QbD

download QbD

of 16

  • date post

    16-Feb-2018
  • Category

    Documents

  • view

    227
  • download

    1

Embed Size (px)

Transcript of QbD

  • 7/23/2019 QbD Overview.pdf

    1/16

    The information contained in this presentation is proprietary to Colorcon and may not be used or disseminated inappropriately.

    Quality by Design (QbD)

  • 7/23/2019 QbD Overview.pdf

    2/16

    The information contained in this presentation is proprietary to Colorcon and may not be used or disseminated inappropriately.

    Why QbD?

    Higher level of assurance of product quality

    Cost saving and efficiency for industry and regulators

    Increase efficiency of manufacturing process and reduce manufacturing cost

    and product rejects

    Minimize/eliminate potential compliance actions, costly penalties & recalls

    Enhance opportunities for first cycle approval

    Streamline post approval manufacturing changes and regulatory processes

  • 7/23/2019 QbD Overview.pdf

    3/16

    The information contained in this presentation is proprietary to Colorcon and may not be used or disseminated inappropriately.

    FDA View on QbD

    Quality by Design is: Scientific, risk-based, holistic and proactive approach to

    pharmaceutical development

    Deliberate design effort from product conception through

    commercialization

    Full understanding of how product attributes and process relate to

    product performance

    QbD informat ion and conc lus ions shou ld be shared wi th FDA,required start ing in 2013

  • 7/23/2019 QbD Overview.pdf

    4/16

    The information contained in this presentation is proprietary to Colorcon and may not be used or disseminated inappropriately.

    QbD System

    Define desiredproduct performance

    upfront;

    identify product CQAs

    Design formulation andprocess to meet

    product CQAs

    Understand impact ofmaterial attributes andprocess parameters on

    product CQAs

    Identify and controlsources of variability

    in material andprocess

    Continually monitorand update

    process to assureconsistent quality

    Risk assessment and risk control

    Product & process design and development

  • 7/23/2019 QbD Overview.pdf

    5/16

    The information contained in this presentation is proprietary to Colorcon and may not be used or disseminated inappropriately.

    Approaches to Pharmaceutical Development

    Aspects Traditional QbD

    Pharmaceuticaldevelopment

    Empirical; typically univariateexperiments

    Systematic; multivariate experiments

    Manufacturingprocess

    Fixed; validation on 3 initial full-scalebatches; focus on reproducibility

    Adjustable within design space;continuous verification within designspace; focus on control strategy androbustness

    Process control In-process testing for go/no-go; offlineanalysis w/ slow response

    All critical process variables understood

    Productspecification

    Primary means of quality control;based on batch data

    Part of the overall quality controlstrategy; based on desired productperformance

    Control strategyMainly by intermediate and endproduct testing

    Risk-based; controls shifted upstream;real-time release

    Lifecyclemanagement

    Reactive to problems & OOS; post-approval changes needed

    Continual improvement enabled withindesign space

  • 7/23/2019 QbD Overview.pdf

    6/16

    The information contained in this presentation is proprietary to Colorcon and may not be used or disseminated inappropriately.

    Designing a Robust Process

    Problemsdetected after they occur,

    through

    product testing andinspection

    Reproducible process

    within

    narrow operatingranges

    Robust & reproducible

    process

    Low High

    Low

    High

    PROCESS UNDERSTANDING

    PROCESS

    CONTROL

    High potential

    for failures

  • 7/23/2019 QbD Overview.pdf

    7/16

    The information contained in this presentation is proprietary to Colorcon and may not be used or disseminated inappropriately.

    Quality by DesignThe Desired State

    Product quality and performance achieved and assured by design ofeffective and efficient manufacturing processes

    Product specifications based on mechanistic understanding of howformulation and process factors impact product performance

    An ability to affect continuous improvement and continuous real timeassurance of quality

  • 7/23/2019 QbD Overview.pdf

    8/16

    The information contained in this presentation is proprietary to Colorcon and may not be used or disseminated inappropriately.

    Quality by DesignThe Way Forward

    Identify and control all sources of

    variability

    Raw materials

    Process

    Environmental

    Manage variability through the

    process

    Uncertainty the inability to determine or

    the ambiguity in the true state of a system

    caused by a combination of variability and

    incomplete knowledge (ICH Q9)

    Reduce UNCERTAINTY Control VARIABILITY

    Mitigate risk

    Knowledge transfer to manufacturing and regulatory bodies

  • 7/23/2019 QbD Overview.pdf

    9/16

    The information contained in this presentation is proprietary to Colorcon and may not be used or disseminated inappropriately.

    Quality Risk Assessment (QRA)

    Risk scores based on probability, severity, and detectability Risk Prioritization Matrix

    Quality Function Deployment

    Fish bone or Ishikawa diagram

    Pareto Chart

  • 7/23/2019 QbD Overview.pdf

    10/16

    The information contained in this presentation is proprietary to Colorcon and may not be used or disseminated inappropriately.

    Risk Prioritization Matrix

    Process and Formulation Inputs

    QUALITYATTRIBUTES

    WEIGHTED

    AVERAGE

    HPMCK100CR

    CONCENTRAT

    ION

    BLENDTIME

    LUBETIME

    APIPARTICLE

    SIZE

    PRE-

    COMPRESSION

    FORCE

    COMPRESSING

    FORCE

    MACHINESPE

    ED

    FEEDERSPE

    ED

    POROSITYO

    F

    RIBBON/ROLL

    GAP

    EXCIPIENT

    PARTICLESIZE

    PSDOFINTR

    A-

    GRANULAR

    BLEND

    REGULATOR

    Y

    MANUFACTUR

    ING

    DISSOLUTION 10 10 1 1 1 1 1 1 1 1 1 1 10 3

    ASSAY/

    POTENCY9 3 1 5 5 1 1 1 1 7 1 1 10 1

    UNIFORMITY 7 1 7 1 5 1 1 5 7 7 3 5 5 1

    HARDNESS 10 5 5 10 5 7 10 7 7 10 5 5 10 10

    THICKNESS 5 3 1 1 1 7 10 3 1 1 1 1 1 5

    FLOW 4 7 5 1 3 1 1 3 7 5 5 7 3 1

    APPEARANCE 4 5 1 3 3 3 5 3 5 5 5 5 1 1

    STABILITY 2 1 1 1 1 1 1 1 1 1 1 1 3 1

    YIELD 7 1 1 1 1 1 1 10 3 3 1 3 7 10

    TOTALS 256 156 192 178 156 209 235 200 236 144 180

    PERCENTIMPORTANCE

    11.95 7.28 8.96 8.31 7.28 9.76 10.97 9.34 11.01 6.72 8.40

  • 7/23/2019 QbD Overview.pdf

    11/16

    The information contained in this presentation is proprietary to Colorcon and may not be used or disseminated inappropriately.

    Tablet Hardness

    Basic risk facilitation methods

    Cause EffectDiagram

    for Tablet

    Hardness

    Compression

    Roller Compaction

    Raw MaterialBlending

    EnvironmentalMaterial

    Transfer

    Hardness of Tablet

    (Friability)

    Pre & Post CompressionPress speed

    Feeder speedMaterial addition

    Feed frame settingFill Weight

    Cam selectionTooling

    Roll GapRoll force

    Porosity (den)PSD

    Ribbon strength

    APIHPMC

    TALCMg. Stea

    Temp.Humidity

    Blend time

    Blend rpm

    Order of ddn.Fill Vol.

    Discharge rateSurface

    DischargeStorage

    MoistureTransport

  • 7/23/2019 QbD Overview.pdf

    12/16

    The information contained in this presentation is proprietary to Colorcon and may not be used or disseminated inappropriately.

    Pareto Chart: Relative Importance of Inputs

    0.00%

    2.00%

    4.00%

    6.00%

    8.00%

    10.00%

    12.00%

    14.00%

    HPMC

    K100CR

    POROSITY

    PRESSSPEED

    COMPRESSIO

    N

    FORCE

    FEEDER

    SPEE

    D

    LUBETIME

    PSD

    OFINTRA-

    GRANULAR

    BLEND

    APIPARTICLESIZ

    E

    BLEND

    TIME

    PRE-COMPFORC

    E

    EXCIPIENT

    PARTICLESIZE

  • 7/23/2019 QbD Overview.pdf

    13/16

    The information contained in this presentation is proprietary to Colorcon and may not be used or disseminated inappropriately.

    Control/Design Space Critical Process Parameters

    Critical Process Parameters (CPP) identified using a risk analysis investigatedextensively using a DOE.

    Design Space

    Established on the basis of the DOE and experience duringmanufacture of clinical/registration batches

    In certain cases where response of critical quality attributestudied/investigated was insignificant, extrapolation was used toexpand/establish design space

    Control Space

    Subset of design space established on the basis of process

    capability, prior knowledge Intent is to stay within the control space during commercial manufacturing

  • 7/23/2019 QbD Overview.pdf

    14/16

    The information contained in this presentation is proprietary to Colorcon and may not be used or disseminated inappropriately.

    Control/Design Space Non-Critical Process Parameters

    Non-Critical Process Parameters those identified as low risk which

    lead to low probability of product failure

    Design Space

    Established on the basis of range studies (in some cases

    DOEs) and manufacturing experience at various scales

    Control Space

    Subset of design space established on the basis of process

    capability, prior knowledge

    Intent is to stay within the control space during commercial

    manufacturing

  • 7/23/2019 QbD Over