{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:32:27Z","timestamp":1791491547987,"version":"4.3.4"},"reference-count":96,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T00:00:00Z","timestamp":1731283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>The U.S. Food and Drug Administration (FDA) has defined narrow therapeutic index (NTI) drugs as \u201cthose drugs where small differences in dose or blood concentration may lead to serious therapeutic failures and\/or adverse drug reactions that are life\u2010threatening or result in persistent or significant disability or incapacity.\u201d FDA has undertaken efforts to develop NTI assessment criteria and enhance public confidence in generic NTI drugs through public workshops, research, and post\u2010marketing surveillance. In 2015, FDA formed the NTI Drug Working Group to develop a consistent approach to identify NTI drugs and resolve NTI\u2010related scientific and regulatory issues in a transparent and collaborative manner. One key objective of the NTI Drug Working Group is to evaluate potential NTI drugs based on five general characteristics of NTI drugs as highlighted in the case example for theophylline drug products. As of January 5, 2024, there are 33 drug products, with 14 distinct active ingredients, specified as NTI drugs in their respective product\u2010specific guidances (PSGs) for generic drug development. Future collaborative efforts with other agencies to harmonize the terms and definitions for NTI drugs may help enhance clarity and consistency during the drug development and the regulatory review process.<\/jats:p>","DOI":"10.1002\/cpt.3460","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T05:29:16Z","timestamp":1731389356000},"page":"116-129","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Narrow Therapeutic Index Drugs: <scp>FDA<\/scp> Experience, Views, and Operations"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7537-9615","authenticated-orcid":false,"given":"Mark","family":"Donnelly","sequence":"first","affiliation":[{"name":"Division of Quantitative Methods and Modeling (DQMM) Office of Research and Standards (ORS), Office of Generic Drugs (OGD), Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (FDA)  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanyan","family":"Fang","sequence":"additional","affiliation":[{"name":"Division of Quantitative Methods and Modeling (DQMM) Office of Research and Standards (ORS), Office of Generic Drugs (OGD), Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (FDA)  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajanikanth","family":"Madabushi","sequence":"additional","affiliation":[{"name":"Immediate Office (IO) Office of Clinical Pharmacology (OCP), Office of Translational Sciences (OTS), CDER, FDA  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Division of Pharmacometrics (DPM) OCP, OTS, CDER, FDA  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6887-3156","authenticated-orcid":false,"given":"Markham","family":"Luke","sequence":"additional","affiliation":[{"name":"Division of Therapeutic Performance (DTP) I ORS, OGD, CDER, FDA  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal","family":"Canterbury","sequence":"additional","affiliation":[{"name":"Division of Legal and Regulatory Support (DLRS) Office of Generic Drug Policy (OGDP), OGD, CDER, FDA  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Lerman","sequence":"additional","affiliation":[{"name":"Division of Bioequivalence (DB) I Office of Bioequivalence (OB), OGD, CDER, FDA  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paramjeet","family":"Kaur","sequence":"additional","affiliation":[{"name":"DB II OB, OGD, CDER, FDA  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devvrat","family":"Patel","sequence":"additional","affiliation":[{"name":"DB III OB, OGD, CDER, FDA  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanjie","family":"Sun","sequence":"additional","affiliation":[{"name":"Division of Biometrics (DB) VIII Office of Biostatistics, OTS, CDER, FDA  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don","family":"Schuirmann","sequence":"additional","affiliation":[{"name":"Division of Biometrics (DB) VIII Office of Biostatistics, OTS, CDER, FDA  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Dinsmore","sequence":"additional","affiliation":[{"name":"Division of Neurology (DN) II Office of Neuroscience (ON), Office of New Drugs (OND), CDER, FDA  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehul","family":"Mehta","sequence":"additional","affiliation":[{"name":"Division of Neuropsychiatric Pharmacology (DNP) OCP, OTS, CDER, FDA  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0257-9082","authenticated-orcid":false,"given":"Liang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Division of Quantitative Methods and Modeling (DQMM) Office of Research and Standards (ORS), Office of Generic Drugs (OGD), Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (FDA)  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"e_1_2_16_1_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008829403320"},{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-015-1832-0"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-1345(99)00083-4"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.28"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-1252-0_8"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare10081392"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/2042098620958910"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnmt.117.199588"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00420"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jpp\/rgab102"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-015-9753-5"},{"key":"e_1_2_16_12_1","unstructured":"Update on Japan Regulatory Agency Content current as of November 27 2023<https:\/\/www.fda.gov\/international\u2010programs\/international\u2010arrangements\/update\u2010japan\u2010regulatory\u2010agency> (2023). Cited January 5 2024."},{"key":"e_1_2_16_13_1","unstructured":"Guidance Document \u2013 Comparative Bioavailability Standards: Formulations Used for Systemic Effects<https:\/\/www.canada.ca\/en\/health\u2010canada\/services\/drugs\u2010health\u2010products\/drug\u2010products\/applications\u2010submissions\/guidance\u2010documents\/bioavailability\u2010bioequivalence\/comparative\u2010bioavailability\u2010standards\u2010formulations\u2010used\u2010systemic\u2010effects.html> (2012). Cited January 5 2024. Accessed September 1 2018."},{"key":"e_1_2_16_14_1","unstructured":"Guideline on the Investigation of Bioequivalence (Rev. 1) Committee for Medicinal Products for Human Use (CHMP) First published: January 1 2010 Last updated: March 10 2010 Legal effective date: August 1 2010 Reference Number: CPMP\/EWP\/QWP\/1401\/98 Rev. 1. 2010 August 1 2010<https:\/\/www.ema.europa.eu\/en\/documents\/scientific\u2010guideline\/guideline\u2010investigation\u2010bioequivalence\u2010rev1_en.pdf>."},{"key":"e_1_2_16_15_1","unstructured":"Product\u2010specific bioequivalence guidance<https:\/\/www.ema.europa.eu\/en\/human\u2010regulatory\/research\u2010development\/scientific\u2010guidelines\/clinical\u2010pharmacology\u2010pharmacokinetics\/product\u2010specific\u2010bioequivalence\u2010guidance>. Cited October 19 2023."},{"key":"e_1_2_16_16_1","unstructured":"Guideline for Bioequivalence Studies for Different Strengths of Oral Solid Dosage Forms English translation of Attachment 2 of Division\u2010Notification 0229 No. 10 of the Pharmaceutical and Food Safety Bureau<https:\/\/www.nihs.go.jp\/drug\/be\u2010guide(e)\/strength\/GL\u2010E_120229_ganryo.pdf> (2012). Accessed February 29 2012."},{"key":"e_1_2_16_17_1","unstructured":"Code of Federal Regulations (CFR) Title 21 Subchapter D Part 320 Subpart B Section\u00a0320.33: Criteria and evidence to assess actual or potential bioequivalence problems [21CFR320.33]<https:\/\/www.ecfr.gov\/current\/title\u201021\/chapter\u2010I\/subchapter\u2010D\/part\u2010320>. Accessed August 25 2023."},{"key":"e_1_2_16_18_1","unstructured":"SUPAC\u2010IR: Immediate\u2010Release Solid Oral Dosage Forms: Scale\u2010Up and Post\u2010Approval Changes: Chemistry Manufacturing and Controls In\u00a0Vitro Dissolution Testing and In\u00a0Vivo Bioequivalence Documentation Guidance for Industry<https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/supac\u2010ir\u2010immediate\u2010release\u2010solid\u2010oral\u2010dosage\u2010forms\u2010scale\u2010and\u2010post\u2010approval\u2010changes\u2010chemistry> (1995)."},{"key":"e_1_2_16_19_1","unstructured":"Bioavailability and Bioequivalence Studies for Orally Administered Drug Products \u2013 General Considerations Guidance for Industry Draft Guidance August 1999<https:\/\/www.regulations.gov\/document\/FDA\u20101999\u2010D\u20104088\u20100002> (1999)."},{"key":"e_1_2_16_20_1","unstructured":"Drug Interaction Studies \u2013 Study Design Data Analysis Implications for Dosing and Labeling Guidance for Industry<https:\/\/downloads.regulations.gov\/FDA\u20102006\u2010D\u20100036\u20100002\/attachment_1.pdf> (2006)."},{"key":"e_1_2_16_21_1","unstructured":"Drug Interaction Studies \u2013 Study Design Data Analysis Implications for Dosing and Labeling Guidance for Industry<https:\/\/downloads.regulations.gov\/FDA\u20102006\u2010D\u20100036\u20100032\/content.pdf> (2012)."},{"key":"e_1_2_16_22_1","unstructured":"Meeting of the Pharmaceutical Science and Clinical Pharmacology Advisory Committee<https:\/\/wayback.archive\u2010it.org\/7993\/20170403224116\/https:\/\/www.fda.gov\/AdvisoryCommittees\/CommitteesMeetingMaterials\/Drugs\/AdvisoryCommitteeforPharmaceuticalScienceandClinicalPharmacology\/ucm201700.htm> (2012)."},{"key":"e_1_2_16_23_1","unstructured":"Meeting of the Pharmaceutical Science and Clinical Pharmacology Advisory Committee<https:\/\/wayback.archive\u2010it.org\/7993\/20170403224114\/https:\/\/www.fda.gov\/AdvisoryCommittees\/CommitteesMeetingMaterials\/Drugs\/AdvisoryCommitteeforPharmaceuticalScienceandClinicalPharmacology\/ucm240583.htm> (2011)."},{"key":"e_1_2_16_24_1","unstructured":"Citizen Petition to FDA Docket: FDA\u20102020\u2010P\u20101247 Final Response Letter from FDA CDER to Belcher Pharmaceuticals LLC. (FDA\u20102020\u2010P\u20101247\u20100006)<https:\/\/www.regulations.gov\/document\/FDA\u20102020\u2010P\u20101247\u20100006> (2023)."},{"key":"e_1_2_16_25_1","unstructured":"Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA Guidance for Industry<https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/bioequivalence\u2010studies\u2010pharmacokinetic\u2010endpoints\u2010drugs\u2010submitted\u2010under\u2010abbreviated\u2010new\u2010drug> (2021)."},{"key":"e_1_2_16_26_1","unstructured":"Generic Competition and Drug Prices Content current as of September 12 2022<https:\/\/www.fda.gov\/about\u2010fda\/center\u2010drug\u2010evaluation\u2010and\u2010research\u2010cder\/generic\u2010competition\u2010and\u2010drug\u2010prices> (2022)."},{"key":"e_1_2_16_27_1","unstructured":"FDA Drug Competition Action Plan: Helps remove barriers to generic drug development and market entry so that consumers can get access to needed medicines Content current as of June 9 2023<https:\/\/www.fda.gov\/drugs\/guidance\u2010compliance\u2010regulatory\u2010information\/fda\u2010drug\u2010competition\u2010action\u2010plan> (2023)."},{"key":"e_1_2_16_28_1","unstructured":"FDA Orange Book Preface Approved Drug Products with Therapeutic Equivalence Evaluations Preface to 43rd Edition Content current as of January 24 2023<https:\/\/www.fda.gov\/drugs\/development\u2010approval\u2010process\u2010drugs\/orange\u2010book\u2010preface> (2023)."},{"key":"e_1_2_16_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2022.03.012"},{"key":"e_1_2_16_30_1","unstructured":"Code of Federal Regulations (CFR) Title 21 Subchapter D Part 314 Subpart A Section\u00a0314.3(b): Definitions [21CFR314.3(b)]<https:\/\/www.ecfr.gov\/current\/title\u201021\/chapter\u2010I\/subchapter\u2010D\/part\u2010314\/subpart\u2010A\/section\u2010314.3> (2023)."},{"key":"e_1_2_16_31_1","unstructured":"Product\u2010Specific Guidances for Generic Drug Development Content current as of November 21 2022<https:\/\/www.fda.gov\/drugs\/guidances\u2010drugs\/product\u2010specific\u2010guidances\u2010generic\u2010drug\u2010development> (2022)."},{"key":"e_1_2_16_32_1","unstructured":"Draft product\u2010specific guidance on warfarin sodium oral tablet 1\u00a0mg 2 mg 2.5 mg 3 mg 4 mg 5 mg 6 mg 7.5 mg and 10 mg referencing NDA 009218 Recommended Dec 2012<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/psg\/Warfarin_Sodium_tab_09218_RC12\u201012.pdf> (2012)."},{"key":"e_1_2_16_33_1","unstructured":"Statistical Approaches to Establishing Bioequivalence<https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/statistical\u2010approaches\u2010establishing\u2010bioequivalence\u20100> (2022)."},{"key":"e_1_2_16_34_1","unstructured":"FDA Q&A: Generic Versions of Narrow Therapeutic Index Drugs National Survey of Pharmacists' Substitution Beliefs and Practices<https:\/\/globalforum.diaglobal.org\/issue\/july\u20102019\/fda\u2010qa\u2010generic\u2010versions\u2010of\u2010narrow\u2010therapeutic\u2010index\u2010drugs\u2010national\u2010survey\u2010of\u2010pharmacists\u2010substitution\u2010beliefs\u2010and\u2010practices\/> (2019)."},{"key":"e_1_2_16_35_1","unstructured":"FDA Webinar: \u201cFDA Drug Topics: Understanding Generic Narrow Therapeutic Index Drugs\u201d FDA's Division of Drug Information in the Center for Drug Evaluation and Research (CDER) Presented by Wenlei Jiang Ph.D. on November 1 2022 content current as of January 6 2023<https:\/\/www.fda.gov\/about\u2010fda\/fda\u2010pharmacy\u2010student\u2010experiential\u2010program\/understanding\u2010generic\u2010narrow\u2010therapeutic\u2010index\u2010drugs;https:\/\/www.fda.gov\/media\/162779\/download> (2022)."},{"key":"e_1_2_16_36_1","unstructured":"Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs \u2013 General Considerations Guidance for Industry<https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/bioavailability\u2010studies\u2010submitted\u2010ndas\u2010or\u2010inds\u2010general\u2010considerations> (2022)."},{"key":"e_1_2_16_37_1","unstructured":"Citizen Petition to FDA Docket: FDA\u20102020\u2010P\u20101247 Citizen Petition from Belcher Pharmaceuticals LLC Submitted on April 3 2020<https:\/\/www.regulations.gov\/document\/FDA\u20102020\u2010P\u20101247\u20100001> (2020)."},{"key":"e_1_2_16_38_1","unstructured":"Dissolution Testing and Acceptance Criteria for Immediate\u2010Release Solid Oral Dosage Form Drug Products Containing High Solubility Drug Substances Guidance for Industry(2018)."},{"key":"e_1_2_16_39_1","unstructured":"Product\u2010Specific Guidance Meetings Between FDA and ANDA Applicants Under GDUFA Guidance for Industry<https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/product\u2010specific\u2010guidance\u2010meetings\u2010between\u2010fda\u2010and\u2010anda\u2010applicants\u2010under\u2010gdufa> (2023)."},{"key":"e_1_2_16_40_1","unstructured":"Code of Federal Regulations (CFR) Title 21 Subchapter D Part 320 Subpart B Section\u00a0320.24: Types of evidence to measure bioavailability or establish bioequivalence [21CFR320.24]<https:\/\/www.ecfr.gov\/current\/title\u201021\/chapter\u2010I\/subchapter\u2010D\/part\u2010320\/subpart\u2010B\/section\u2010320.24> (2023)."},{"key":"e_1_2_16_41_1","unstructured":"Citizen Petition to FDA Docket: FDA\u20102019\u2010P\u20103545 Response Letter from FDA CDER to Axinn Veltrop & Harkrider LLP (FDA\u20102019\u2010P\u20103545\u20100008) Posted December 19 2019<https:\/\/www.regulations.gov\/document\/FDA\u20102019\u2010P\u20103545\u20100008> (2019)."},{"key":"e_1_2_16_42_1","unstructured":"Citizen Petition to FDA Docket: FDA\u20102015\u2010P\u20104566 Final Response from FDA CDER to Buchanan Ingersoll & Rooney PC (FDA\u20102015\u2010P\u20104566\u20100005) Posted August 30 2017<https:\/\/www.regulations.gov\/document\/FDA\u20102015\u2010P\u20104566\u20100005> (2017)."},{"key":"e_1_2_16_43_1","unstructured":"FY2015 Regulatory Science Research Report: Narrow Therapeutic Index Drugs Content current as of May 9 2017<https:\/\/www.fda.gov\/industry\/generic\u2010drug\u2010user\u2010fee\u2010amendments\/fy2015\u2010regulatory\u2010science\u2010research\u2010report\u2010narrow\u2010therapeutic\u2010index\u2010drugs> (2015)."},{"key":"e_1_2_16_44_1","unstructured":"FY2016 Regulatory Science Report: Postmarket: Patient Substitution Studies Content current as of March 28 2017<https:\/\/www.fda.gov\/industry\/generic\u2010drug\u2010user\u2010fee\u2010amendments\/fy2016\u2010regulatory\u2010science\u2010report\u2010postmarket\u2010patient\u2010substitution\u2010studies> (2016)."},{"key":"e_1_2_16_45_1","unstructured":"FY2022 GDUFA Science and Research Report Patient Substitution of Generic Drugs<https:\/\/www.fda.gov\/media\/164843\/download> (2022)."},{"key":"e_1_2_16_46_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.17645"},{"key":"e_1_2_16_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1743"},{"key":"e_1_2_16_48_1","unstructured":"Real\u2010world Evidence from a Narrow Therapeutic Index Product (Levothyroxine) Reflects the Therapeutic Equivalence of Generic Drug Products Content current as of November 19 2020<https:\/\/www.fda.gov\/drugs\/news\u2010events\u2010human\u2010drugs\/real\u2010world\u2010evidence\u2010narrow\u2010therapeutic\u2010index\u2010product\u2010levothyroxine\u2010reflects\u2010therapeutic\u2010equivalence> (2020)."},{"key":"e_1_2_16_49_1","unstructured":"Questions and Answers on FDA's Adverse Event Reporting System (FAERS) Content current as of June 4 2018<https:\/\/www.fda.gov\/drugs\/surveillance\/questions\u2010and\u2010answers\u2010fdas\u2010adverse\u2010event\u2010reporting\u2010system\u2010faers> (2018)."},{"key":"e_1_2_16_50_1","unstructured":"FDA's Sentinel Initiative Content current as of February 2 2023<https:\/\/www.fda.gov\/safety\/fdas\u2010sentinel\u2010initiative> (2023)."},{"key":"e_1_2_16_51_1","unstructured":"Science & Research Office of Generic Drugs (OGD)<https:\/\/www.fda.gov\/drugs\/generic\u2010drugs\/science\u2010research>."},{"key":"e_1_2_16_52_1","unstructured":"Citizen Petition to FDA Docket: FDA\u20102011\u2010P\u20100654 Request to Disapprove Abbreviated New Drug Application 78\u2013868 Filed by Apotex Inc. for Generic Tizanidine Hydrochloride Capsules\u2010CLOSED<https:\/\/www.regulations.gov\/docket\/FDA\u20102011\u2010P\u20100654> (2011)."},{"key":"e_1_2_16_53_1","unstructured":"Citizen Petition to FDA Docket: FDA\u20102014\u2010P\u20102193 Requests that the FDA take the actions with respect to the bioequivalence criteria required of abbreviated new drug applications (\u201cAND As\u201d) for dalfampridine filed under section\u00a0505(j) of the FDCA citing Acorda's product Ampyra as the reference listed drug (\"RLD\")<https:\/\/www.regulations.gov\/docket\/FDA\u20102014\u2010P\u20102193> (2014)."},{"key":"e_1_2_16_54_1","unstructured":"Generic Drug User Fee Amendments III (GDUFA III) Reauthorization Performance Goals and Program Enhancements Fiscal Years 2023\u20132027<https:\/\/www.fda.gov\/media\/153631\/download>."},{"key":"e_1_2_16_55_1","unstructured":"M9 Biopharmaceutics Classification System\u2010Based Biowaivers Guidance for Industry<https:\/\/www.fda.gov\/media\/148472\/download> (2021)."},{"key":"e_1_2_16_56_1","unstructured":"Draft product\u2010specific guidance for clonazepam oral tablet referencing NDA 017533 Finalized August 2017<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/psg\/Clonazepam_Oral%20Tablet_RLD%2017533_Final%2008\u201017.pdf> (2017)."},{"key":"e_1_2_16_57_1","unstructured":"M13A bioequivalence for immediate\u2010release solid oral dosage forms January 2023<https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/m13a\u2010bioequivalence\u2010immediate\u2010release\u2010solid\u2010oral\u2010dosage\u2010forms> (2024). Cited August 8 2024."},{"key":"e_1_2_16_58_1","unstructured":"Draft product\u2010specific guidance for theophylline for extended\u2010release tablets 400 mg and 600 mg referencing ANDA 040560 Recommended Feb 2010; revised Aug 2020<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/psg\/PSG_085328\u2010TabER\u2010600MG.pdf> (2020)."},{"key":"e_1_2_16_59_1","unstructured":"Draft product\u2010specific guidance for theophylline for extended\u2010release capsules 100 mg 200 mg 300 mg and 400 mg referencing ANDA 081034 Recommended Feb 2010; revised Aug 2020<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/psg\/PSG_087942.pdf> (2020)."},{"key":"e_1_2_16_60_1","unstructured":"Draft product\u2010specific guidance for theophylline for extended\u2010release tablets 100 mg 200 mg 300 mg and 450 mg referencing ANDA 090430 ANDA 086998 or ANDA 085328 Recommended Feb 2010; Withdrawn Aug 2020; Revised May 2022<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/psg\/PSG_085328.pdf> (2022)."},{"key":"e_1_2_16_61_1","unstructured":"Draft product\u2010specific guidance for cyclosporin oral capsules 25 mg 50 mg and 100 mg referencing NDA 050625 Recommended Mar 2015; Revised Apr 2016<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/psg\/Cyclosporine_Oral%20capsule_RLD%20050625_RV04\u201016.pdf> (2016)."},{"key":"e_1_2_16_62_1","unstructured":"Draft product\u2010specific guidance for cyclosporin oral capsules 25 mg and 100 mg referencing NDA 050715 Recommended Mar 2015; Revised Apr 2016<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/psg\/Cyclosporine_Oral%20capsule_RLD%20050715_RV04\u201016.pdf> (2016)."},{"key":"e_1_2_16_63_1","unstructured":"Draft product\u2010specific guidance for cyclosporin ophthalmic emulsion 0.1% referencing NDA 214965 Recommended Aug 2022<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/psg\/PSG_214965.pdf> (2022)."},{"key":"e_1_2_16_64_1","unstructured":"Draft product\u2010specific guidance for cyclosporin ophthalmic emulsion 0.05% referencing NDA 050790 Recommended Jun 2013; Revised Feb 2016; Oct 2016<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/psg\/Cyclosporine_ophthalmic%20emulsion_RLD%20050790_RV09\u201016.pdf> (2016)."},{"key":"e_1_2_16_65_1","unstructured":"Draft product\u2010specific guidance for cyclosporin ophthalmic solution\/drops 0.09% referencing NDA 210913 Recommended May 2019<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/psg\/Cyclosporine%20ophthalmic%20solution%200.09%20NDA%20210913%20PSG%20Page%20RC%20May%202019.pdf> (2019)."},{"key":"e_1_2_16_66_1","unstructured":"Product labeling for AFINITOR\u00ae (everolimus) oral tablets and AFINITOR DISPERZ\u00ae (everolimus tablets for oral suspension) Updated April 2021<https:\/\/dailymed.nlm.nih.gov\/dailymed\/drugInfo.cfm?setid=2150f73a\u2010179b\u20104afc\u2010b8ce\u201067c85cc72f04> (2021)."},{"key":"e_1_2_16_67_1","unstructured":"Draft product\u2010specific guidance for everolimus oral tablet for suspension 2 mg 3 mg and 5 mg referencing NDA 203985 Recommended Oct 2017<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/psg\/Everolimus_oral%20tablet%20for%20suspension_NDA%20203985_RC08\u201017.pdf> (2017)."},{"key":"e_1_2_16_68_1","unstructured":"Draft product\u2010specific guidance for everolimus oral tablet 2.5 mg 5 mg 7.5 mg and 10 mg referencing NDA 022334 Recommended Sept 2015; Revised Mar 2017 Nov 2018<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/psg\/Everolimus_draft_Oral%20tab_RLD%2022334_RC11\u201018.pdf> (2018)."},{"key":"e_1_2_16_69_1","unstructured":"Product labeling for ZORTRESS\u00ae (everolimus) oral tablets Updated May 16 2022<https:\/\/dailymed.nlm.nih.gov\/dailymed\/drugInfo.cfm?setid=e082a024\u20107850\u2010400b\u2010a5c2\u20102a140612562a> (2022)."},{"key":"e_1_2_16_70_1","unstructured":"Draft product\u2010specific guidance for everolimus oral tablet 0.25 mg 0.5 mg 0.75 mg and 1 mg referencing NDA 021560 Recommended Jun 2016; Revised Jun 2020<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/psg\/PSG_021560.pdf> (2020)."},{"key":"e_1_2_16_71_1","unstructured":"Draft product\u2010specific guidance for dabigatran etexilate mesylate oral capsules 75 mg 110 mg 150 mg referencing NDA 022512 Recommended Jun 2012; Revised Sept 2015 Jul 2017<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/psg\/Dabigatran%20etexilate%20mesylate_oral%20capsule_NDA%20022512_RV05\u201017.pdf> (2017)."},{"key":"e_1_2_16_72_1","unstructured":"Draft product\u2010specific guidance for rivaroxaban oral tablets 2.5 mg 10 mg 15 mg and 20 mg referencing NDA 022406 Recommended Sep 2015; Revised Aug 2020<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/psg\/PSG_022406.pdf> (2020)."},{"key":"e_1_2_16_73_1","unstructured":"Draft product\u2010specific guidance for edoxaban tosylate oral tablets 15 mg 30 mg and 60 mg referencing NDA 206316 Recommended May 2017; Revised Mar 2020<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/psg\/PSG_206316.pdf> (2020)."},{"key":"e_1_2_16_74_1","unstructured":"Acenocoumarol tablet 1 mg and 4 mg product\u2010specific bioequivalence guidance \u2013 First version First published: September 13 2021 Last updated: September 22 2021 Reference Number: EMA\/CHMP\/512475\/2020 Corr. Legal effective date: April 1 2022<https:\/\/www.ema.europa.eu\/en\/documents\/scientific\u2010guideline\/acenocoumarol\u2010tablet\u20101\u2010mg\u2010and\u20104\u2010mg\u2010product\u2010specific\u2010bioequivalence\u2010guidance\u2010first\u2010version_en.pdf>. Cited January 5 2024 (2022)."},{"key":"e_1_2_16_75_1","unstructured":"Colchicine tablet 0.5 mg and 1 mg product\u2010specific bioequivalence guidance First published: October 15 2019 Reference Number: EMA\/CHMP\/35552\/2019 Legal effective date: April 1 2020. 2020 August 22 2024<https:\/\/www.ema.europa.eu\/en\/documents\/scientific\u2010guideline\/colchicine\u2010tablet\u201005\u2010mg\u2010and\u20101\u2010mg\u2010product\u2010specific\u2010bioequivalence\u2010guidance_en.pdf> (2020)."},{"key":"e_1_2_16_76_1","unstructured":"Everolimus tablets 0.25 0.5 0.75 and 1 mg; 2.5 5 and 10 mg dispersible tablets 0.1 and 0.25 mg; 2 3 and 5 mg product\u2010specific bioequivalence guidance (draft) Draft: consultation closed First published: May 2 2016 Last updated: May 2 2016 Consultation dates: May 2 2016 to July 31 2016 Reference Number: EMA\/CHMP\/154772\/2016<https:\/\/www.ema.europa.eu\/en\/documents\/scientific\u2010guideline\/draft\u2010everolimus\u2010tablets\u2010025\u201005\u2010075\u2010and\u20101mg\u201025\u20105\u2010and\u201010mg\u2010dispersible\u2010tablets\u201001\u2010and\u2010025mg\u20102\u20103\u2010and\u20105mg\u2010product\u2010specific\u2010bioequivalence\u2010guidance_en.pdf> (2016). Accessed August 22 2024."},{"key":"e_1_2_16_77_1","unstructured":"Sirolimus coated tablets 0.5 1 and 2 mg oral solution 1 mg\/ml product\u2010specific bioequivalence guidance First published: May 25 2016 Last updated: May 25 2016 Reference Number: EMA\/CHMP\/315231\/2014 Legal effective date: December 1 2015<https:\/\/www.ema.europa.eu\/en\/documents\/scientific\u2010guideline\/sirolimus\u2010coated\u2010tablets\u201005\u20101\u2010and\u20102\u2010mg\u2010oral\u2010solution\u20101\u2010mgml\u2010product\u2010specific\u2010bioequivalence\u2010guidance_en.pdf> (2016). Accessed August 22 2024."},{"key":"e_1_2_16_78_1","unstructured":"Tacrolimus granules for oral suspension 0.2 and 1 mg product\u2010specific bioequivalence guidance First published: May 25 2016 Last updated: November 1 2016 Reference Number: EMA\/CHMP\/159744\/2016 Legal effective date: November 1 2016<https:\/\/www.ema.europa.eu\/en\/documents\/scientific\u2010guideline\/tacrolimus\u2010granules\u2010oral\u2010suspension\u201002\u2010and\u20101\u2010mg\u2010product\u2010specific\u2010bioequivalence\u2010guidance_en.pdf> (2016). Accessed August 22 2024."},{"key":"e_1_2_16_79_1","unstructured":"Levothyroxine tablets 12.5 mcg 25 mcg 50 mcg 75 mcg 100 mcg and 200 mcg (and additional strengths within the range) product\u2010specific bioequivalence guidance First published: December 16 2020 Reference Number: EMA\/CHMP\/176098\/2020<https:\/\/www.ema.europa.eu\/en\/documents\/scientific\u2010guideline\/levothyroxine\u2010tablets\u2010125\u2010mcg\u201025\u2010mcg\u201050\u2010mcg\u201075\u2010mcg\u2010100\u2010mcg\u2010and\u2010200\u2010mcg\u2010and\u2010additional\u2010strengths\u2010within\u2010range\u2010product\u2010specific\u2010bioequivalence\u2010guidance_en.pdf> (2020). Accessed January 5 2024."},{"key":"e_1_2_16_80_1","unstructured":"Product labeling for theophylline (anhydrous) extended\u2010release tablet 400 and 600 mg<https:\/\/dailymed.nlm.nih.gov\/dailymed\/downloadpdffile.cfm?setId=aa80b9f4\u20108a5d\u20103e14\u2010e053\u20102a95a90a8aab> (2021)."},{"key":"e_1_2_16_81_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-198506000-00005"},{"key":"e_1_2_16_82_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.48.3.227"},{"key":"e_1_2_16_83_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.140027"},{"key":"e_1_2_16_84_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt1972133349"},{"key":"e_1_2_16_85_1","first-page":"95","article-title":"Non\u2010compliance in asthmatic children: a study of theophylline levels in a pediatric emergency room population","volume":"43","author":"Sublett J.L.","year":"1979","journal-title":"Ann Allergy"},{"key":"e_1_2_16_86_1","doi-asserted-by":"publisher","DOI":"10.1159\/000233482"},{"key":"e_1_2_16_87_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201302-0388PP"},{"key":"e_1_2_16_88_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1875-9114.1983.tb04531.x"},{"key":"e_1_2_16_89_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-198303000-00009"},{"key":"e_1_2_16_90_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1976.03260440035019"},{"key":"e_1_2_16_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(86)80140-8"},{"key":"e_1_2_16_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-0644(05)82468-0"},{"key":"e_1_2_16_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(83)80682-9"},{"key":"e_1_2_16_94_1","first-page":"1164","article-title":"Evaluation of \"toxic\" serum theophylline concentrations","volume":"38","author":"Burkle W.S.","year":"1981","journal-title":"Am J Hosp Pharm"},{"key":"e_1_2_16_95_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-82-6-784"},{"key":"e_1_2_16_96_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-199001000-00013"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.3460","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T05:58:24Z","timestamp":1734501504000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.3460"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,11]]},"references-count":96,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/cpt.3460"],"URL":"https:\/\/doi.org\/10.1002\/cpt.3460","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,11]]},"assertion":[{"value":"2024-06-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}