83 FR 63569 - List of Drug Products That Have Been Withdrawn or Removed From the Market for Reasons of Safety or Effectiveness
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 83, Issue 237 (December 11, 2018)
Food and Drug Administration
Federal Register Volume 83, Issue 237 (December 11, 2018)
| Page Range | 63569-63574 | |
| FR Document | 2018-26712 |
[Federal Register Volume 83, Number 237 (Tuesday, December 11, 2018)] [Rules and Regulations] [Pages 63569-63574] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2018-26712] ======================================================================= ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 216 [Docket No. FDA-2016-N-2462] RIN 0910-AH35 List of Drug Products That Have Been Withdrawn or Removed From the Market for Reasons of Safety or Effectiveness AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is amending its regulations to revise the list of drug products that have been withdrawn or removed from the market because such drug products or components of such drug products have been found to be unsafe or not effective. Drug products appearing on this list may not be compounded under the exemptions provided by sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act). Specifically, the final rule adds two entries to this list of drug products. DATES: This rule is effective January 10, 2019. ADDRESSES: For access to the docket to read background documents or comments received, go to https://www.regulations.gov and insert the docket number found in brackets in the heading of this final rule into the ``Search'' box and follow the prompts, and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. FOR FURTHER INFORMATION CONTACT: Alexandria Fujisaki, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 5169, Silver Spring, MD 20993-0002, 301- 796-3110. SUPPLEMENTARY INFORMATION: Table of Contents I. Executive Summary A. Purpose of the Regulatory Action B. Summary of the Major Provisions of the Regulatory Action C. Legal Authority D. Costs and Benefits II. Background A. Relevant Provisions of the Statute B. The List of Drug Products in Sec. 216.24 C. Regulatory History of the List III. Proposed Rule and Final Rule A. Presentation to the Advisory Committee B. The Proposed Rule C. The Final Rule IV. Comments on the Proposed Rule and FDA's Responses A. Comments on Proposed Entries for Inclusion on the List B. Miscellaneous Comments V. Legal Authority VI. Analysis of Environmental Impact VII. Economic Analysis of Impacts VIII. Paperwork Reduction Act of 1995 IX. Consultation and Coordination With Indian Tribal Governments X. Federalism XI. References I. Executive Summary A. Purpose of the Regulatory Action FDA is amending its regulations to revise the list of drug products that have been withdrawn or removed from the market because such drug products or components of such drug products have been found to be unsafe or not effective (referred to as ``the withdrawn or removed list'' or ``the list'') (Sec. 216.24 (21 CFR 216.24)). Drug products appearing on the withdrawn or removed list may not be compounded under the exemptions provided by sections 503A and 503B of the FD&C Act (21 U.S.C. 353a and 353b). In this final rule, the Agency is finalizing in part the proposed amendments to Sec. 216.24 set forth in the proposed rule published in the Federal Register of October 18, 2016 (81 FR 71648). B. Summary of the Major Provisions of the Regulatory Action After soliciting public comments and consulting with the FDA Pharmacy Compounding Advisory Committee (the Committee), we are adding the following entries to the list in Sec. 216.24 of drug products that have been withdrawn or removed from the market because such drug products or [[Page 63570]] components of such drug products have been found to be unsafe or not effective: Bromocriptine mesylate: All drug products containing bromocriptine mesylate for prevention of physiological lactation. Ondansetron hydrochloride: All intravenous drug products containing greater than a 16 milligram (mg) single dose of ondansetron hydrochloride. C. Legal Authority Sections 503A, 503B, and 701(a) of the FD&C Act (21 U.S.C. 353a, 353b, and 371(a)) provide the principal legal authority for this final rule. D. Costs and Benefits The Agency is not aware of routine compounding of the drug products that are the subject of this final rule. Therefore, we do not estimate any compliance costs or loss of sales as a result of the prohibition against compounding these drug products for human use. The Agency has determined that this rulemaking is not a significant regulatory action as defined by Executive Order 12866. II. Background A. Relevant Provisions of the Statute Section 503A of the FD&C Act describes the conditions that must be satisfied for human drug products compounded by a licensed pharmacist or licensed physician to be exempt from the following three sections of the FD&C Act: (1) Section 501(a)(2)(B) (21 U.S.C. 351(a)(2)(B)) (concerning current good manufacturing practice); (2) section 502(f)(1) (21 U.S.C. 352(f)(1)) (concerning the labeling of drugs with adequate directions for use); and (3) section 505 (21 U.S.C. 355) (concerning the approval of new drugs under new drug applications (NDAs) or abbreviated new drug applications (ANDAs)). In addition, section 503B of the FD&C Act describes the conditions that must be satisfied for a drug compounded for human use by or under the direct supervision of a licensed pharmacist in an outsourcing facility to be exempt from three sections of the FD&C Act: (1) Section 502(f)(1), (2) section 505, and (3) section 582 (21 U.S.C. 360eee-1) (concerning drug supply chain security). One of the conditions that must be satisfied for a drug product to qualify for the exemptions under sections 503A or 503B of the FD&C Act is that the compounder does not compound a drug product that appears on a list published by the Secretary of Health and Human Services (the Secretary) (delegated to FDA) of drug products that have been withdrawn or removed from the market because such drug products or components of such drug products have been found to be unsafe or not effective (the withdrawn or removed list) (see sections 503A(b)(1)(C), 503B(a)(4), and 503B(a)(11) of the FD&C Act). B. The List of Drug Products in Sec. 216.24 The drug products listed in the withdrawn or removed list codified at Sec. 216.24 have been withdrawn or removed from the market because they have been found to be unsafe or not effective. A drug product that is included in the withdrawn or removed list is not eligible for the exemptions provided in section 503A(a) from sections 501(a)(2)(B), 502(f)(1), and 505 of the FD&C Act. In addition, a drug that is included in the withdrawn or removed list is not eligible for the exemptions provided in section 503B(a) from sections 502(f)(1), 505, and 582 of the FD&C Act. C. Regulatory History of the List The Food and Drug Modernization Act of 1997 (Pub. L. 105-115) added section 503A to the FD&C Act. On October 8, 1998, FDA proposed a rule in the Federal Register (63 FR 54082) to establish the original withdrawn or removed list. On March 8, 1999, FDA finalized this rule (64 FR 10944), prohibiting the products described on the original list from being compounded under the exemptions provided by section 503A(a) of the FD&C Act. Following the addition of section 503B to the FD&C Act on November 27, 2013, through the enactment of the Drug Quality and Security Act (Pub. L. 113-54), FDA published a proposed rule to revise and update the list in Sec. 216.24 on July 2, 2014 (79 FR 37687); FDA published the final rule to amend Sec. 216.24 in the Federal Register of October 7, 2016 (81 FR 69668) (2016 final rule). Given that nearly identical criteria apply for a drug to be included on the list referred to in section 503A(b)(1)(C) and the list referred to in section 503B(a)(4) of the FD&C Act, the 2016 final rule added language to Sec. 216.24 clarifying that it applies for purposes of both sections 503A and 503B. III. Proposed Rule and Final Rule A. Presentation to the Advisory Committee At a meeting held on June 17 and 18, 2015 (see the Federal Register of May 22, 2015 (80 FR 29717)), FDA presented to the Committee FDA's proposal to add to the withdrawn or removed list all drug products containing more than 325 mg of acetaminophen per dosage unit, all drug products containing aprotinin, all drug products containing bromocriptine mesylate for the prevention of physiological lactation, and all intravenous drug products containing greater than a 16 mg single dose of ondansetron hydrochloride. The Committee voted in favor of including each drug product entry on the list as proposed by FDA.\1\ --------------------------------------------------------------------------- \1\ A transcript of the June 2015 Committee meeting (Ref. 1) and briefing information that includes reviews and background on the proposed entries (Ref. 2) may be found at the Dockets Management Staff (see ADDRESSES) and at https://wayback.archive-it.org/7993/20170111202622/http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PharmacyCompoundingAdvisoryCommittee/ucm431285.htm. --------------------------------------------------------------------------- B. The Proposed Rule In the Federal Register of October 18, 2016, FDA proposed to revise the withdrawn or removed list to add all drug products containing aprotinin, all drug products containing bromocriptine mesylate for the prevention of physiological lactation, and all intravenous drug products containing greater than a 16 mg single dose of ondansetron hydrochloride (October 2016 proposed rule). The addition of all drug products containing more than 325 mg of acetaminophen per dosage unit to the list was not included in the October 2016 proposed rule and remains under consideration by the Agency. C. The Final Rule The Agency has considered the public discussion and the advice provided by the Committee regarding these matters at the June 2015 meeting, as well as the October 2016 proposed rule, including the comments submitted on the proposed rule (see section IV). Based on the information before FDA and its own knowledge and expertise, FDA is adding two entries from the proposed rule to the withdrawn or removed list in Sec. 216.24. The two entries FDA is adding to Sec. 216.24 are as follows: Bromocriptine mesylate: All drug products containing bromocriptine mesylate for prevention of physiological lactation. Ondansetron hydrochloride: All intravenous drug products containing greater than a 16 mg single dose of ondansetron hydrochloride. At this time, FDA is not finalizing the entry in the proposed rule for all drug products containing aprotinin. The addition of an entry to the withdrawn or removed list for drug products containing aprotinin remains under consideration by FDA. [[Page 63571]] IV. Comments on the Proposed Rule and FDA's Responses Four comments, all from individuals, were submitted on the October 2016 proposed rule. FDA has summarized and responded to the relevant comments in the following paragraphs. A comment about ``hernia repair with mesh and plug'' has not been answered because it was not relevant to this rulemaking. Comments regarding the proposed addition of an entry to the withdrawn or removed list for aprotinin will not be answered at this time because the entry remains under consideration by FDA. To make it easier to identify the comments and FDA's responses, the word ``Comment,'' in parentheses, appears before the comment's description, and the word ``Response,'' in parentheses, appears before the Agency's response. We have numbered each comment to help distinguish between different comments. Similar comments are grouped together under the same number, and, in some cases, different subjects discussed in the same comment are separated and designated as distinct comments for purposes of FDA's response. The number assigned to each comment or comment topic is purely for organizational purposes and does not signify the comment's value or importance or the order in which the comments were received. A. Comments on Proposed Entries for Inclusion on the List 1. Bromocriptine Mesylate (Comment 1) One comment supported the proposal to include all drug products containing bromocriptine mesylate for prevention of physiological lactation on the withdrawn or removed list. (Response 1) FDA agrees with the comment. (Comment 2) FDA received one comment opposing the proposal to include all drug products containing bromocriptine mesylate for prevention of physiological lactation on the withdrawn or removed list. The comment asserts that bromocriptine mesylate offers ``significant improvements in the quantity and quality of life,'' and, although it has ``serious adverse effects,'' the benefits of bromocriptine mesylate compared to its risks ``should warrant continuous approvability.'' (Response 2) FDA disagrees with the comment. For the reasons that follow, FDA will add all drug products containing bromocriptine mesylate for prevention of physiological lactation to the list in Sec. 216.24. As a preliminary matter, the issue in this rulemaking is whether all drug products containing bromocriptine mesylate for the indication of prevention of physiological lactation were withdrawn or removed from the market because they were found to be unsafe or not effective for this indication. The criteria that must be met to place a drug product on the withdrawn or removed list are laid out in the FD&C Act. Under sections 503A and 503B of the FD&C Act, to be placed on the withdrawn or removed list, drug products must have been withdrawn or removed from the market because such drug products or components of such drug products have been found to be unsafe or not effective. As FDA previously explained in the October 2016 proposed rule, FDA withdrew approval of PARLODEL (bromocriptine mesylate, NDA 17962) for the indication of prevention of physiological lactation in a document published in the Federal Register of January 17, 1995 (60 FR 3404). At the time, PARLODEL was the only marketed drug product containing bromocriptine mesylate labeled with this indication. FDA's 2015 ``Review of Bromocriptine Mesylate for the Withdrawn or Removed List'' indicates that the 1995 withdrawal of PARLODEL for prevention of physiological lactation was based on the unfavorable benefit-risk balance of this product for this indication. See ``Review of Bromocriptine Mesylate for the Withdrawn or Removed List'' in the FDA Briefing Document for the June 17 and 18, 2015 Pharmacy Compounding Advisory Committee Meeting, available at https://wayback.archive-it.org/7993/20170113060809/http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PharmacyCompoundingAdvisoryCommittee/ucm449533.htm. In particular, in a notice published in the Federal Register on August 23, 1994 (59 FR 43347), FDA concluded that bromocriptine mesylate's risks of hypertension, seizures, and cardiovascular accidents outweighed the product's marginal benefit in preventing postpartum lactation, which can be suppressed without risk by using more conservative, nonpharmacological treatments. Withdrawal of PARLODEL's indication for the prevention of physiological lactation became effective on February 16, 1995 (60 FR 3404). FDA has determined that all drug products containing bromocriptine mesylate for prevention of physiological lactation were withdrawn or removed from the market because such products have been found to be unsafe or not effective. We note that FDA-approved drug products containing bromocriptine mesylate for other indications, such as treatment of Parkinson's disease, acromegaly, and prolactin-secreting adenomas, remain marketed. FDA's 2015 review, which included a discussion of the withdrawal of PARLODEL's indication for the prevention of physiological lactation, was presented to the Committee at the meeting held on June 17 and 18, 2015, and the Committee voted in favor of the Agency's proposal to include all drug products containing bromocriptine mesylate for the prevention of physiological lactation on the list. For these reasons, FDA proposed in the October 2016 proposed rule to include all drug products containing bromocriptine mesylate for the prevention of physiological lactation on the withdrawn or removed list. The comment offered no scientific rationale or support for its position that this drug product should not be on the list; therefore, FDA is including bromocriptine mesylate for prevention of physiological lactation on the withdrawn or removed list. 2. Ondansetron Hydrochloride (Comment 3) One comment supported the proposal to include all intravenous drug products containing greater than a 16 mg single dose of ondansetron hydrochloride on the withdrawn or removed list. (Response 3) FDA agrees with the comment. (Comment 4) FDA received one comment on the proposal to include all intravenous drug products containing greater than a 16 mg single dose of ondansetron hydrochloride suggesting ``perhaps there is more to investigate and stricter regulation of the administration of IV ondansetron hydrochloride is warranted in the future.'' (Response 4) FDA intends to monitor future approvals, withdrawals, or removals of drugs, to consider other relevant information that may suggest the need to revise the withdrawn or removed list, and to propose modifications as appropriate. In addition, members of the public can submit a citizen petition at any time under 21 CFR 10.25 and 10.30 requesting that FDA add, modify, or remove an entry on the list (with data to support their request), and FDA will consider and respond to the petition. (Comment 5) FDA received one comment opposing the proposal to include all intravenous drug products containing greater than a 16 mg single dose of ondansetron hydrochloride on [[Page 63572]] the withdrawn or removed list. The comment asserts that ondansetron hydrochloride offers ``significant improvements in the quantity and quality of life,'' and, although it has ``serious adverse effects,'' the benefits of ondansetron hydrochloride compared to its risks ``should warrant continuous approvability.'' (Response 5) FDA disagrees with the comment. For the reasons that follow, FDA will add all intravenous drug products containing greater than a 16 mg single dose of ondansetron hydrochloride to the list in Sec. 216.24. As noted earlier, the issue in this rulemaking is whether drug products containing greater than a 16 mg single dose of ondansetron hydrochloride were withdrawn or removed from the market because they were found to be unsafe or not effective. As FDA previously explained in the October 2016 proposed rule, in the Federal Register of June 10, 2015 (80 FR 32962), FDA announced its determination under 21 CFR 314.161 and 314.162(a)(2) that the NDA for Ondansetron (ondansetron hydrochloride) Injection, USP, 32 mg/50 mL, single IV dose was withdrawn from sale for reasons of safety. In particular, this product was associated with a specific type of irregular heart rhythm called QT interval prolongation, and the data suggest that any dose above the maximum recommendation of 16 mg per dose intravenously has the potential for increased risk of QT prolongation. FDA made this determination after holders of one NDA and four ANDAs voluntarily removed such products from the market and requested that FDA withdraw approval of their respective applications under 21 CFR 314.150(d). Thus, all drug products containing greater than a 16 mg single dose of ondansetron hydrochloride have been withdrawn or removed from the market because such drug products have been found to be unsafe or not effective. We note that FDA-approved drug products containing lower single doses of ondansetron hydrochloride remain marketed. FDA's review of intravenous drug products containing greater than a 16 mg single dose of ondansetron hydrochloride was presented to the Committee at the meeting held on June 17 and 18, 2015, and the Committee voted in favor of the Agency's proposal to include all intravenous drug products containing greater than a 16 mg single dose of ondansetron hydrochloride on the list. For these reasons, FDA proposed in the October 2016 proposed rule to include all intravenous drug products containing greater than a 16 mg single dose of ondansetron hydrochloride on the withdrawn or removed list. (Comment 6) FDA received one comment asserting that ondansetron hydrochloride should not be recommended for use by pregnant women because it was not approved by FDA for pregnant women. (Response 6) This comment is outside the scope of this rulemaking. Compounded drugs are not FDA approved and this rulemaking addresses the placement of certain drug products on the withdrawn or removed list, including all intravenous drug products containing greater than a 16 mg single dose of ondansetron hydrochloride. As previously noted, drugs appearing on this list may not be compounded under the exemptions provided by sections 503A and 503B of the FD&C Act. Therefore, to the extent the commenter believes that intravenous drug products containing greater than a 16 mg single dose of ondansetron hydrochloride should not be compounded for pregnant women under the exemptions provided by sections 503A and 503B of the FD&C Act, we agree. The addition of the entry FDA is finalizing regarding ondansetron hydrochloride through this rulemaking for the list in Sec. 216.24 will prohibit compounding of intravenous drug products containing greater than a 16 mg single dose of ondansetron hydrochloride under the exemptions provided by sections 503A and 503B of the FD&C Act for all patients, including pregnant women. V. Legal Authority Sections 503A and 503B of the FD&C Act provide the principal legal authority for this final rule. As described previously in section II, section 503A of the FD&C Act describes the conditions that must be satisfied for human drug products compounded by a licensed pharmacist or licensed physician to be exempt from three sections of the FD&C Act (sections 501(a)(2)(B), 502(f)(1), and 505). One of the conditions that must be satisfied to qualify for the exemptions under section 503A of the FD&C Act is that the licensed pharmacist or licensed physician does not compound a drug product that appears on a list published by FDA in the Federal Register of drug products that have been withdrawn or removed from the market because such drug products or components of such drug products have been found to be unsafe or not effective (see section 503A(b)(1)(C) of the FD&C Act). Section 503A(c)(1) of the FD&C Act also states that the Secretary shall issue regulations to implement section 503A, and that before issuing regulations to implement section 503A(b)(1)(C) pertaining to the withdrawn or removed list, among other sections, the Secretary shall convene and consult an advisory committee on compounding unless the Secretary determines that the issuance of such regulations before consultation is necessary to protect the public health.\2\ --------------------------------------------------------------------------- \2\ Note: The functions of the Secretary described herein have been delegated to FDA. --------------------------------------------------------------------------- Section 503B of the FD&C Act describes the conditions that must be satisfied for a drug compounded for human use by or under the direct supervision of a licensed pharmacist in an outsourcing facility to be exempt from three sections of the FD&C Act (sections 502(f)(1), 505, and 582). One of the conditions in section 503B of the FD&C Act that must be satisfied to qualify for the exemptions is that the drug does not appear on a list published by FDA of drugs that have been withdrawn or removed from the market because such drugs or components of such drugs have been found to be unsafe or not effective (see section 503B(a)(4)). To be eligible for the exemptions in section 503B, a drug must be compounded in an outsourcing facility in which the compounding of drugs occurs only in accordance with section 503B, including as provided in section 503B(a)(4) of the FD&C Act. Thus, sections 503A and 503B of the FD&C Act, in conjunction with our general rulemaking authority in section 701(a) of the FD&C Act (21 U.S.C. 371(a)), serve as our principal legal authority for this final rule revising FDA's regulation on the list of drug products withdrawn or removed from the market because such drug products or components of such drug products have been found to be unsafe or not effective in Sec. 216.24. VI. Analysis of Environmental Impact We have determined under 21 CFR 25.30(h) that this action is of a type that does not individually or cumulatively have a significant effect on the human environment. Therefore, neither an environmental assessment nor an environmental impact statement is required. VII. Economic Analysis of Impacts We have examined the impacts of the final rule under Executive Order 12866, Executive Order 13563, Executive Order 13771, the Regulatory Flexibility Act (5 U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Pub. L. 104-4). Executive Orders 12866 and 13563 direct us to assess all costs and benefits of available regulatory alternatives and, when regulation is [[Page 63573]] necessary, to select regulatory approaches that maximize net benefits (including potential economic, environmental, public health and safety, and other advantages; distributive impacts; and equity). Executive Order 13771 requires that the costs associated with significant new regulations ``shall, to the extent permitted by law, be offset by the elimination of existing costs associated with at least two prior regulations.'' This final rule is not a significant regulatory action as defined by Executive Order 12866 and is not subject to Executive Order 13771. The Regulatory Flexibility Act requires us to analyze regulatory options that would minimize any significant impact of a rule on small entities. Because small businesses are not expected to incur any compliance costs or loss of sales due to this regulation, we certify that the final rule will not have a significant economic impact on a substantial number of small entities. The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires us to prepare a written statement, which includes an assessment of anticipated costs and benefits, before issuing ``any rule that includes 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 one year.'' The current threshold after adjustment for inflation is $150 million, using the most current (2017) Implicit Price Deflator for the Gross Domestic Product. This final rule is not expected to result in an expenditure in any year that would meet or exceed this amount. This final rule amends Sec. 216.24 concerning human drug compounding. Specifically, the final rule adds to the list of drug products that may not be compounded under the exemptions provided by sections 503A and 503B of the FD&C Act because the drug products have been withdrawn or removed from the market because such drug products or components of such drug products have been found to be unsafe or not effective (see section II). We are adding two entries to the list: Drug products containing bromocriptine mesylate for prevention of physiological lactation and intravenous drug products containing greater than a 16 mg single dose of ondansetron hydrochloride. The Agency is not aware of routine compounding of these drug products; therefore, we do not estimate any compliance costs or loss of sales as a result of the prohibition against compounding these drugs for human use. Unless we certify that a rule will not have a significant economic impact on a substantial number of small entities, the Regulatory Flexibility Act requires us to analyze regulatory options to minimize any significant economic impact of a regulation on small entities. Most pharmacies meet the Small Business Administration definition of a small entity, which is defined as having annual sales less than $27.5 million for this industry. We are not aware of any routine compounding of the drug products that are the subject of this final rule and do not estimate any compliance costs or loss of sales to small businesses as a result of the prohibition against compounding these drug products. Therefore, we certify that this final rule will not have a significant economic impact on a substantial number of small entities. VIII. Paperwork Reduction Act of 1995 This final rule contains no collections of information. Therefore, clearance by the Office of Management and Budget under the Paperwork Reduction Act of 1995 is not required. IX. Consultation and Coordination With Indian Tribal Governments We have analyzed this rule in accordance with the principles set forth in Executive Order 13175. We have determined that the rule does not contain policies that 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. Accordingly, we conclude that the rule does not contain policies that have tribal implications as defined in the Executive Order and, consequently, a tribal summary impact statement is not required. X. Federalism We have analyzed this final rule in accordance with the principles set forth in Executive Order 13132. FDA has determined that the final rule does not contain policies that 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. Accordingly, the Agency concludes that the rule does not contain policies that have federalism implications as defined in the Executive order and, consequently, a federalism summary impact statement is not required. XI. References The following references are on display in the Dockets Management Staff (see ADDRESSES) and are available for viewing by interested persons between 9 a.m. and 4 p.m., Monday through Friday; they are also available electronically at https://www.regulations.gov. FDA has verified the website addresses, as of the date this document publishes in the Federal Register, but websites are subject to change over time. 1. Transcript for the June 17-18, 2015, Meeting of the Pharmacy Compounding Advisory Committee, available at https://wayback.archive-it.org/7993/20170111202622/http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PharmacyCompoundingAdvisoryCommittee/ucm431285.htm. 2. Briefing Information for the June 17-18, 2015, Meeting of the Pharmacy Compounding Advisory Committee, available at https://wayback.archive-it.org/7993/20170111202622/http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PharmacyCompoundingAdvisoryCommittee/ucm431285.htm. List of Subjects in 21 CFR Part 216 Drugs, Prescription drugs. Therefore, under the Federal Food, Drug, and Cosmetic Act and under authority delegated to the Commissioner of Food and Drugs, 21 CFR part 216 is amended as follows: PART 216--HUMAN DRUG COMPOUNDING 0 1. The authority citation for part 216 continues to read as follows: Authority: 21 U.S.C. 351, 352, 353a, 353b, 355, and 371. 0 2. Amend Sec. 216.24 by adding, in alphabetical order, to the list of drugs ``Bromocriptine mesylate'' and ``Ondansetron hydrochloride'' to read as follows: Sec. 216.24 Drug products withdrawn or removed from the market for reasons of safety or effectiveness. * * * * * Bromocriptine mesylate: All drug products containing bromocriptine mesylate for prevention of physiological lactation. * * * * * Ondansetron hydrochloride: All intravenous drug products containing greater than a 16 milligram single dose of ondansetron hydrochloride. * * * * * [[Page 63574]] Dated: December 4, 2018. Scott Gottlieb, Commissioner of Food and Drugs. [FR Doc. 2018-26712 Filed 12-10-18; 8:45 am] BILLING CODE 4164-01-P
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certified that this rule, when Paragraph 6010(a) Domestic VOR Federal FOR FURTHER INFORMATION CONTACT:
promulgated, does not have a significant Airways. Alexandria Fujisaki, Center for Drug
economic impact on a substantial * * * * * Evaluation and Research, Food and
number of small entities under the V–318 [Amended]
Drug Administration, 10903 New
criteria of the Regulatory Flexibility Act. Hampshire Ave., Bldg. 51, Rm. 5169,
From INT Beauce, PQ, Canada 103° and Silver Spring, MD 20993–0002, 301–
Environmental Review Quebec, PQ, Canada, 047° radials; Houlton,
ME; INT Houlton 128° and St John, NB,
796–3110.
The FAA has determined that this Canada, 267° radials; to St John. The airspace SUPPLEMENTARY INFORMATION:
action, of modifying the descriptions of within Canada is excluded.
VOR Federal airways V–318 and V–352 Table of Contents
to reflect the removal of certain route V–352 [Amended]
I. Executive Summary
segments within Canadian airspace From INT Beauce, PQ, Canada 085° and A. Purpose of the Regulatory Action
deleted by NAV CANADA, qualifies for Bangor, ME 336° radials; to Houlton, ME. B. Summary of the Major Provisions of the
categorical exclusion under the National * * * * * Regulatory Action
Environmental Policy Act and its Issued in Washington, DC, on December 3, C. Legal Authority
implementing regulations at 40 CFR part 2018. D. Costs and Benefits
1500, and in accordance with FAA II. Background
Rodger A. Dean, Jr., A. Relevant Provisions of the Statute
Order 1050.1F—Environmental Impacts: Manager, Airspace Policy Group. B. The List of Drug Products in § 216.24
Policies and Procedures, Paragraph 5–
[FR Doc. 2018–26678 Filed 12–10–18; 8:45 am] C. Regulatory History of the List
6.5a, which categorically excludes from III. Proposed Rule and Final Rule
BILLING CODE 4910–13–P
further environmental impact review A. Presentation to the Advisory Committee
rulemaking actions that designate or B. The Proposed Rule
modify classes of airspace areas, C. The Final Rule
airways, routes, and reporting points DEPARTMENT OF HEALTH AND IV. Comments on the Proposed Rule and
(see 14 CFR part 71, Designation of HUMAN SERVICES FDA’s Responses
Class A, B, C, D, and E Airspace Areas; A. Comments on Proposed Entries for
Air Traffic Service Routes; and Food and Drug Administration Inclusion on the List
B. Miscellaneous Comments
Reporting Points). This action is not
21 CFR Part 216 V. Legal Authority
expected to result in any potentially VI. Analysis of Environmental Impact
significant environmental impacts. In [Docket No. FDA–2016–N–2462] VII. Economic Analysis of Impacts
accordance with FAA Order 1050.1F, VIII. Paperwork Reduction Act of 1995
paragraph 5–2 regarding Extraordinary RIN 0910–AH35
IX. Consultation and Coordination With
Circumstances, this action has been List of Drug Products That Have Been Indian Tribal Governments
reviewed for factors and circumstances X. Federalism
Withdrawn or Removed From the XI. References
in which a normally categorically Market for Reasons of Safety or
excluded action may have a significant Effectiveness I. Executive Summary
environmental impact requiring further
analysis, and it is determined that no AGENCY: Food and Drug Administration, A. Purpose of the Regulatory Action
extraordinary circumstances exist that HHS. FDA is amending its regulations to
warrant preparation of an ACTION: Final rule. revise the list of drug products that have
environmental assessment. been withdrawn or removed from the
SUMMARY: The Food and Drug market because such drug products or
List of Subjects in 14 CFR Part 71 Administration (FDA, the Agency, or components of such drug products have
Airspace, Incorporation by reference, we) is amending its regulations to revise been found to be unsafe or not effective
Navigation (air). the list of drug products that have been (referred to as ‘‘the withdrawn or
The Amendment withdrawn or removed from the market removed list’’ or ‘‘the list’’) (§ 216.24 (21
because such drug products or CFR 216.24)). Drug products appearing
In consideration of the foregoing, the components of such drug products have
Federal Aviation Administration on the withdrawn or removed list may
been found to be unsafe or not effective. not be compounded under the
amends 14 CFR part 71 as follows: Drug products appearing on this list exemptions provided by sections 503A
may not be compounded under the and 503B of the FD&C Act (21 U.S.C.
PART 71—DESIGNATION OF CLASS A, exemptions provided by sections 503A
B, C, D, AND E AIRSPACE AREAS; AIR 353a and 353b). In this final rule, the
and 503B of the Federal Food, Drug, and Agency is finalizing in part the
TRAFFIC SERVICE ROUTES; AND Cosmetic Act (FD&C Act). Specifically,
REPORTING POINTS proposed amendments to § 216.24 set
the final rule adds two entries to this list forth in the proposed rule published in
■ 1. The authority citation for part 71 of drug products. the Federal Register of October 18, 2016
continues to read as follows: DATES: This rule is effective January 10, (81 FR 71648).
Authority: 49 U.S.C. 106(f), 106(g); 40103,
2019.
B. Summary of the Major Provisions of
40113, 40120; E.O. 10854, 24 FR 9565, 3 CFR, ADDRESSES: For access to the docket to
the Regulatory Action
1959–1963 Comp., p. 389. read background documents or
comments received, go to https:// After soliciting public comments and
§ 71.1 [Amended] www.regulations.gov and insert the consulting with the FDA Pharmacy
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■ 2. The incorporation by reference in docket number found in brackets in the Compounding Advisory Committee (the
14 CFR 71.1 of FAA Order 7400.11C, heading of this final rule into the Committee), we are adding the
Airspace Designations and Reporting ‘‘Search’’ box and follow the prompts, following entries to the list in § 216.24
Points, dated August 13, 2018 and and/or go to the Dockets Management of drug products that have been
effective September 15, 2018, is Staff, 5630 Fishers Lane, Rm. 1061, withdrawn or removed from the market
amended as follows: Rockville, MD 20852. because such drug products or
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![63574 Federal Register / Vol. 83, No. 237 / Tuesday, December 11, 2018 / Rules and Regulations
Dated: December 4, 2018. program. (2) It authorizes a new regulations (32 CFR part 199) are issued
Scott Gottlieb, Uniform Formulary process for under statutory authorities including 10
Commissioner of Food and Drugs. encouraging use of pharmaceutical U.S.C. 1074g (the Pharmacy Benefits
[FR Doc. 2018–26712 Filed 12–10–18; 8:45 am] agents in the TRICARE Pharmacy Program) and 10 U.S.C. 1079 and 1086
BILLING CODE 4164–01–P
Benefits Program that provide the best (TRICARE medical benefits). Section
clinical effectiveness by excluding 702 of NDAA–18 amends both section
coverage for particular pharmaceutical 1074g and section 1079 (the section
agents that provide very little or no 1079 amendment being automatically
DEPARTMENT OF DEFENSE clinical effectiveness relative to similar applicable to section 1086).
Office of the Secretary agents and giving preferential status to
agents that provide enhanced clinical C. Summary of Major Provisions of the
effectiveness. (3) It authorizes special Interim Final Rule
32 CFR Part 199
reimbursement methods, amounts, and The major provisions of the interim
[DOD–2018–HA–0062] procedures to encourage use of high- final rule are the following.
value products and discourage use of 1. Updating Cost-Sharing. Under the
RIN 0720–AB75 low-value products with respect to authority of section 1074g(a)(6), as
TRICARE Pharmacy Benefits Program pharmaceutical agents provided as part amended by Section 702(a) of NDAA
Reforms of medical services from authorized FY18, we are amending 32 CFR
providers. This interim final rule 199.21(i) to cross reference the statutory
AGENCY: Office of the Secretary, implements each of these three statutory changes.
Department of Defense (DoD). changes. This is being issued as an 2. Uniform Formulary Changes. Based
ACTION: Interim final rule. interim final rule in order to implement on section 1074g(a)(10), as added by
expeditiously the reforms authorized by Section 702(b)(1) of NDAA FY 18, we
SUMMARY: This interim final rule Section 702, as specifically authorized are changing the Uniform Formulary
implements Section 702 of the National by subsection (b)(3) of that section. process under 32 CFR 199.21(e) by
Defense Authorization Act for Fiscal Based on that clear Congressional authorizing the exclusion of any
Year 2018 (NDAA FY18). The law authority and intent, the Department pharmaceutical agent that provides very
makes significant changes to the finds that obtaining public comment in little or no clinical effectiveness relative
TRICARE Pharmacy Benefits Program, advance of issuing this rule is to similar agents, and preferential status
specifically it: Updates co-payment impracticable, unnecessary, and for pharmaceutical agents that have
requirements; authorizes a new process contrary to the public interest. Delaying enhanced clinical effectiveness relative
for encouraging use of pharmaceutical expeditious implementation by waiting to similar agents.
agents that provide the best clinical for public comments to this interim rule 3. Pharmaceutical Agents as Part of
effectiveness by excluding coverage for not only delays the significant cost Medical Services. Based on 10 U.S.C.
particular pharmaceutical agents that savings to the government that will be 1079(q), as added by Section 702(b)(2)
provide very little or no clinical realized through implementation but of NDAA FY18, we are changing
effectiveness relative to similar agents also continues to allow coverage of provisions of 32 CFR 199.14 to
and for giving preferential status to pharmaceutical agents that do not authorize the adoption of special
agents that provide enhanced clinical provide the best clinical effectiveness reimbursement methods, amounts and
effectiveness; and authorizes special for beneficiaries. In addition, subsection procedures to encourage the use of high
reimbursement methods, amounts, and (b)(3) of Section 702 states that ‘‘in order value products and discourage the use
procedures to encourage use or high- to implement expeditiously the reforms of low value products—both relative to
value products and discourage use of authorized . . . (A) the Secretary of similar agents—in connection with
low-value products with respect to Defense may prescribe an interim final pharmaceutical agents provided as part
pharmaceutical agents provided as part rule, (B) not later than one year after of outpatient medical services covered
of medical services from authorized prescribing the interim final rule and by TRICARE.
providers. considering public comments with
respect to such interim final rule, by II. Provisions of Interim Final Rule
DATES: This interim final rule is prescribing a final rule.’’ Clearly
effective December 11, 2018. Comments A. Updating Co-Payments
Congressional intent is to implement the
must be received by February 11, 2019. authorized reforms quickly. The interim final rule amends 32 CFR
FOR FURTHER INFORMATION CONTACT: Nonetheless, DoD invites public 199.21(i)(2), which is the paragraph of
David W. Bobb, RPh, JD, Chief, comments on this rule and is committed the TRICARE regulation that governs
Pharmacy Operations, Defense Health to considering all comments and issuing cost-sharing amounts under the
Agency (DHA), telephone (703) 681– a final rule as soon as practicable (but Pharmacy Benefits Program. The
2890. not later than one year after issuance of amended language simply cross
this interim final rule). references the statutory specifications
SUPPLEMENTARY INFORMATION:
on cost-sharing, including the table set
I. Executive Summary B. Legal Authority for the Regulatory forth in 10 U.S.C. 1074g(a)(6)(A). This
Action table lists cost sharing amounts for the
A. Purpose of the Interim Final Rule This interim final rule is under the years 2018 through 2027 for generic,
This interim final rule implements primary authority of 10 U.S.C. 1074g, formulary, and non-formulary
Section 702 of the National Defense 1079 and 1086, and Section 702 of pharmaceutical agents dispensed by
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Authorization Act for Fiscal Year 2018 NDAA–18. Specifically, section retail network pharmacies and the mail
(NDAA FY18), which does three things: 702(b)(3) of NDAA–18 authorizes DoD order pharmacy program. Two
(1) It updates cost-sharing requirements to ‘‘prescribe such changes to the exceptions are that there is a $0 cost-
for outpatient pharmaceutical regulations implementing the TRICARE share for vaccines/immunizations
prescriptions filled by retail pharmacies program . . . by prescribing an interim authorized as preventive care for
and the TRICARE mail order pharmacy final rule.’’ TRICARE program eligible beneficiaries and provided by
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Document Created: 2018-12-11 01:06:28
Document Modified: 2018-12-11 01:06:28
| Category | Regulatory Information | |
| Collection | Federal Register | |
| sudoc Class | AE 2.7: GS 4.107: AE 2.106: | |
| Publisher | Office of the Federal Register, National Archives and Records Administration | |
| Section | Rules and Regulations | |
| Action | Final rule. | |
| Dates | This rule is effective January 10, 2019. | |
| Contact | Alexandria Fujisaki, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 5169, Silver Spring, MD 20993-0002, 301- 796-3110. | |
| FR Citation | 83 FR 63569 | |
| RIN Number | 0910-AH35 | |
| CFR Associated | Drugs and Prescription Drugs |
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