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    Elemental Impurities Risk Management PDF

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    Zunjar Bagal

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    Elemental Impurities Risk Management PDF

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    138 views8 pages

    Elemental Impurities Risk Management PDF

    Uploaded by

    Zunjar Bagal

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    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    of 8

    VIEW POINT

    APPROACH TO “THE ELEMENTAL


    IMPURITIES RISK ASSESSMENT” IN
    PHARMACEUTICALS
    What are Elemental Impurities?
    The elemental impurities are the
    impurities which get introduced into
    the final drug product either directly
    through raw materials, residue by-
    products, or contact with environment,
    packaging material, manufacturing
    location, equipments, etc.
    These elemental impurities could affect
    the stability & efficacy of the finished
    product & also have hazardous effect
    on the patients and therefore they have
    to be monitored/controlled during the
    entire manufacturing process.
    The need to create a uniform approach
    to assess Elemental impurities was dual
    fold a) to minimize concerns being
    raised due to toxicological effects from
    Elemental impurities and b) to create a
    global standards in drug manufacturing.
    For centuries pharmaceutical industries
    are using manual or simple laboratory
    instruments/methods to calculate
    elemental impurities and its risk
    assessment.
    These assessment or testing process
    were not advance enough to provide
    detailed analysis of the impurities.
    However, with the advancement in
    technology, few areas like toxicology
    assessment from excipients and APIs
    have become easier and accurate
    i.e. benefiting elemental impurities
    assessment.

    External Document © 2018 Infosys Limited


    Assessment of Elemental Impurities has
    2 key benefits
    (a) Enable Global sourcing of the drugs -
    In today’s world, drug manufacturing
    is possible through global sourcing,
    where the drug substances are
    manufactured at different places
    and formulated in different location.
    If we have a global standards of
    elemental impurities assessment, then
    without further investigation the drug
    formulation could proceed, rather
    than re-testing the toxicology of the
    elements/substance
    (b) Build confidence with respect to
    standards of drug quality among
    people who are end consumers (For
    example: A particular drug bought by
    a consumer in India would be same as
    the one bought in New York).
    To address Elemental Impurities
    assessment & monitoring, there are
    guidance from International Conference
    of Harmonization (ICH) Q3D guideline:
    elemental impurities and ICH Q9: Risk
    Based Quality Control Strategy.
    This guideline applies to finished drug
    products and new drug products using
    existing drug substances. The key
    aspects of these guidelines are
    • For each dosage and route of
    administration, the Permitted Daily
    Exposure (PDE) to be established for
    the elements
    • Propose minimum levels of elemental
    impurities that is permissible based
    the Permitted Daily Exposure
    • 
    Analysis & Control of Elemental
    Impurities by risk based approach
    • Provide Element Classification to
    facilitate decision making during risk
    assessment

    External Document © 2018 Infosys Limited


    Elemental Impurity Risk
    Assessment methodology
    Elemental Impurity Risk based assessment
    is conducted by using various laboratory
    data and computing it against regulatory
    limits originated from Certificate of
    Analysis (CoA), historical data, Lab Reports,
    ICH/USP (United States Pharmacopoeia)
    limits and Product data to provide early
    insights on risk assessments to future
    batches. This process can help in
    understanding if the controls built are
    advanced enough to limit the elemental
    impurities in upcoming batches and
    documents the detailed risk assessment
    performed along with summary and
    conclusion.

    The Crux of the risk assessment approach lies in understanding where and how the impurities get into the stream

    Manufacturing Drug Substance/Active Raw


    Equipment Pharamaceutical Material/Excipient
    Ingredient

    Material of Construction Additives Colorants Preservatives


    Catalyst Intermediates
    Mantled and Dismantled Parts Bulking Agent Storage Location
    Residues Reaction additives
    New Vendor Location Filters New Vendor Logistics

    Elemental Impurities
    in Drug Product
    Gloves Shower Cap Source Storage Method Leachables and Extractables Geography New Loaction
    Personal Protective Equipment of analysis type used Materials of Construction Climate Storage
    Adhesive Lable link carboard Area Packing

    Manual Water Packaging Manufacturing


    Handling Material Location

    Fig 1: Fishbone Diagram showing sources of Elemental Impurities

    External Document © 2018 Infosys Limited


    Process steps
    The Elemental Impurities risk assessment evaluation could be performed using the below
    approach.
    Assess the elemental impurities contributed from each of the above sources to find the
    overall elemental impurities. Followed by creation of a prioritization matrix for impurities
    as per the guideline. For example: Class 1, 2, 3 and 4.
    Design an algorithm to predict probability of occurrence of impurities in the final product
    Evaluate and compare the impurities to that of established PDE (Permissible Daily Exposure)
    Lastly, implement a tool to provide holistic view on data analysis, monitoring, storage and
    visualization.

    Assess Prioritize Design Evaluate Implement

    Fig 2: Elemental Impurities Risk Assessment process steps

    External Document © 2018 Infosys Limited


    Challenges
    in Elemental
    Impurities Risk
    Assessment

    Disparate sources of Siloed data in different  No standard algorithm to


    elemental impurities – which formats - requiring manual compute the data which is
    all have to be considered? intervention common across companies

    How much data to be


     When and where to start
    collated for sufficient Unanticipated change in
    assessing the elemental
    conclusion and submission regulatory guidelines
    impurities risk?
    to regulatory body?

    External Document © 2018 Infosys Limited


    About the Authors

    How Infosys can help Pharma companies Sangita Goyal is a Consultant with Life
    Sciences Practice at Infosys Consulting.
    While drug substance manufacturing is a series of complex processes, employing
    She can be reached at
    certain scientific methods at appropriate level to plan and design efficient
    Sangita_Goyal@infosys.com
    processes will help in identifying and managing elemental impurities.
    Infosys can work hand in glove with Pharma companies to perform Risk Assessment
    of the Drug substances to meet the Regulatory standards. Dr. Nandini Diwakar is a Principal with Life
    Sciences Practice at Infosys Consulting.
    Infosys has a strong understanding of the regulation & process around Elemental
    She can be reached at
    Impurities. Infosys has the capability to help Pharma companies structure a tool
    Nandini_Diwakar@infosys.com
    with pre-defined inputs (Like Permissible Daily Exposure, Limit of Quantitation etc.),
    business rules and algorithms. This would facilitate extraction & consolidation of
    unstructured lab data from disparate sources into a structured database, help to
    Inder Neel Dua is a Senior Principal with
    query/analysis and final reporting with conclusion for regulatory submission.
    Life Sciences Practice at Infosys Consulting.
    He can be reached at
    Inder_Dua@infosys.com

    REFERENCES

    1) http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs- gen/documents/document/ucm371025.pdf

    2) http://www.nsf.org/newsroom_pdf/NSF-DBA_Elemental-Impurities_WhitePaper.pdf

    3) http://www.pharmtech.com/implementation-ich-q3d-elemental-impurities-guideline-challenges-and-opportunities

    External Document © 2018 Infosys Limited


    For more information, contact askus@infosys.com

    © 2018 Infosys Limited, Bengaluru, India. All Rights Reserved. Infosys believes the information in this document is accurate as of its publication date; such information is subject to change without notice. Infosys
    acknowledges the proprietary rights of other companies to the trademarks, product names and such other intellectual property rights mentioned in this document. Except as expressly permitted, neither this
    documentation nor any part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, printing, photocopying, recording or otherwise, without the
    prior permission of Infosys Limited and/ or any named intellectual property rights holders under this document.

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