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MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVAL MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVAL

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MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVAL - PPT Presentation

13 PROCEDURES OFFICE OF NEW DRUGS Determining the Established Pharmacologi c Class for Use in the Highlights of Prescribing Information Table of Contents PURPOSE 1 BACKGROUND ID: 84720

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MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 7400.13 Originating Office: Office of New Drugs Effective Date: 7/18/13; 7/25/18 Page 1 of 10 PROCEDURES Determining the Established Pharmacologic Class for Use in the Highlights of Prescribing Information BACKGROUND ................................................................2RESPONSIBILITIES ........................................................4PROCEDURES ..................................................................5REFERENCES ...................................................................9PURPOSE ocedures (MAPP) is to outline the process to be followed by Center for Drug Evaluation and Research (CDER) review staff when: macologic class (EPC) text phrase that will be associated with an approved indication and included under the INDICATIONS AND USAGE heading in Information (Highlights) of approved labeling Assigning clinically meaningful and scientifically valid pharmacologic concepts (i.e., mechanism of action (MOA), physiologic effect (PE), and chemical structure ) to each active moiety for use in indexing the labeling zational components of the Food and Drug Administration (FDA): Office of New Drugs (OND) pharmacology/toxicology (pharm/tox) reviewers OND Associate Director for Pharmacolpharm/tox staff Note that CS is also known as C/I (an abbreviation for chemical/ingredient), used in the U.S. Department of Veterans Affairs, Veterans Health Administration Medication Reference Terminology. MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 7400.13 Originating Office: Office of New Drugs Effective Date: 7/18/13; 7/25/18 Page 2 of 10 iate (e.g., product quality (chemistry, manufacturing, and controls (CMC)) reviewers, microbiology revipharmacology reviewers, and clinical reviewers) Office of the Commissioner (OC)/Office of the Chief Scientist, health and BACKGROUND Established Pharmacologic Class in Indications and Usage in Highlights requires that if a product is a member of an EPC, a concise statement under INDICATIONS AND USAGE in Highlights must identify the class in the following manner: “(Drug) is a (name of class) indicated for (indication(s)).” is a group of active moieties that share scientifically documented properties. Pharmacologic class is defined on the basis of any combination of three attributes of the active moiety: MOA, PE, and CS. is a pharmacologic class associated with an approved indication of an active moiety that the FDA has determined to be scientifically valid and clinically meaningful according to the following definitions: scientifically valid pharmacologic class is one thdocumented, empiric evidence showing that the active moiety’s pharmacologic class is known (not just assumed on a thclinically meaningful pharmacologic class is one pharmacologic effect enhances the abilieffects that may be associated with the active moiety or pharmacologic class. The term used to describe the EPC in INDICATIONS AND USAGLabeling for Human Prescription Drug and Biological Products — Determining EstablisHighlights of Prescribing Information We update guidances periodically. For the most recent version of a guidance, check the FDA guidance web page at https://www.fda.gov/RegulatoryInformation/Guidances/default.htm. MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 7400.13 Originating Office: Office of New Drugs Effective Date: 7/18/13; 7/25/18 Page 3 of 10 indication of an active moiety found in of one or more files that include machine-readable annotations to information that are linked to the original SPL file for the product submitted by the manufacturLinking the information in the indexing SPL files to the original SPL files enables users with computer systems upport tools and electronic prescribing systems) to rapidly search and sort product informa provides more information on this process. The staff in the Office of the Chief Scientist creates a pharmacologic class SPL index file for each active moiety that is assigned an EPC text phrase. This SPL file is thenSPL files, and maintained in program, such as Pragmatic Regulated EPC Concepts, Pharmacologic Concepts, and Identifier Codes Each EPC text phrase is associated with a term known as an EPC concept. EPC concepts use a standardized format derived from the U.S. Department of Veterans Affairs, Veterans Health Administration (VHA), Medication Reference Terminology (MED-RT). the machine-readable tag for EPC text phrase used in INDICATIONS AND USAGE in Highlights might not be the EPC concept, because the standardized language used for the EPC concept might not Each active moiety also may be assigned concepts, which are also linked to unique standardized alphanumeric MOA, PE, and CS standardized indexing concepts may or may not be related to the the active moiety for a particular scientifically valid and clinically meaningful. Even if the MOA, PE, and CS standardized they may still be useful for identifying drug interactions and permitting other safety assessments for a moiety based upon appropriateenzyme inhibition and enzyme induction. MOA, PE, and CS concepts are maintained in a standardized format as part See PRPLLR at https://elist/prpllr/. MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 7400.13 Originating Office: Office of New Drugs Effective Date: 7/18/13; 7/25/18 Page 4 of 10 RESPONSIBILITIES Pharm/tox reviewersReviewing primary and secondary pharmacology information submitted by applicants. INDICATIONS AND USAGE in Highlightlinical reviewers should be consulted for all terms, particularly to ensure that the terms are clinically meaningful and input from scribed consistently using previously nd found in the repository maintained by the OND Associate Director for Pharmand the OC/Office of the Chief Scientist.that is different r member of the pharmacologic class, when necessary. a new pharmacologic class if the sciplines and with the OND Associate Director for Pharmacology and Toxicoscientific validity and clinical meaniIdentifying the scientifically valid and clinically relevant pharmacologic MOA, PE, and CS indexing concepts for each active moiety using Reviewing and ensuring that any additional use of MOA, PE, and CS to describe moiety attributes (such as enzyme inhibition and enzyme induction), when necessary, is scientifically valid and clinically meaningful. (The pharm/tox reviewer should also consult wclinical pharmacology, product quality (CMC), and microbiology reviewers imarily from these disciplines (see This repository is currently accessed using the PRPLLR software MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 7400.13 Originating Office: Office of New Drugs Effective Date: 7/18/13; 7/25/18 Page 5 of 10 Other CDER review staff) reviewers, microbiology reviewers, clinical pharmacology reviewReviewing data relevant to the selection of a scientifically valid EPC text phrase when the data are related primarilexample, microbiology reviewers may be support of EPC text phrases for antimicrobial products. CMC reviewers may MOA, PE, and CS to describe moiety attributes is scientifically valid and clinreviewed are primarily from these disciplines. Participating in discussions with the review team regarding pharmacologic to the appropriate EPC text phrase for a particular active moiety or class of active moieties Obtaining EPC concepts and EPC concepphrases from VHA MED-RT staff EPC concepts; and MOA, PE, and CS cept codes) for all active moieties as PROCEDURES d include comments on selection of the EPC view. The selected EPC text the Pharmacology/Toxicology NDA/BLA Review and Evaluation template under MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 7400.13 Originating Office: Office of New Drugs Effective Date: 7/18/13; 7/25/18 Page 6 of 10 In some cases, a scientifically valid and clinically meaningful pharmacologic class may ty used for a specific indicatiacceptable to omit an EPC text phrase from INDICATIONS AND USAGit is generally expected that this will occur efficacy supplements that include data to support a new indication, and prior approval labeling supplements with proposed labeling that conforms to the requirements of Reviewing the Proposed Established Pharmacologic Class The pharm/tox reviewer should: Check the EPC text phrase in the applicant’s proposed labeling against the FDA EPC text phrases found in the SPL repository for each active moiety in beling if it is the same as in the the indication under review scientifically valid and clinically meaningful pharmacologic MOA, PE, and the active moiety using stCS concept hierarchies l scientifically valid and clinically meaningful MOA, PE, and CS concepts that describe such things as enzyme inhibition and enzyme induction, when necessary (see additional information New Established Pharmacologic Class If the EPC text phrase for a specificsupplement differs from that of previously approved products containing the same active moiety, the pharm/tox reviewer should: e repository for that active moiety is acceptable for the new indication; or MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 7400.13 Originating Office: Office of New Drugs Effective Date: 7/18/13; 7/25/18 Page 7 of 10 Consider if another EPC text phrase in the repository might be more appropriate. If another EPC text phrase from the repository is chosen, the pharm/tox reviewer should: Justify the selection of Notify the OND Associate Director for Pharmacology and Toxicology (or added to the active moiety in the the pharm/tox reviewer should follow the New active moiety If the new NDA/BLA is for a product containing a new active moiety, the pharm/tox reviewer should review and conssimilar active moieties. Selection of moieties in the same class is desirable. chosen, the pharm/tox reviewer should: Note the EPC text phrase in his or her review Justify its selection Review the MOA, PE, and CS concepts assigned to the active moiety in the oncepts are scientifically valid and Pharmacology and Toxicology (or designee) The pharm/tox reviewer should select — or d and clinically mand CS concepts that describe such things as enzyme inhibition and enzyme induction, when necessary. The pharm/tclinical pharmacology and clinical reviewers on the review team as necessary on these concepts. MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 7400.13 Originating Office: Office of New Drugs Effective Date: 7/18/13; 7/25/18 Page 8 of 10 phrase in the SPL repository, the pharm/tox Creating a New Established Pharmacologic Class Text PhraseWhen there is no appropriate existing EPC text phrase for an active moiety, the pharm/tox reviewer should review supportive pharmacology data and the rify that a new EPC text phrase should outlined in the guidance for industry and review staff ts — Determining Established ghlights of Prescribing InformationFor each active moiety, the pharm/tox reviase, scientifically valid and clinically meaningful MOA, PE, and CS concepts to be used for SPL indexing. The pharm/tox reviewer should consult withmacology reviewers on the review team to select additional scientifically valid and clinically meaningful MOA, PE, and CS concepts that describe such things as enzyme inhibition and enzyme induction, when used as the source of these concepts.The pharm/tox reviewer should discuss the and the MOA, PE, and CS SPL indexing concepts with other members of the is critical to ensure that the EPC text phrase and the pharmacologic indexing concepts are clinically meaningful and scientifically valid. milestone meetings or outside these meetings via email or other venues. Because pharmacology information about an active moiety may be submitted during the pplication phase of drug development, reviewers should es at this time so as to be prepared the NDA/BLA phase. The OND Associate Director for Pharmacology and Toxicology divisions. The pharm/tox reviewer should: The full list of MED-RT codes for MOA, PE, and CS can be found through the National Cancer Institute Enterprise Vocabulary Services (EVS) on the Federal Medication Terminologies web page at https://www.cancer.gov/research/resources/terminology/fmt. MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 7400.13 Originating Office: Office of New Drugs Effective Date: 7/18/13; 7/25/18 Page 9 of 10 Capture the outcome of these discussions in his or her review Note the EPC text phrase and SPL pharmacologic indexing concepts and In those rare cases where the review teamthat is scientifically valid and clinically meaningful, it is acceptable for the labeling to not include an established pharmacologic class. The pharm/tox reviewer should notify the OND Associate Director for Pharmacology and Toxicology (or designee) of the EPC text phrase and SPL pharmacologic indexing concepts assigned to the new active moiety so that the information can be added to the repository. Requesting an EPC Concept for a New Established Pharmacologic Class Director for Pharmacology and Toxicology phrase from the VHA MED-RT.Maintenance of the FDA Established Pharmacologic Class in the SPL Repository valid and clinically meaningful for a specific active moiety should be maintained ate Director for Pharmacology and Toxicology (or designee), together with th REFERENCES Final rule “Requirements on Content and Format of Labeling for Human ducts” (71 FR 3922; January 24, 2006, Use in the Highlights of Prescribing Informationmation/Guidances/default.htm EPC concepts and their NUIs are associated with each EPC text phrase and are listed for each active moiety in the FDA pharmacologic class SPL indexing file. Standardized EPC indexing concepts and NUIs are maintained by the VHA as part of its MED-RT. MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 7400.13 Originating Office: Office of New Drugs Effective Date: 7/18/13; 7/25/18 Page 10 of 10 mation/Guidances/default.htm FDA Pharmacologic Class web page ndards/StructuredProductLabeling/ucm162549.htm U.S. Department of Veterans AffairMedication Reference Terminology codes for mechanism of action, physiologic effect, and chemical structure is availaEnterprise Vocabulary Services (EVS) on the Federal Medication Terminologies webpage NCI Term Browser at h/resources/terminology/fmt Pragmatic Regulated Product Labeling Li EFFECTIVE DATE ��MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 7400.13 mation/Guidances/default.htm FDA Pharmacologic Class web page ndards/StructuredProductLabeling/ucm1 U.S. Department of Veterans AffairMedication Reference Terminology codes for mechanism of action, physiologic effect, and chemical structure is availaEnterprise Vocabulary Services (EVS) on the Federal Medication Terminologies webpage NCI Term Browser at h/resources/terminology/fmt Pragmatic Regulated Product Labeling LiEFFECTIVE DATE ��Originating Office: Office of New Drugs Effective Date: ��7/18/13��; 7/25/18 Page 10 of 10 ��MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 7400.13 Capture the outcome of these discNote the EPC text phrase and SPL pharmacologic indexing concepts and In those rare cases where the review team concludes that there is no text phrase that is scientifically valid and clinically meaningful, it is acceptable for the labeling to not include an established pharmacologic class. The pharm/tox reviewer should notify the OND Associate Director for Pharmacology and Toxicology (or designee) of the EPC text phrase and SPL pharmacologic indexing concepts assigned to the new active moiety so that the information can be added to the repository. Requesting an EPC Concept for a New Established Pharmacologic Class Director for Pharmacology and Toxicology phrase from the VHA MED-RT.Maintenance of the FDA Established Pharmacologic Class in the SPL Repository valid and clinically meaningful for a specific active moiety should be maintained ate Director for Pharmacology and Toxicology (or designee), together with thREFERENCES Final rule “Requirements on Content and Format of Labeling for Human ducts” (71 FR 3922; January 24, 2006, Use in the Highlights of Prescribing Information mation/Guidances/default.htm EPC concepts and their NUIs are associated with each EPC text phrase and are listed for each active moiety in the FDA pharmacologic class SPL indexing file. Standardized EPC indexing concepts and NUIs are maintained by the VHA as part of its MED-RT. ��Originating Office: Office of New Drugs Effective Date: ��7/18/13��; 7/25/18 Page 9 of 10 ��MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 7400.13 phrase in the SPL repository, the pharm/tox Creating a New Established Pharmacologic Class Text Phrase When there is no appropriate existing EPC text phrase for an active moiety, the pharm/tox reviewer should review supportive pharmacology data and the rify that a new EPC text phrase should outlined in the guidance for industry and review staff ts — Determining Established ghlights of Prescribing InformationFor each active moiety, the pharm/tox reviase, scientifically valid and clinically meaningful MOA, PE, and CS concepts to be used for SPL indexing. The pharm/tox reviewer should consult withmacology reviewers on the review team to select additional scientifically valid and clinically meaningful MOA, PE, and CS concepts that describe such things as enzyme inhibition and enzyme induction, when used as the source of these concepts.The pharm/tox reviewer should discuss the and the MOA, PE, and CS SPL indexing concepts with other members of the review team and division leadership. This is critical to ensure that the EPC text phrase and the pharmacologic indexing concepts are clinically meaningful and scientifically valid. milestone meetings or outside these meetings via email or other venues. Because pharmacology information about an active moiety may be submitted during the pplication phase of drug development, reviewers should begin to consider appropriate EPC text phrases at this time so as to be prepared the NDA/BLA phase. The OND Associate Director for Pharmacology and Toxicology divisions. The pharm/tox reviewer should: The full list of MED-RT codes for MOA, PE, and CS can be found through the National Cancer Institute Enterprise Vocabulary Services (EVS) on the Federal Medication Terminologies web page at https://www.cancer.gov/research/resources/terminology/fmt��Originating Office: Office of New Drugs Effective Date: ��7/18/13��; 7/25/18 Page 8 of 10 ��MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 7400.13 RESPONSIBILITIES Pharm/tox reviewersReviewing primary and secondary pharmacology information submitted by applicants. INDICATIONS AND USAGE in Highlightclinically meaningful. Clinical reviewers should be consulted for all terms, particularly to ensure that the terms are clinically meaniscribed consistently using previously selected text phrases for the EPC and found in the repository maintained by the OND Associate Director for Pharmand the OC/Office of the Chief Scientist.that is different r member of the pharmacologic class, when necessary. a new pharmacologic class if the sciplines and with the OND Associate Director for Pharmacology and Toxicoscientific validity and clinical meaniIdentifying the scientifically valid and clinically relevant pharmacologic MOA, PE, and CS indexing concepts for each active moiety using Reviewing and ensuring that any additional use of MOA, PE, and CS to describe moiety attributes (such as enzyme inhibition and enzyme induction), when necessary, is scientifically valid and clinically meaningful. (The pharm/tox reviewer should also consult wclinical pharmacology, product quality (CMC), and microbiology reviewers imarily from these disciplines (see This repository is currently accessed using ��Originating Office: Office of New Drugs Effective Date: ��7/18/13��; 7/25/18 Page 4 of 10 ��MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 7400.13 indication of an active moiety found in of one or more files that include machine-readable annotations to information that are linked to the original SPL file for the product submitted by the manufacturLinking the information in the indexing SPL files to the original SPL files enables users with computer systems upport tools and electronic prescribing systems) to rapidly search and sort product informa provides more information on this procthe Chief Scientist creates a pharmacologic class SPL index file for each active moiety that is assigned an EPC text phrase. This SPL file is thenSPL files, and maintained in program, such as Pragmatic Regulated EPC Concepts, Pharmacologic Concepts, and Identifier Codes Each EPC text phrase is associated with a term known as an EPC concept. EPC concepts use a standardized format derived from the U.S. Department of Veterans Affairs, Veterans Health Administration (VHA), Medication Reference Terminology (MED-RT). the machine-readable tag for EPC text phrase used in INDICATIONS AND USAGE in Highlights might not be the EPC concept, because the standardized language used for the EPC concept might not Each active moiety also may be assigned concepts, which are also linked to unique standardized alphanumeric MOA, PE, and CS standardized indexing concepts may or may not be related to the the active moiety for a particular scientifically valid and clinically meaningful. Even if the MOA, PE, and CS standardized they may still be useful for identifying drug interactions and permitting other safety assessments for a moiety based upon appropriateenzyme inhibition and enzyme induction. MOA, PE, and CS concepts are maintained in a standardized format as part See PRPLLR at https://elist/prpllr/. ��Originating Office: Office of New Drugs Effective Date: ��7/18/13��; 7/25/18 Page 3 of 10 ��MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 7400.13 Other CDER review staff) reviewers, microbiology reviewers, clinical pharmacology reviewReviewing data relevant to the selection of a scientifically valid EPC text phrase when the data are related primarilexample, microbiology reviewers may be support of EPC text phrases for antimicrobial products. CMC reviewers may MOA, PE, and CS to describe moiety attributes is scientifically valid and clinreviewed are primarily from these disciplines. Participating in discussions with the review team regarding pharmacologic to the appropriate EPC text phrase for a particular active moiety or class of active moieties Obtaining EPC concepts and EPC concepphrases from VHA MED-RT staff EPC concepts; and MOA, PE, and CS cept codes) for all active moieties as review cycle. The pharm/tox reviewer should include comments on selection of the EPC view. The selected EPC text the Pharmacology/Toxicology NDA/BLA Review and Evaluation template under ��Originating Office: Office of New Drugs Effective Date: ��7/18/13��; 7/25/18 Page 5 of 10 ��MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 7400.13 iate (e.g., product quality (chemistry, manufacturing, and controls (CMC)) reviewers, microbiology revipharmacology reviewers, and clinical reviewers) Office of the Commissioner (OC)/Office of the Chief Scientist, health and BACKGROUND Established Pharmacologic Class in Indications and Usage in Highlights requires that if a product is a member of an EPC, a concise statement under INDICATIONS AND USAGE in Highlights must identify the class in the following manner: “(Drug) is a (name of class) indicated for (indication(s)).” is a group of active moieties that share scientifically documented properties. Pharmacologic class is defined on the basis of any combination of three attributes of the active moiety: MOA, PE, and CS. is a pharmacologic class associated with an approved indication of an active moiety that the FDA has determined to be scientifically valid and clinically meaningful according to the following definitions: scientifically valid pharmacologic class is one thdocumented, empiric evidence showing that the active moiety’s pharmacologic class is known (not just assumed on a thclinically meaningful pharmacologic class is one pharmacologic effect enhances the abilieffects that may be associated with the active moiety or pharmacologic class. The term used to describe the EPC in INDICATIONS AND USAGLabeling for Human Prescription Drug and Biological Products — Determining EstablisHighlights of Prescribing Information We update guidances periodically. For the most recent version of a guidance, check the FDA guidance web page at https://www.fda.gov/RegulatoryInformation/Guidances/default.htm. ��Originating Office: Office of New Drugs Effective Date: ��7/18/13��; 7/25/18 Page 2 of 10 ��MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 7400.13 Consider if another EPC text phrase in the repository might be more appropriate. If another EPC text phrase from the repository is chosen, the pharm/tox reviewer should: Justify the selection of Notify the OND Associate Director for Pharmacology and Toxicology (or added to the active moiety in the the pharm/tox reviewer should follow the procedure described below for creating containing a new active moiety, the pharm/tox reviewer should review and conssimilar active moieties. Selection of moieties in the same class is desirable. chosen, the pharm/tox reviewer should: Note the EPC text phrase in his or her review Justify its selection Review the MOA, PE, and CS concepts assigned to the active moiety in the oncepts are scientifically valid and Pharmacology and Toxicology (or designee) The pharm/tox reviewer should select — or d and clinically mand CS concepts that describe such things as enzyme inhibition and enzyme induction, when necessary. The pharm/tclinical pharmacology and clinical reviewers on the review team as necessary on these concepts. ��Originating Office: Office of New Drugs Effective Date: ��7/18/13��; 7/25/18 Page 7 of 10 ��MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 7400.13 In some cases, a scientifically valid and clinically meaningful pharmacologic class may ty used for a specific indicatiacceptable to omit an EPC text phrase fromit is generally expected that this will occur efficacy supplements that include data to support a new indication, and prior approval labeling supplements with proposed labeling that conforms to the requirements of Reviewing the Proposed Established Pharmacologic Class The pharm/tox reviewer should: Check the EPC text phrase in the applicant’s proposed labeling against the FDA EPC text phrases found in the SPL repository for each active moiety in beling if it is the same as in the scientifically valid and clinically meaningful pharmacologic MOA, PE, and the active moiety using stl scientifically valid and clinically meaningful MOA, PE, and CS concepts that describe such things as enzyme inhibition and enzyme induction, when necessary (see additional information New Established Pharmacologic Class If the EPC text phrase for a specificsupplement differs from that of previously approved products containing the same active moiety, the pharm/tox reviewer should: e repository for that active moiety is acceptable for the new indication; or ��Originating Office: Office of New Drugs Effective Date: ��7/18/13��; 7/25/18 Page 6 of 10 ��MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 7400.13 Determining the Established Pharmacologic Class for Use in the Highlights of Prescribing Information RESPONSIBILITIES ........................................................4PURPOSE The purpose of this Manual of Policies and Procedures (MAPP) is to outline the process to be followed by Center for Drug Evaluation and Research (CDER) review staff when: macologic class (EPC) text phrase that will be associated with an approved indication and included under the INDICATIONS AND USAGE heading in Information (Highlights) of approved labeling Assigning clinically meaningful and scientifically valid pharmacologic concepts (i.e., mechanism of action (MOA), physiologic effect (PE), and chemical structure ) to each active moiety for use in indexing the labeling zational components of the Food and Drug Administration (FDA): Office of New Drugs (OND) pharmacology/toxicology (pharm/tox) reviewers OND Associate Director for Pharmacolpharm/tox staff Note that CS is also known as C/I (an abbreviation for chemical/ingredient), used in the U.S. Department of Veterans Affairs, Veterans Health Administration Medication Reference Terminology. ��Originating Office: Office of New Drugs Effective Date: ��7/18/13��; 7/25/18 Page 1 of 10