INTRODUCTION%20TO%20ICH%20Q8%20 - PowerPoint PPT Presentation

View by Category
About This Presentation
Title:

INTRODUCTION%20TO%20ICH%20Q8%20

Description:

Q8 Annexure ('Draft stage') - Provides further clarification to Q8 concepts ... It should never be used as a 'hobby horse' / preconceived idea ... – PowerPoint PPT presentation

Number of Views:435
Avg rating:3.0/5.0
Slides: 52
Provided by: BABU2
Learn more at: http://www.ipapharma.org
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: INTRODUCTION%20TO%20ICH%20Q8%20


1
INTRODUCTION TO ICH Q8 Q9 GUIDELINES
  • K. S. BABU
  • Head - Corporate Regulatory Affairs
  • Watson Pharma., India
  • November 29, 2007

2
FOREWORD
  • EMPHASIS
  • Interpretation of guidance documents
  • Regulatory relevance applications
  • Bonus Q10 guideline, due to its relevance

3
WHAT ARE THESE GUIDELINES ABOUT?
  • Q8 - Pharmaceutical Development
    (Implemented)
  • - Contents of 3.2.P.2 Section of Module 3, CTD
  • Q8 Annexure (Draft stage)
  • - Provides further clarification to Q8 concepts
  • - Links QbD PAT (FDA), QRM (EU),
    FEMA
  • Q9 - Quality Risk Management (Implemented)
  • Q10 - Pharmaceutical Quality System (Draft
    stage)

4
REGULATORY STATUS OF ICH Q 8
  • Reached Step 5 Regulatory Implementation
  • EU
  • Transmission to CHMP and to Interested Parties in
    December 2004. Issued as EMEA/CHMP/167068/2004-ICH
    . Deadline for comments June 2005. Final
    approval by CHMP November 2005. Date for coming
    into operation May 2006.
  • MHLW
  • Adopted on September 1, 2006, PFSB/ELD
    Notification N 0901001
  • FDA
  • Published in the Federal Register, Vol. 71, No
    98, May 22, 2006

5
REGULATORY STATUS OF ICH Q 8 - Annexure
  • Reached Step 3 in Nov. 2007
  • Regulatory Consultation Discussion
  • Draft Guideline
  • EU / MHLW / FDA TO BE NOTIFIED

6
REGULATORY STATUS OF ICH Q 9
  • Reached Step 5 Regulatory Implementation
  • EU
  • Published on the EMEA website
  • MHLW
  • Adopted on September 1, 2006, PFSB/ELD
    Notification n 0901004
  • FDA
  • Published in the Federal Register, Vol. 71, No
    106, pages 32105-32106, June 2, 2006

7
REGULATORY STATUS OF ICH Q 10
  • Reached Step 3 in May 2007
  • - Regulatory Consultation Discussion
  • - Draft Guideline
  • EU
  • Transmission to CHMP and to Interested Parties
    May 2007. Issued as EMEA/CHMP/ICH/214732/2007.
    Deadline for comments November 2007.
  • MHLW
  • Released for consultation 13th July 2007,
    PFSB/ELD, deadline for comments 1st October 2007
  • FDA
  • Published in the Federal Register July 13, 2007,
    Volume 72, No. 134, pages 38604-38605. Deadline
    for comments October 11, 2007.

8
BRIEF NOTE ON ICH Q10 P.Q.S.
  • Based on ISO concepts
  • Includes applicable GMP regulations
  • Compliments ICH Q8 and ICH Q9
  • Acts as a model for a pharmaceutical quality
    system that can be implemented throughout the
    different stages of a product lifecycle.
  • Content is currently specified by regional GMP
    requirements
  • Not intended to create any new expectations
    beyond current regulatory requirements
  • Consequently, the content of ICH Q10 that is
    additional to current GMP requirements is optional

9
Q8 OVERVIEW
  • Talks about Pharmaceutical Dev. section in
    regulatory submissions
  • Suggested Contents for 3.2.P.2 of CTD Quality
    Module 3
  • 3.2.P.2.1 Components of drug product (drug
    substance/ excipients)
  • 3.2.P.2.2 Formulation Dev.
  • 3.2.P.2.3 Manufacturing Process Development
  • 3.2.P.2.4 Container Closure System
  • 3.2.P.2.5 Microbiological Attributes
  • 3.2.P.2.6 Compatibility
  • There is much more than
  • meeting the filing requirements or CTD check-list

10
Q8 OVERVIEW (contd.)
  • Greater understanding of the product / process
    variables
  • Science- and risk-based submissions
  • Wider regulatory flexibility
  • Q8 Annexure Q R M (ICH Q9)

11
Q8 Related EU Directives and Guidelines
  • 2003/63/EC, Annex I, 3.2.2.2 Pharmaceutical
    Development
  • CPMP/QWP/155/96 Guideline on Development
    Pharmaceutics
  • NTA Volume 2B - Common Technical Document
  • Note for guidance on development pharmaceutics
    (EMEA/CHMP/167068/2004)
  • Link to EU Directives
  • http//ec.europa.eu/enterprise/pharmaceuticals/eud
    ralex/homev1.htm

12
Q8 Objectives of Pharmaceutical Dev. Section
  • UNDERSTANDING Provide a comprehensive
    understating of the product and manufacturing
    process for reviewers and inspectors
  • EVIDENCE Establish evidence that the dosage
    form, the formulation, manufacturing process,
    container closure system, microbiological
    attributes and usage instructions are appropriate
    for the intended use
  • ASSURANCE Provide scientific discussion to
    support that
  • the design / process will consistently deliver a
    quality product
  • SYSTEMATIC ASSESSMENT
  • Testing during developmental stage Extensive
    Different from routine
  • Critical parameters of the formulation and
    process which can influence batch
    reproducibility, medicinal product performance
    and medicinal product quality shall be identified
    and described.

13
Q8 IMPORTANT CONSIDERATIONS
  • 3.2.P.2.1.1 Drug Substance
  • Key physicochemical characteristics of the drug
    substance (e.g. solubility, water content,
    particle size distribution), which are variable
    and critical for the quality of the product and
    which can influence the performance of the drug
    product
  • Compatibility of drug substance with the
    excipients
  • For combination products, the compatibility of
    the drug substances with each other
  • Polymorphism issues

14
Q8 IMPORTANT CONSIDERATIONS (contd.)
  • 3.2.P.2.1.2 Excipients
  • Choice of excipients (in particular relative to
    their respective functions) their concentration
    (with justification)
  • Their characteristics that may influence the drug
    product performance
  • Compatibility of excipients with other
    excipients, where relevant
  • Justification for their inclusion, in some cases
    (e.g. preservatives, anti-oxidants) accompanied
    by experimental data
  • Safety of the excipients, where relevant

15
Q8 IMPORTANT CONSIDERATIONS (contd.)
  • 3.2.P.2.2.1 Formulation Development
  • Differences between clinical formulations and
    current formulation
  • Summary describing the development of the
    formulation including identification of critical
    attributes to the quality of the drug product
  • The choice of drug product components (drug
    substance, excipients, container closure system
    etc.,) and the manufacturing process
  • Results of comparative in vitro studies
    (dissolution) and in vivo studies
    (bio-equivalence), when appropriate
  • Any special design features of the drug product
    (tablet score line,over fill etc.,)

16
Q8 IMPORTANT CONSIDERATIONS (contd.)
  • 3.2.P.2.2.2 Overages
  • Use of an overage of a drug substance to
    compensate for degradation during manufacture or
    a products shelf life, or to extend shelf life,
    is discouraged
  • A justification of any overage on grounds of
    safety and efficacy
  • Information on amount of overage, reason for the
    overage and the justification for the amount of
    overage.

17
Q8 IMPORTANT CONSIDERATIONS (contd.)
  • 3.2.P.2.2.3 Physicochemical and Biological
    parameters
  • The physicochemical and biological properties
    relevant to the safety, performance or
    manufacturability of the drug product should be
    identified and discussed
  • The selection of dissolution testing should be
    discussed.

18
Q8 IMPORTANT CONSIDERATIONS (contd.)
  • 3.2.P.2.3 Manufacturing Process Development
  • Basis for process improvement, process
    validation, continuous process verification and
    process control requirements.
  • The selection, the control, and any improvement
    of the manufacturing process.
  • Appropriateness of the equipment used for the
    intended product.
  • For the sterile products, appropriate method of
    sterilization and the primary packaging material
    selection should be discussed.

19
Q8 IMPORTANT CONSIDERATIONS (contd.)
  • 3.2.P.2.3 Manufacturing Process Development
    (contd.)
  • Significant difference between the manufacturing
    process of pivotal batches and intended
    commercial batches.
  • If differences are there, the influence of the
    difference on product performance,
    manufacturability and quality to be discussed.
  • Experiments of laboratory scale batches should be
    described.
  • Information from scaling up from laboratory
    through pilot to production scale to justify that
    scale-up can be achieved without a consequent
    loss in quality.

20
Q8 IMPORTANT CONSIDERATIONS (contd.)
  • 3.2.P.2.4 Container Closure System
  • Discussion on the suitability of the container
    closure system used for storage, transportation
    and use of the product
  • This discussion should consider
  • choice of the materials for primary packaging
  • protection from moisture and light
  • compatibility of the materials with the dosage
    form
  • performance of the dose delivery from the device
    if dosing device is used
  • Food grade certification

21
Q8 IMPORTANT CONSIDERATIONS (contd.)
  • 3.2.P.2.5 Microbiological Attributes
  • Where appropriate the microbiological attributes
    of the dosage form should be addressed (according
    to Ph.Eur.). The discussion should include for
    example
  • The rationale for performing or not performing
    microbial limits testing for non-sterile
    products.
  • The selection and effectiveness of preservative
    systems in products containing antimicrobial
    preservatives.
  • For sterile products, the integrity of the
    container closure system as it relates to
    preventing microbial contamination.
  • The lowest concentration of antimicrobial
    preservative should be demonstrated to be
    effective in controlling microorganisms.

22
Q8 IMPORTANT CONSIDERATIONS (contd.)
  • 3.2.P.2.6 Compatibility
  • The compatibility of the drug product with
    reconstitution diluent(s) should be addressed to
    provide appropriate labelling information.
  • This information should cover the recommended
    in-use shelf life at the recommended storage
    temperature.

23
Q8 OVERVIEW (contd.)
  • Greater understanding of the product / process
    variables
  • Science- and risk-based submissions
  • Wider regulatory flexibility
  • Q8 Annexure Q R M (ICH Q9)

24
Specific Cases
  • Use of one lot of API for Exhibit batches PSD
    Profile Optimization
  • Impact of age of API used in Exhibit batches
  • Blend time optimization
  • Switching to alternate sources for Excipients
    (E.g., Mg.Stearate Animal grade to Veg. grade)

25
Focus of Q8 Annexure
  • Define Target Product Profile
  • Identify CQAs Critical Quality Attributes of
    Product
  • Determine QAs of inputs materials/parameters
    etc.
  • Select appropriate process
  • Determine functional relationships between
    material attributes process parameters to
    Product CQAs
  • Identify a control strategy
  • Propose a design space
  • Define and describe design space in regulatory
    submission

26
Focus of Q8 Annexure (contd.)
  • Defining DESIGN SPACE Options -
  • Ranges of input variables or parameters
  • Analysis of historical data can be basis
  • Scaling factors
  • Multivariate operations
  • Operation within the design space results in a
    product that meets the defined quality attributes
  • Periodic reassessment throughout life-cycle

27
ICH Q 9 (QRM) as part of development
  • To design a quality product and its manufacturing
    process
  • to consistently deliver the intended performance
    of the product
  • To enhance knowledge of product performance over
    a wide range of
  • material attributes (e.g. particle size
    distribution, moisture content, flow properties)
  • processing options
  • process parameters

28
QRM as part of development (contd.)
  • To assess the critical attributes of
  • Raw materials
  • Solvents
  • Active Pharmaceutical Ingredient (API)
  • Starting materials
  • Excipients
  • Packaging materials
  • To establish appropriate specifications, identify
    critical process parameters and establish
    manufacturing controls

29
QRM as part of development (contd.)
  • To decrease variability of quality attributes
  • reduce product and material defects
  • reduce manufacturing defects
  • To assess the need for additional studies (e.g.,
    bioequivalence, stability) relating to scale up
    and technology transfer
  • To make use of the design space concept
    (annexure to ICH Q8)

30
Q9 QUALITY RISK MANAGEMENT
  • What is risk?
  • Combination of the probability of occurrence of
    harm, and the severity of that harm.
  • Fact No process is risk-free

31
MANAGING RISKS IN A COMPANY
ICH Q9
32
EMEA NOTE ON Q9
33
Q9 Dangers from Absence of Risk Management
  • Pharmaceutical products may not be available to
    patients when needed, e.g. when a product is
    recalled from a market or where different risk
    decisions contribute to inefficient manufacturing
    processes and consequent delays
  • May increase the potential for the release of
    unacceptable product to the market
  • Delays may occur during implementation of changes
    and improvements to processes
  • Safe and effective drugs may be discarded or
    recalled from the market
  • Manufacturers may be reluctant to implement new
    technologies or continuous improvements to
    products or processes
  • Scarce resources may not be optimally allocated
  • Lack of appropriate date to evaluate risk most
    effectively

34
Q9 Purpose Objectives
  • No national guidance documents in this area in
    any region
  • No common understanding of terms, principles and
    application of risk management
  • Development of a harmonised pharmaceutical
    quality system applicable across the life cycle
    of the product emphasising an integrated approach
    to risk management and science
  • Deriving common terminology, including a
    definition of quality, risk, risk management etc
  • Defining the principles for how risk management
    can be effectively applied and consistently
    integrated into decisions regarding product
    quality
  • Rationalization Operationalization of the
    integration of risk management into the decision
    making process

35
Q9 Purpose Objectives (contd.)
  • Defining criteria on how to apply the risk
    management process
  • Identification of circumstances, if any, when
    applying risk management principles is not
    feasible or appropriate
  • Defining what principles of risk management apply
    to industry, regulators or both across the
    life-cycle of the product
  • Establish - how, what when information is
    exchanged between within industry, to the
    regulators, and to both, throughout the product
    life cycle
  • Emphasize synergies with the pharmaceutical
    development project
  • Defining roles and responsibilities of regulators
    and industry
  • Discuss how risk can be incorporated into
    resource allocation decisions

36
Q9 Benefits of Quality Risk Management Approach
  • Enhancement of patient confidence worldwide in
    decision making on the quality of pharmaceuticals
  • Promotion of more effective use of regulatory and
    industry resources
  • Establishment of a systematic, well-informed and
    thorough method of decision making which leads to
    greater transparency and predictability
  • Increased knowledge of exposure to risk
  • A greater assurance to regulators of a companys
    ability to deal with potential risks
  • Fostering continuous improvement and quality by
    design generally leading to enhanced product
    quality
  • Enables right decision making

37
Quality Risk Management Process
38
Risk Assessment
  • 3 Stages
  • Risk identification what are the hazards?
  • Risk analysis risk associated with identified
    hazards
  • Risk evaluation comparison of identified and
    analyzed risk against a given risk criteria
  • 3 fundamental questions
  • What might go wrong?
  • What is the likelihood it will go wrong?
    Probability
  • What are the consequences? Severity

39
Risk Control
  • Decision making
  • Risk reduction? Or
  • Risk acceptance?
  • Basis for Judgment
  • Is the risk above an acceptable level?
  • What can done to reduce or eliminate risks?
  • What is the appropriate balance among benefits,
    risks and resources?
  • Are new risks introduced as a result of the
    identified risks being controlled?

40
Risk Management methodology
  • Recognized risk management tools
  • Basic risk management facilitation methods (Flow
    charts, check sheets etc.).
  • Failure Mode Effects Analysis (FMEA).
  • Failure Mode, Effects and Criticality Analysis
    (FMECA).
  • Fault Tree Analysis (FTA).
  • Hazard Analysis and Critical Control Points
    (HACCP).
  • Hazard Operability Analysis (HAZOP).
  • Preliminary Hazard Analysis (PHA).
  • Risk Ranking and Filtering.
  • Supporting Statistical Tools.

41
Importance of Communication in QRM
Communicationfacilitates trust and understanding
Industryoperation - Submissions - Manufacturing
Regulatorsoperation- Reviews - Inspections
42
Using ICH Q9 will
  • Facilitate
  • Communication and transparency
  • More informed, scientifically based decision
    making
  • Patient focused actions on quality risks
  • Realistic and appropriate solutions
  • Use of existing solutions (Share best
    practice/prior knowledge)
  • Manage critical to quality aspects
  • Through systems, organisations, processes
    products
  • Maintain responsibility accountability for QRM
  • Focus activity towards patient protection
  • It should never be used as a hobby horse /
    preconceived idea

43
Opportunity for the Industry Competent
Authorities
  • Using the same guideline apply QRM to industry
    (Development Manufacture) and regulators
    (Reviewer Inspectorate)
  • Provides for establishing a defined program for
    what we already do every day in our jobs
  • Supports science-based decision making
  • Optimisation of resources
  • Prevention from overly restrictive and
    unnecessary requirements
  • Facilitates communication and transparency

44
Challenges for Industry Competent Authorities
  • Interpreting and adopting the concepts of
    quality risk management into specific areas
  • Embed this behavior into quality aspects of
    business, technology and regulation
  • Adopt in existing structures, organizations and
    Quality System
  • Balance the documented use of informal and
    formal quality risk management

45
QRM Integration into Industry Reg Operations
  • QRM is a process that supports science-based and
    practical decisions when integrated into quality
    systems.
  • Effective QRM can facilitate better and more
    informed decisions.
  • Effective QRM can provide regulators with greater
    assurance of a companys ability to deal with
    potential risks.
  • QRM can facilitate better use of resources by all
    parties.
  • Training of both industry and regulatory
    personnel in QRM processes provides for greater
    understanding of decision-making processes
    builds confidence in QRM outcomes.

46
The new paradigm
risk-based concepts and principles
47
Incremental steps
Pharmaceutical Development (Q8) Past Data
transfer / Variable output Present Knowledge
transfer / Science based / Consistent output
Quality Risk Management (Q9) Past Used, however
poorly defined Present Opportunity to use
structuredprocess thinking
Pharmaceutical Quality Systems (Q10) Past GMP
checklist Future Quality Systems across product
life cycle
Q8
Q10
Q9
48
How Q9 interacts with Q8 and Q10
Risk from Manufacturing site
High
Q10 Pharm. Quality Systems
Low
Q8 Pharmaceutical Development
Low
High
Product / Process Risk
49
ICH Q9 Link back to patient risk
Opportunities to impact risk using quality risk
management
Q8
Q9
Design
Q10
Process
Materials
Manufacturing
Facilities
Distribution
Patient
50
A Vision of the Future
  Old Approach New Approach Remarks
Broad Concept Quality decisions divorced from science and risk evaluation.Adherence to filing commitments. Quality decisions and filing committments based on Process Understanding and Risk Management.Quality by Design. Design Space concept introduced to integrate process knowledge with regulatory evaluation.
Quality Post-factum sampling and quality testing.Process Validation. Management of variabilityProcess control focused on critical attributes.Continuous Quality Verification. Quality by design definition applied. Measure critical process parameters to control output product quality.
Systems Systems designed to inhibit changes minimize business risks. Discourages improvement innovation. Changes managed within company's quality system.Real time batch release feasible. Regulators and industry place higher reliance / trust / understanding on systems.Multidisciplinary evaluation and decision making.
Regulatory Compliance focus.Changes require prior approval. Regulatory scrutiny adjusted to level of Process Understanding. Continuous improvement allowed within Design Space. Requires mechanisms to communicate Process Understanding data ("inspectable rather than reviewable").
51
  • Regulatory Guidelines
  • Read Repeat Ruminate
  • raison d'être (French underlying principle)
  • THANK YOU !
About PowerShow.com