control group. According to HHS, overall, the data from Phase 1 
studies indicated that lasmiditan had more abuse-related AEs than 
placebo, and alprazolam showed a greater incidence of abuse-related AEs 
as compared to lasmiditan in one study.
    HHS reviewed data from five Phase 2 and 3 studies and stated that, 
at therapeutic doses, lasmiditan displays abuse-related AEs to a 
greater extent than placebo. However, these AEs occur at a low 
frequency (about one percent).
    3. The State of Current Scientific Knowledge Regarding the Drug or 
Other Substance: Appearing as a white to off-white solid, lasmiditan is 
highly soluble in water and freely soluble in methanol. Per HHS, none 
of the steps in the manufacturing process of lasmiditan produces or 
utilizes substances that have a known potential for abuse, nor can they 
be easily modified to generate a substance with abuse potential. A high 
level of expertise in and knowledge of organic chemistry is required to 
synthesize lasmiditan.
    Rat studies demonstrate that lasmiditan has a half-life of 
approximately 31 hours. HHS also described lasmiditan pharmacokinetic 
data from another study conducted in beagle dogs in the fasted 
(overnight) state versus the fed state. The time measurement for 
maximal concentration

[[Page 5560]]

(Tmax) was the only parameter that significantly differed 
between the fed (3.5 hours) and the fasted (1.25 hours) state, 
indicating that food has a significant slowing effect on the oral 
absorption of lasmiditan.
    A separate study in male rats was conducted to compare the plasma 
and brain pharmacokinetic parameters, in addition to evaluating the 
bioavailability of lasmiditan. Results indicate that lasmiditan crosses 
the blood brain barrier and collects in the brain, producing exposure 
levels 2.5- to 3-fold higher than those in plasma. The Tmax 
in both plasma and brain was reached in 30 minutes. However, the 
maximum serum concentration was two- and three-fold higher in the brain 
as compared to plasma levels following oral and IV administration, 
respectively. The oral bioavailability of the drug was 63.3 percent.
    As described by HHS, an in-vitro study was conducted to identify 
the human cytochrome P450 isozymes responsible for the in-vitro 
metabolism of lasmiditan. Results indicated the possible involvement of 
CYP1A2 in the production of metabolites M7, M8, and M18; CYP2D6 and 
CYP2C9 in the production of M7 and M18; and CYP2C19 and CYP3A4 in the 
production of M7 and M18.
    4. Its History and Current Pattern of Abuse: Lasmiditan was 
approved by FDA on October 11, 2019. According to HHS, as a single 
active ingredient in a drug product formulation, lasmiditan has not 
been approved for therapeutic use in any other country. There is no 
information available relating to the history and current pattern of 
abuse of this formulation of lasmiditan or the active ingredient. As 
stated in Factor 1, DEA notes that there has been no diversion of 
lasmiditan based on NFLIS and STARLiMS data.
    5. The Scope, Duration, and Significance of Abuse: As described in 
Factor 4, lasmiditan as a single entity has not been approved for 
therapeutic use outside of the United States. A search by DEA of the 
NFLIS and STARLiMS databases found no evidence of law enforcement 
encounters of lasmiditan in the United States. Based on the preclinical 
and clinical study data described by HHS (see Factor 2, above), and on 
available epidemiological data, the scope, duration, and significance 
of lasmiditan abuse would likely be lower than substances in schedule 
IV of the CSA and similar to that of a drug controlled in schedule V.
    6. What, if Any, Risk There Is to the Public Health: As stated by 
HHS, the extent to which a drug has abuse potential is considered an 
indication of its public health risk. Based on the preclinical and 
clinical study data described by HHS (see Factor 2, above), lasmiditan 
has abuse potential and physical or psychological dependence (Factor 7) 
that is lower than substances in schedule IV of the CSA and similar to 
that of substances controlled in schedule V.
    7. Its Psychic or Physiological Dependence Liability: HHS described 
an animal study that was conducted to assess the withdrawal effects of 
lasmiditan. Based on the data from the animal study, HHS concluded that 
lasmiditan does not produce signs consistent with physical dependence. 
HHS, in its clarification letter to DEA, stated that animal data, 
discussed in Factor 2, suggest that lasmiditan has the potential to 
produce psychological dependence less than that of substances in 
schedule IV and similar to that of substances in schedule V. HHS 
further added that these circumstances of uncertain physical dependence 
and limited psychological dependence have likewise been observed in 
their analyses of other schedule V drugs.
    8. Whether the Substance Is an Immediate Precursor of a Substance 
Already Controlled Under the CSA: Lasmiditan is not an immediate 
precursor of a substance that is already controlled in the CSA as 
defined in 21 U.S.C. 802(23).
    Conclusion: After considering the scientific and medical evaluation 
conducted by HHS, HHS' recommendation, and DEA's own eight-factor 
analysis, DEA has determined that these facts and all relevant data 
constitute substantial evidence of a potential for abuse of lasmiditan. 
As such, DEA hereby schedules lasmiditan as a controlled substance 
under the CSA.

Determination of Appropriate Schedule

    21 U.S.C. 812(b) requires the evaluation of a substance's abuse 
potential, accepted medical use, and safety for use under medical 
supervision for scheduling under the CSA as a controlled substance. 
After consideration of the above eight factors determinative of control 
of a substance (21 U.S.C. 811(c)), and a review of the scientific and 
medical evaluation and scheduling recommendation provided by HHS, DEA 
finds that lasmiditan meets the following criteria for placement in 
schedule V of the CSA pursuant to 21 U.S.C. 812(b)(5).
    (1) Lasmiditan has a low potential for abuse relative to the drugs 
or other substances in Schedule IV.
    As stated by HHS, lasmiditan, a 5-HT1F receptor agonist, 
did not bind to receptors typically associated with abuse (e.g., 
opioid, cannabinoid, GABAergic). In the drug discrimination paradigm, 
lasmiditan did not generalize to the discriminative stimulus effects of 
the benzodiazepine lorazepam. Lasmiditan did, however, produce 
reinforcing effects in the self-administration assay.
    As detailed by HHS, in a human abuse-potential study, all doses of 
lasmiditan produced drug-liking scores that were significantly higher 
than that of placebo, indicating its abuse potential. Subjects 
following lasmiditan reported drug-liking scores that were 
significantly smaller than that of alprazolam (schedule IV drug), 
indicating that its abuse potential is less than that of alprazolam. 
Lasmiditan produced abuse-related adverse events to a greater extent 
than that of placebo, but with low frequency (about 1 percent).
    (2) Lasmiditan has a currently accepted medical use in the United 
States.
    The FDA recently approved the NDA for lasmiditan oral tablets for 
the acute treatment of migraine with or without aura in adults. 
Therefore, lasmiditan has a currently accepted medical use in treatment 
in the United States.
    (3) Abuse of Lasmiditan may lead to limited physical dependence or 
psychological dependence relative to the drugs or other substances in 
Schedule IV.
    As stated by HHS, based on the totality of the available scientific 
data, lasmiditan may lead to physical or psychological dependence that 
is low relative to substances in schedule IV and similar to that of 
substances in schedule V.
    Based on these findings, the Acting Administrator of DEA concludes 
that lasmiditan warrants control in schedule V of the CSA. 21 U.S.C. 
812(b)(5).

Requirements for Handling Lasmiditan

    Lasmiditan is subject to the CSA's schedule V regulatory controls 
and administrative, civil, and criminal sanctions applicable to the 
manufacture, distribution, reverse distribution, dispensing, importing, 
exporting, research, and conduct of instructional activities and 
chemical analysis with, and possession involving, schedule V 
substances, including the following:
    1. Registration. Any person who handles (manufactures, distributes, 
reverse distributes, dispenses, imports, exports, engages in research, 
or conducts instructional activities or chemical analysis with, or 
possesses)

[[Page 5561]]

lasmiditan, or who desires to handle lasmiditan, must be registered 
with the DEA to conduct such activities pursuant to 21 U.S.C. 822, 823, 
957, and 958, and in accordance with 21 CFR parts 1301 and 1312. Any 
person who currently handles or intends to handle lasmiditan, and is 
not registered with the DEA, must submit an application for 
registration and may not continue to handle lasmiditan, unless the DEA 
has approved that application for registration, pursuant to 21 U.S.C. 
822, 823, 957, and 958, and in accordance with 21 CFR parts 1301 and 
1312.
    2. Disposal of Stocks. Any person who does not desire, or is not 
able to obtain, a schedule V registration must surrender all quantities 
of currently held lasmiditan, or may transfer all quantities of 
currently held lasmiditan to a person registered with the DEA in 
accordance with 21 CFR part 1317, in addition to all other applicable 
federal, state, local, and tribal laws.
    3. Security. Lasmiditan is subject to schedule III-V security 
requirements and must be handled and stored in accordance with 21 CFR 
1301.71-1301.93.
    4. Labeling and Packaging. All labels, labeling, and packaging for 
commercial containers of lasmiditan must comply with 21 U.S.C. 825 and 
958(e), and be in accordance with 21 CFR part 1302.
    5. Inventory. Every DEA registrant who possesses any quantity of 
lasmiditan must take an inventory of lasmiditan on hand, pursuant to 21 
U.S.C. 827 and 958(e), and in accordance with 21 CFR 1304.03, 1304.04, 
and 1304.11.
    Any person who becomes registered with the DEA to handle lasmiditan 
must take an initial inventory of all stocks of controlled substances 
(including lasmiditan) on hand on the date the registrant first engages 
in the handling of controlled substances, pursuant to 21 U.S.C. 827 and 
958(e), and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11.
    After the initial inventory, every DEA registrant must take a new 
inventory of all stocks of controlled substances (including lasmiditan) 
on hand every two years, pursuant to 21 U.S.C. 827 and 958(e), and in 
accordance with 21 CFR 1304.03, 1304.04, and 1304.11.
    6. Records and Reports. Every DEA registrant must maintain records 
and submit reports for lasmiditan, or products containing lasmiditan, 
pursuant to 21 U.S.C. 827 and 958(e), and in accordance with 21 CFR 
parts 1304, 1312, and 1317.
    7. Prescriptions. All prescriptions for lasmiditan, or products 
containing lasmiditan, must comply with 21 U.S.C. 829, and be issued in 
accordance with 21 CFR parts 1306 and 1311, subpart C.
    8. Manufacturing and Distributing. In addition to the general 
requirements of the CSA and DEA regulations that are applicable to 
manufacturers and distributors of schedule V controlled substances, 
such registrants should be advised that (consistent with the foregoing 
considerations) any manufacturing or distribution of lasmiditan may 
only be for the legitimate purposes consistent with the drug's 
labeling, or for research activities authorized by the Federal Food, 
Drug, and Cosmetic Act and the CSA.
    9. Importation and Exportation. All importation and exportation of 
lasmiditan must be in compliance with 21 U.S.C. 952, 953, 957, and 958, 
and in accordance with 21 CFR part 1312.
    10. Liability. Any activity involving lasmiditan not authorized by, 
or in violation of, the CSA or its implementing regulations, is 
unlawful, and may subject the person to administrative, civil, and/or 
criminal sanctions.

Regulatory Analyses

Administrative Procedure Act

    Section 553 of the Administrative Procedure Act (APA) (5 U.S.C.) 
generally requires notice and comment for rulemakings. However, 21 
U.S.C. 811 provides that in cases where a certain new drug is (1) 
approved by HHS and (2) HHS recommends control in CSA schedule II-V, 
DEA shall issue an interim final rule scheduling the drug within 90 
days. Additionally, the law specifies that the rulemaking shall become 
immediately effective as an interim final rule without requiring DEA to 
demonstrate good cause.

Executive Orders 12866, 13563, and 13771, Regulatory Planning and 
Review, Improving Regulation and Regulatory Review, and Reducing 
Regulation and Controlling Regulatory Costs

    In accordance with 21 U.S.C. 811(a) and (j), this scheduling action 
is subject to formal rulemaking procedures performed ``on the record 
after opportunity for a hearing,'' which are conducted pursuant to the 
provisions of 5 U.S.C. 556 and 557. The CSA sets forth the procedures 
and criteria for scheduling a drug or other substance. Such actions are 
exempt from review by the Office of Management and Budget (OMB) 
pursuant to section 3(d)(1) of Executive Order 12866 and the principles 
reaffirmed in Executive Order 13563.
    This final rule is not an Executive Order 13771 regulatory action 
pursuant to Executive Order 12866 and OMB guidance.\5\
---------------------------------------------------------------------------

    \5\ Office of Mgmt. & Budget, Exec. Office of the President, 
Interim Guidance Implementing Section 2 of the Executive Order of 
January 30, 2017 Titled ``Reducing Regulation and Controlling 
Regulatory Costs'' (Feb. 2, 2017).
---------------------------------------------------------------------------

Executive Order 12988, Civil Justice Reform

    This regulation meets the applicable standards set forth in 
sections 3(a) and 3(b)(2) of Executive Order 12988 to eliminate 
drafting errors and ambiguity, minimize litigation, provide a clear 
legal standard for affected conduct, and promote simplification and 
burden reduction.

Executive Order 13132, Federalism

    This rulemaking does not have federalism implications warranting 
the application of Executive Order 13132. The rule does not have 
substantial direct effects on the States, on the relationship between 
the national government and the States, or on the distribution of power 
and responsibilities among the various levels of government.

Executive Order 13175, Consultation and Coordination With Indian Tribal 
Governments

    This rule does not have tribal implications warranting the 
application of Executive Order 13175. It does not have substantial 
direct effects on one or more Indian tribes, on the relationship 
between the Federal government and Indian tribes, or on the 
distribution of power and responsibilities between the Federal 
government and Indian tribes.

Regulatory Flexibility Act

    The Regulatory Flexibility Act (RFA) (5 U.S.C. 601-612) applies to 
rules that are subject to notice and comment under section 553(b) of 
the APA. Under 21 U.S.C. 811(j), DEA is not required to publish a 
general notice of proposed rulemaking. Consequently, the RFA does not 
apply.

Unfunded Mandates Reform Act of 1995

    In accordance with the Unfunded Mandates Reform Act (UMRA) of 1995, 
2 U.S.C. 1501 et seq., DEA has determined that this action would not 
result in any Federal mandate that may result ``in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any 1 year.'' Therefore, neither a Small Government 
Agency Plan nor any other action is required under UMRA of 1995.

[[Page 5562]]

Paperwork Reduction Act of 1995

    This action does not impose a new collection of information 
requirement under the Paperwork Reduction Act of 1995. 44 U.S.C. 3501-
3521. This action would not impose recordkeeping or reporting 
requirements on State or local governments, individuals, businesses, or 
organizations. An agency may not conduct or sponsor, and a person is 
not required to respond to, a collection of information unless it 
displays a currently valid OMB control number.

Congressional Review Act

    This rule is not a major rule as defined by the Congressional 
Review Act (CRA), 5 U.S.C. 804. This rule will not result in: An annual 
effect on the economy of $100,000,000 or more; a major increase in 
costs or prices for consumers, individual industries, Federal, State, 
or local government agencies, or geographic regions; or significant 
adverse effects on competition, employment, investment, productivity, 
innovation, or on the ability of U.S.-based companies to compete with 
foreign-based companies in domestic and export markets. However, 
pursuant to the CRA, DEA has submitted a copy of this interim final 
rule to both Houses of Congress and to the Comptroller General.

List of Subjects in 21 CFR Part 1308

    Administrative practice and procedure, Drug traffic control, 
Reporting and recordkeeping requirements.

    For the reasons set out above, DEA amends 21 CFR part 1308 as 
follows:

PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES

0
1. The authority citation for 21 CFR part 1308 continues to read as 
follows:

    Authority: 21 U.S.C. 811, 812, 871(b), unless otherwise noted.


0
2. Amend Sec.  1308.15 by:
0
a. Redesignating paragraph (e)(4) as (e)(5);
0
b. Adding new paragraph (e)(4).
    The addition reads as follows:


Sec.  1308.15  Schedule V.

* * * * *
    (e) * * *

 
 
 
(4) Lasmiditan [2,4,6-trifluoro-N-(6-(1-methylpiperidine-4-         2790
 carbonyl)pyridine-2-yl-benzamide]............................
 

* * * * *

    Dated: January 28, 2020.
Uttam Dhillon,
Acting Administrator.
[FR Doc. 2020-01957 Filed 1-30-20; 8:45 am]
BILLING CODE 4410-09-P