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    Sample Size Selection-USP - FDA - ASTM

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    1) FDA, USP, and ASTM each play a role in setting standards related to pharmaceutical quality and testing. 2) FDA establishes regulatory standards for product quality control, design, and manufacturing. USP sets market standards and standard testing methods. ASTM and other consensus standards organizations develop industry standards and standard methods. 3) Sampling plans used to ensure batch quality must comply with cGMP regulations and be adequate to assure product meets specifications with an acceptable level of confidence.

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    Sample Size Selection-USP - FDA - ASTM

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    1) FDA, USP, and ASTM each play a role in setting standards related to pharmaceutical quality and testing. 2) FDA establishes regulatory standards for product quality control, design, and manufacturing. USP sets market standards and standard testing methods. ASTM and other consensus standards organizations develop industry standards and standard methods. 3) Sampling plans used to ensure batch quality must comply with cGMP regulations and be adequate to assure product meets specifications with an acceptable level of confidence.

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    Sample Size Selection-USP - FDA - ASTM

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    1) FDA, USP, and ASTM each play a role in setting standards related to pharmaceutical quality and testing. 2) FDA establishes regulatory standards for product quality control, design, and manufacturing. USP sets market standards and standard testing methods. ASTM and other consensus standards organizations develop industry standards and standard methods. 3) Sampling plans used to ensure batch quality must comply with cGMP regulations and be adequate to assure product meets specifications with an acceptable level of confidence.

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    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    610 views27 pages

    Sample Size Selection-USP - FDA - ASTM

    Uploaded by

    vg_vvg
    1) FDA, USP, and ASTM each play a role in setting standards related to pharmaceutical quality and testing. 2) FDA establishes regulatory standards for product quality control, design, and manufacturing. USP sets market standards and standard testing methods. ASTM and other consensus standards organizations develop industry standards and standard methods. 3) Sampling plans used to ensure batch quality must comply with cGMP regulations and be adequate to assure product meets specifications with an acceptable level of confidence.

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    At a glance
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    The key takeaways are that FDA, USP and ASTM each play a role in setting standards for product quality. FDA focuses on regulatory standards and product/process design and quality control. USP sets market and compendial standards. ASTM and other consensus standards organizations set industry standards and standard methods.

    The two types of quality discussed are product design/specifications and ensuring low risk of failing to meet clinical attributes.

    Regulators set and enforce regulatory standards. USP sets market standards and standard methods. ASTM and other consensus standards organizations set industry standards and standard methods.

    Sample Size Selection

    Role of Regulators, USP, and ASTM

    Keith O. Webber, Ph.D.


    Deputy Director
    Office of Pharmaceutical Science
    Acting Director
    Office of Generic Drugs
    CDER, FDA

    Why Test?
    Assessment of Quality
    Verification of Quality
    End-Product Testing
    Rejection of out-of-spec lots

    In-process Testing
    In lieu of end-product testing
    As part of in-process QC system
    2

    Two Types of Quality


    The suitability of either a drug substance
    or drug product for its intended use.
    ICH Q6A Specifications Guideline

    The state of having an acceptably low risk


    of failing to achieve the desired clinical
    attributes.
    J. Woodcock, M.D.
    Amer. Pharm. Rev. (NovemberDecember 2004)
    3

    Desired State
    Product specifications based on
    mechanistic understanding of how
    formulation and process factors impact
    product performance
    Product quality and performance achieved
    and assured by design of effective and
    efficient manufacturing processes
    4

    Two Types of Quality


    Product design
    Tablet Coating Design

    http://www.medscape.org/viewarticle/540104_4

    From: Pharmaceutical Formulation & Quality


    TABLET COATINGS: Tune into Terahertz
    L Ho, KC Gordon, T Rades, & P Taday

    Specifications define the design.


    5

    Batch/Lot Quality
    Within-Lot Distribution

    Lower Spec Limit

    Upper Spec Limit

    Attribute
    6

    Batch/Lot Quality
    Within-Lot Distribution

    Lower Spec Limit

    Upper Spec Limit

    Attribute
    7

    Numbers of tablets out-of-spec


    Spec range = 75-125%
    batch size = 1,000,000 tablets

    Sigma

    Mean
    95%
    100%

    105%

    6%
    7%
    7.8%

    430
    2150
    5232

    430
    2150
    5232

    30
    360
    1350

    8
    Dr. Janet W oodcock, April 9, 2002

    Sample Size and Confidence


    Calculating Sample Size (ASTM: E122 - 09)
    Demonstrating Confidence in Complying with
    an Acceptance Procedure (ASTM: E270910)
    Confidence in Attribute Sampling (ASTM
    E2334-09
    9

    FDA , USP, ASTM


    Each is involved in setting standards
    associated with product quality.

    10

    Regulators Role
    Reviewer, Inspector, Compliance Officer
    Set and enforce regulatory standards for:
    Product quality (lot release & shelf life)
    Quality control
    Manufacturing control

    11

    Reviewers Role
    Ensure that product design is consistent
    with products performance requirements
    Ensure that process design is capable of
    producing product that meets
    specifications
    Assess the process controls and the level
    of confidence that units in a batch will
    meet specifications
    12

    Inspectors Role
    Assess the ability of the manufacturer to
    appropriately manufacture the product in
    accordance with cGMPs and the
    parameters in the marketing application.
    Maintaining control
    Routine sampling

    Adequately responding to and investigating


    deviations
    Enhanced sampling adequate for intended
    purpose?
    13

    Compliance Officers Role


    Work with the Reviewer to ensure that the
    sampling plans to be approved are compliant
    with cGMPs
    Work closely and coordinate with ORA
    Headquarters and Field Units on the review of
    inspectional observations (483) and
    Establishment Inspection Report (EIR) to
    determine what (if any) regulatory action is
    necessary to achieve compliance with cGMPs.
    14

    Regulation on
    Selection of Units
    21 CFR 211.165(d)
    adequate to assure that batches of drug
    products meet each appropriate specification
    and appropriate statistical quality control
    criteria as a condition for their approval and
    release

    15

    USPs Role
    Standards Mandated by Law
    USP/NF referenced in 21 U.S.C. 351

    Market Standards

    16

    Adulteration & the USP


    A drug may be considered adulterated :
    If it purports to be or is represented as a drug the name of
    which is recognized in an official compendium, and its
    strength differs from, or its quality or purity falls below, the
    standard set forth in such compendium. Such determination
    as to strength, quality, or purity shall be made in accordance
    with the tests or methods of assay set forth in such
    compendium,
    FDCA 501(b)
    17

    USP General Notices


    34th Revision
    At times, compendial standards take on the character of
    statistical procedures, with multiple units involved
    The similarity to statistical procedures may seem to
    suggest an intent to make inference to some larger
    group of units, but in all cases, statements about
    whether the compendial standard is met apply only to
    the units tested
    Repeats, replicates, statistical rejection of outliers, or
    extrapolations of results to larger populations, as well as
    necessity and appropriate frequency of batch testing, are
    neither specified nor proscribed by the compendia.
    18

    USP General Notices


    34th Revision
    The manufacturers specifications, and good
    manufacturing practices generally (including,
    e.g., Quality by Design initiatives) are developed
    and followed to ensure that the article will
    comply with compendial standards until its
    expiration date
    Frequency of testing and sampling are left to
    the preferences or direction of those performing
    compliance testing, and other users of USP-NF,
    including manufacturers, buyers, or regulatory
    authorities.
    19

    Consensus Standards Orgs.


    (e.g., ASTM)
    Congress: National Technology Transfer
    and Advancement Act (NTTAA); 1995
    Office of Management and Budget (OMB):
    Circular A-119; 1998 (original in 1993)
    http://standards.gov/standards_gov/index.
    20
    cfm

    Consensus Standards Orgs.


    (e.g., ASTM)
    OMB Circular A-119
    this Circular directs agencies to use
    voluntary consensus standards in lieu of
    government-unique standards except where
    inconsistent with law or otherwise impractical.

    21

    Use voluntary consensus


    standards
    To determine whether established
    regulatory limits or targets have been met
    Test methods
    Sampling procedures
    Protocols
    22

    ASTM Standards for


    Sampling / Statistics
    E105 - 10:

    Probability Sampling Of Materials

    E122 - 09:

    Calculating Sample Size to Estimate, With Specified


    Precision, the Average for a Characteristic of a Lot or
    Process

    E141 - 10:

    Acceptance of Evidence Based on the Results of


    Probability Sampling

    E178 - 08:

    Dealing With Outlying Observations

    E2709 - 10: Demonstrating Confidence in Complying with Acceptance


    Procedures
    E2587 - 10 : Statistical Process Control
    E2334 09: Confidence in Attribute Sampling
    E2281 10: Process Capability
    23

    CSOs and FDAs authority


    This policy does not preempt or restrict
    agencies authorities and responsibilities
    to make regulatory decisions authorized
    by statute.
    These include
    Determining the level of acceptable risk
    Setting the level of protection
    Balancing risk, cost and availability of
    technology in establishing regulatory
    standards.

    24

    FDA , USP, ASTM


    Each is involved in setting standards for
    product quality.
    FDA Regulatory standards
    Product design & quality control

    USP Market stds. & standard methods


    CSOs (e.g., ASTM) Industry standards
    Standard Methods
    25

    FDA, USP, ASTM


    Regulatory Standards

    FDA

    USP
    Market Standards
    & Standard Methods

    CSOs*
    Industry
    Standards
    *e.g., ASTM

    26

    Acknowledgements

    Alex Viehmann
    Jon Clark
    Ali Afnan
    Steven Lynn
    Helen Winkle

    27

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