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    Ectd Guidance

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    netelsrt1298
    This document provides an overview of post-approval CMC submissions to the FDA from an FDA perspective. It discusses the types of CMC changes that can occur over a product's lifecycle, as well as the different types of post-approval CMC submissions. It also provides guidance on submitting CMC changes in eCTD format, including using the appropriate life cycle attributes and granular file structure. Examples are given for submitting a manufacturing site change and adding a new test to drug product specifications. The presentation emphasizes including comparisons of pre- and post-change information, references, and clear identification of changes in cover letters and submissions.

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    Ectd Guidance

    Uploaded by

    netelsrt1298
    160 views37 pages
    This document provides an overview of post-approval CMC submissions to the FDA from an FDA perspective. It discusses the types of CMC changes that can occur over a product's lifecycle, as well as the different types of post-approval CMC submissions. It also provides guidance on submitting CMC changes in eCTD format, including using the appropriate life cycle attributes and granular file structure. Examples are given for submitting a manufacturing site change and adding a new test to drug product specifications. The presentation emphasizes including comparisons of pre- and post-change information, references, and clear identification of changes in cover letters and submissions.

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    This document provides an overview of post-approval CMC submissions to the FDA from an FDA perspective. It discusses the types of CMC changes that can occur over a product's lifecycle, as well as the different types of post-approval CMC submissions. It also provides guidance on submitting CMC changes in eCTD format, including using the appropriate life cycle attributes and granular file structure. Examples are given for submitting a manufacturing site change and adding a new test to drug product specifications. The presentation emphasizes including comparisons of pre- and post-change information, references, and clear identification of changes in cover letters and submissions.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    160 views37 pages

    Ectd Guidance

    Uploaded by

    netelsrt1298
    This document provides an overview of post-approval CMC submissions to the FDA from an FDA perspective. It discusses the types of CMC changes that can occur over a product's lifecycle, as well as the different types of post-approval CMC submissions. It also provides guidance on submitting CMC changes in eCTD format, including using the appropriate life cycle attributes and granular file structure. Examples are given for submitting a manufacturing site change and adding a new test to drug product specifications. The presentation emphasizes including comparisons of pre- and post-change information, references, and clear identification of changes in cover letters and submissions.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    of 37

    eCTD Post Approval CMC

    Aspects: FDA Perspective


    Hasmukh B. Patel, Ph.D.
    ONDQA, CDER, FDA
    AAPS Workshop
    Baltimore, Maryland
    March 10-11, 2009

    Presentation Outline

    Product life cycle CMC changes


    Post-Approval CMC submissions
    CMC Submissions in eCTD
    Points to consider
    Summary

    Product Life Cycle CMC


    Changes

    CMC Changes

    Manufacturing and Control sites


    Manufacturing Process
    Specifications
    Container/Closure system
    Stability Protocol
    Drug product formulation
    Labeling
    4

    Post-Approval CMC
    Submissions

    Types of Submissions

    Supplemental application
    Amendments
    Annual report
    Correspondence
    Special report

    Supplemental Applications
    For a single change (e.g. manufacturing
    site)
    Multiple changes (e.g. manufacturing
    site, manufacturing process, and inprocess controls)

    Supplemental Applications
    contd.
    Paper and electronic
    eCTD vs non-eCTD
    eCTD: Individual files for different CTD
    sections
    Non-eCTD: One document may cover many
    sections

    CMC Submissions in eCTD

    Life Cycle Attributes


    Following are post-approval activities
    related to the approved information in
    the initial application:
    Add new information
    Amend information
    Replace information
    Delete information
    10

    eCTD Submissions
    In initial submission
    Consider granularity Annex of the CTD
    Organization document (i.e., number of files)
    Consider sections likely to be supplemented
    All operation attributes set to new

    In subsequent submissions (amends & supps)


    Use the same structure
    Include only files that have changed
    Use appropriate operation attribute
    11

    eCTD Submissions contd.


    Information submitted in the following
    Modules
    Module 1
    Module 2
    Module 3

    12

    Module 1
    Cover Letters
    DMF (Letters of Authorization (LOAs)
    In 1.4.1 from your suppliers
    In 1.4.2 for who you authorize to reference
    your DMF/IND/NDA
    Not in P.3.1, S.2.1, or P.7

    13

    Module 1 contd.
    EA Categorical Exclusion
    Some submissions contain justification
    and rationale for change (which should
    not be in this module)

    14

    Module 2
    Helpful for extensive changes (e.g.,
    formulation change)
    Not needed for trivial changes (e.g.,
    secondary packaging site change)
    Do not put all data in Module 2

    15

    Example: CMC Supplement


    Adding a New Manufacturer of
    DP
    The DP site change also involves:
    Change in batch formula
    Change in manufacturing process

    16

    Example: CMC Supplement


    Adding a New Manufacturer for
    DP contd.
    Initial submission has:
    One file for manufacturer (3.2.P.3.1)
    One file for batch formula (3.2.P.3.2)
    One file for manufacturing process
    description (3.2.P.3.3)

    17

    Example: CMC Supplement


    Adding a New Manufacturer for
    DP contd.
    Initial submission has:
    One file for stability summary (3.2.P.8.1)
    One file for stability protocol and postapproval stability commitment (3.2.P.8.2)
    One file for stability data (3.2.P.8.3)
    All have new operation attribute

    18

    Example: CMC Supplement


    Adding a New Manufacturer
    for DP
    Supplement #5, sequence #015 has:
    One file for manufacturer (3.2.P.3.1) replace
    One file for batch formula (3.2.P.3.2) new
    One file for manufacturing process description
    (3.2.P.3.3) new
    One file for stability summary (3.2.P.8.1) new
    One file for stability protocol and post-approval
    stability commitment (3.2.P.8.2) new
    One file for stability data (3.2.P.8.3) new
    19

    Index.XML

    eCTD DTD version 3.2


    m3-quality
    m3-2-body-of-data
    m3-2-p-drug-product [manufacturer: AAA] [product name: YY] [dosage form:
    intravenous]

    m3-2-p-3-manufacture
    m3-2-p-3-1-manufacturers
    Manufacturer [replace]
    m3-2-p-3-2-batch-formula
    Batch Formula [new]
    m3-2-p-3-3-description-of-manufacturing-process-and-process-controls
    Description of Manufacturing Process and Process Controls [new]
    m3-2-p-8-stability
    m3-2-p-8-1-stability-summary-and-conclusion
    Stability Summary and Conclusion [new]
    m3-2-p-8-2-post-approval-stability-protocol-and-stability-commitment
    Post Approval Stability Protocol and stability Commitment [new]
    m3-2-p-8-3-stability-data
    Stability Data [new]

    20

    21

    Example: CMC Supplement


    Adding a New Test to DP Spec
    and Updating DP Assay
    method
    Adding ID test
    Change in specification
    Addition of analytical procedure

    Updating analytical procedure for DP assay


    Amending the current analytical procedure
    Validation of the updated analytical procedure
    22

    Example: CMC Supplement


    Adding a New Test to DP Spec
    and Updating DP Assay
    method

    contd.
    Initial submission has:
    One file for Specification (3.2.P.5.1)
    Several files for P.5.2 and P.5.3 (1 for each method)
    All have new operation attribute

    Supplement #1, sequence #005 has:

    One file for Specification (3.2.P.5.1) new


    One file for P.5.2 ID method new
    One file for P.5.2 updated DP assay analytical procedure new
    One file for P.5.3, validation of DP assay analytical procedure new

    23

    Leaf Titles
    eCTD DTD version 3.2
    m3-quality
    m3-2-body-of-data
    m3-2-p-drug-product [manufacturer: ABC Inc] [product name:
    XX] [dosage form: Cream]
    m3-2-p-5-control-of-drug-product
    m3-2-p-5-1-specifications
    Specifications [new]
    m3-2-p-5-2-analytical-procedures
    SSS-00100: DP Assay [new]
    MMM-00111: DP Identity [new]
    m3-2-p-5-3-validation-of-analytical-procedures
    Validation of Analytical Procedures [new]
    TTT-00200: Method Validation for the Assay of DP [new]
    MMM-00210: Validation of ID method [new]
    24

    25

    Points to Consider

    Points to Consider
    Cover letter
    Purpose of submission
    List all changes in the cover letter and
    provide link to the body of data
    Indicate which DMFs are involved
    List related supplements and ARs
    Do not include index for the submission,
    navigation is via XML backbone

    27

    Points to Consider contd.


    Pre-Change and Post Change Comparisons
    Critical for effective evaluation
    Options include:
    Word Track Changes
    Highlighting of new information
    Tabular comparisons
    Submit both files
    Pre-change file with New XML attribute if not
    already in eCTD
    Proposed changed file with Replace or Append
    attribute
    28

    Points to Consider contd.


    Provide Table of Contents (TOC) in PDF and
    link to tables, figures, data, references, and all
    supportive information within file and
    document, between documents, and where
    possible to previously approved information
    Manufacturing site(s): Identify which are
    approved and which are proposed, use an
    attribute for each site if more than one
    Provide reference to approved information if
    refered

    29

    Points to Consider contd.


    Do not spread out all materials data in
    several documents
    Dont have many small files with little
    content
    Provide link to the deleted/withdrawn
    files

    30

    eCTD DTD version 3.2


    m3-2-s-2-1-manufacturer
    3.2.S.2.1 Manufacturer [replace]
    m3-2-s-2-2-description-of-manufacturing-process-and-process-controls
    3.2.S.2.2.1 Description of the Manufacturing Process and Process
    Controls - Process 2 [new]
    3.2.S.2.2.2 Description of the Manufacturing Process and
    Process Controls Process 3 [new]
    3.2.S.2.2 Description of the Manufacturing Process and
    Process Controls [delete]

    31

    32

    Points to Consider contd.


    Global Submit document
    In some submissions, the status of the file is
    current even though the previously approved
    files has been replaced
    In the heading, no name of the drug along with
    the NDA number to identify the drug
    No way to identify the type of change proposed
    in the CMC submission quickly

    33

    34

    35

    Summary
    Submit eCTD submissions as per the Guidance
    for Industry M2 eCTD: Electronic Common
    Technical Document Specification
    Make information easily accessible through
    appropriate links for navigation and
    references
    Clearly state what has changed and what is
    approved
    36

    Thank you!!

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