The New Quality Paradigm in Ich q8 q9 q10 q11

8/12/2019 The New Quality Paradigm in Ich q8 q9 q10 q11

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THENEWQUALITYPARADIGMINICH Q8 Q9 Q10 Q11OPPORTUNITIES ANDEXPECTATIONS

DR. [email protected]


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Why do we need itSome background Information

THENEWPARADIGMOR

QUALITYBYDESIGN


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GLOBALHARMONISATION(ICH+GCG)

Expert WorkingGroups (EWG)

WHO Global Cooperation Group

APEC

ASEAN

PANDRH

SADC

www.ich.org

The impact of ICH


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THEROLEOFPROCESSUNDERSTANDING

Pharma Air Plane

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Typical Ingredients of a Tablet

Active 5m

Corn Starch 30m

Lactose 100m

MicrocrystallineCellulose 102100m

Dr. Susanne Keitel

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Pharmaceutical Development Q8Defines what is the minimum (Basel Line)

The role of Process Understanding

Defines what is a Design Space

Defines Regulatory FlexibilityPharmaceutical Development Q8 AnnexDefines what is Quality by Design

The role of a Systematic Approach

Defines Critical Quality Attribute

Examples of Design Space

Defines Control StrategyDevelopment of Drug Substances Q11Defines what is the minimum (Basel Line)

The traditional and enhanced Approaches

Defines Critical Quality Attributes (CQAs)

How to use Quality Risk Management

The newParadigm

QAnnex

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The New Paradigm Quality by DesignHEICH CONCEPTOFTHENEWPARADIGM


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A PROCESSISWELLUNDERSTOODWHEN all critical sources of variability areidentified and explained; variability is managed by the process; and, product quality attributes can beaccurately and reliably predicted over thedesign space

The PAT Guidance

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ICH Q8(R) : DEFINITION

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Quality by Design:

A systematic approachto development

that begins with predefined objectives and emphasizesproduct and process understandingand process

control, based on sound science and quality risk

management.


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WHATISQUALITYBYDESIGN

Elements of a QbD

Systematic Development Approach

Formulation UnderstandingProcess Understanding

Packaging Understanding

Application of Quality Risk Management

Advanced Control Strategy

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TRADITIONALVERSUSENHANCEDDEVELOPMENT


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Conventional PD Quality by Design(ideal)

Mainly empirical approach A systematic approach

Quality assured by end-

product testing and

inspection

Quality assured by well understood

product and process, moving controls

upstream without relying only on end-

product testing justified in aControl Strategy

Process is fixed, disallowing

changes

Flexible process within design space,

allowing continuous improvement

Focus on process

reproducibilityoften

avoiding or ignoring

variability

Focus on formulation and process

robustnessunderstanding and

controlling variability

Limited and simple IPC

Control Strategy based on end

product testing

Extended PAT tools replacing the need for

end product testing

Extended Control Strategy based on QRM

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Q8 GENERALCONCEPTS: REGULATORYFLEXIBILITYThis scientific understanding facilitates

establishment of an expanded design space. In these

situations, opportunities exist to develop more

flexible regulatory approaches, for example, to

facilitate:

risk-based regulatory decisions (reviews and

inspections);

manufacturing process improvements, within theapproved design space described in the dossier,

without further regulatory review;

reduction of post-approval submissions;

real-time quality control, leading to a reduction of

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POSSIBLEREGULATORYFLEXIBILITY

Continuous Improvement

Real time release Reduced or elimination of routine end product testing

Expanded design space Independence on scale Independent of equipment Independent of site Independent from drug substance manufacturing if within spec

Process Validation Process validation replaced by Concurrent Process Verification using validated

methods (qualified controls)

Stability Testing Reduced confirmation stability studies for any changes within the design space Reduced annual stability batches

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ADDITIONALBENEFITSOFQBD

Faster DevelopmentBetter FormulationsBetter ProcessLess Rejects and OOS OOELess QA investigationsMore consistent and reliable QualityReduced manufacturing costLess Transfer problems

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Q8 GENERALCONCEPTS

WHATISMINIMALREQUIREMENT

At a minimum, those aspects of drug

substances, excipients, container closure

systems, and manufacturing processes thatarecritical to product qualityshould be

determined and control strategies justified.

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Q8 GENERALCONCEPTS

WHATISCRITICAL?

Critical formulation attributes and process

parameters are generally identified through anassessment of the extent to which their variation

can have impact on the quality of the drug product.

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ICH Q11

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For Drug Substance from

Chemical Origin

Biotech Origin

Q11 SCOPE

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Manufacturing process development shouldinclude, at a minimum, the followingelements: Identifying potential CQAs associated withthe drug substance so that thosecharacteristics having an impact on productquality can be studied and controlled; Defining an appropriate manufacturingprocess; Defining a control strategy to ensure processperformance and drug substance quality (seeSection 6 on Control Strategy).

MINIMUMREQUIREMENTS

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An enhanced approach to manufacturing processdevelopment would additionally include the followingelements:

A systematic evaluation and scientific understanding ofthe manufacturing process, including use of QRM;

Determination of the functional relationships andrelevant multivariate interactions that link materialattributes and process parameters to drug substanceCQAs; Using the enhanced approach in combination with QRM toestablish a more focused control strategy which caninclude proposals for a design space(s).

Q11 ENHANCEDAPPROACH

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For drug substance development amajor focus is knowledge andcontrol of impurities

IMPORTANCEOFIMPURITIES

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Risk assessment can be used duringdevelopment to identify those parts of theprocess likely to impact potential CQAs anddrive process improvement to mitigate qualityrisk. Further risk assessments can be used tofocus development work in areas where betterunderstanding of the link between process andquality is needed

THEROLEOFRISKMANAGEMENT(QRM)

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Identify potential sources of process variability; Identify the material attributes and process parameterslikely to have the greatest impact on drug substancequality. This can be based on prior knowledge and riskassessment tools; Design and conduct experiments and/or mechanistic studies(e.g., multivariate Design of Experiments, simulations,modelling) to identify and confirm the links andrelationships of material attributes and process parametersto drug substance CQAs; Conduct analysis of the data to establish appropriateranges, including establishment of a design spaceifdesired.

ENHANCEDAPPROACH

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Every drug substance manufacturing process,whether developed through a traditional or anenhanced approach (or some combination thereof),has an associated control strategy.

A control strategy can include, but is notlimited to, the following: Controls on material attributes (including raw materials,starting materials, intermediates, reagents, primary packagingmaterials for the drug substance, etc.); Controls implicit in the design of the manufacturing process(e.g., choice of reagents or media, sequence of operations); In-process controls (including in-process tests and processparameters); Controls on drug substance (e.g., release testing).

6. CONTROLSTRATEGY

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POINTSTOCONSIDER


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POSTAPPROVALCHANGEMANAGEMENTPROTOCOLS

+trategy Results +Strategy Results

CurrentlyEvaluation of a proposedvariation as a whole(Strategy + Results)

Early Step 1:

Submission of aChange ManagementProtocol

Fast Step 2:

Reporting ofimplementation of a changein accordance with anapproved protocol

Type II VariationType IAINor IB

Variation


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CONTENTOFAPOSTAPPROVALCHANGEMANAGEMENTPROTOCOL Support of the proposed change company should submit all relevant information

that can demonstrate that it has acquired adequateknowledge

to prepare and

manage the impact of the change.

The content of the protocol could includedepending on the nature of the change: Justification that there is a definite recognised

future need for the specific change,

within a reasonable timeframe,

and that adequate knowledge has been acquired toappropriately evaluate and manage the change for the specificproduct concerned.

Justification should also be provided for the proposedevaluation strategy.


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SUMMARYQ8, Q9, Q10, Q11 define a new ParadigmSystematic Development ApproachFormulation UnderstandingProcess UnderstandingPackaging UnderstandingApplication of Quality Risk ManagementAdvanced Control Strategy


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QUALITYBYDESIGN:

The Future has started

QbD submissions approved in US and EUincluding Real Time ReleaseNEW : also for BIOTECH Products

The New Quality Paradigm in Ich q8 q9 q10 q11

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