1_System Approach for Pharmaceutical Products

8/2/2019 1_System Approach for Pharmaceutical Products

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Pharm acopeial Educat ion

© 2008 United States Pharmacopeial Convention All Rights Reserved V.1.0

Pharmaceutical Development, Quality Risk

Management and Pharmaceutical Quality:System Approach for Pharmaceutical

Products - ICH Q8, Q9 and Q10

Barbara B. Zinck

USP Pharmacopeial Education Consultant



Pharmacopeial Educat ion

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Topics

Quality and QA vs. QC

ICH - International Conference on Harmonization

ICH Q8 - Pharmaceutical Development

ICH Q9 - Quality Risk Management

ICH Q10 - Pharmaceutical Quality System

Opportunities and Benefits




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Qual i t y

Quality is the suitability of a drug substance or adrug product for its intended use

Identity Strength

Purity

Efficacy Safety

Quality cannot be tested into products. Qualityshould be built in by design

Quality is a result of planned programs and

commitment. It doesn’t just happen!




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Qu a l i t y Assu r ance an d Qu a l i t y Con t r o l

Qu al i t y Assu r ance - an overall umbrella group of people or a department designated to assure that

quality measures are in place, effective, measurable,and part of an overall quality process and system.

Qu a l i t y Con t r o l - focuses on individual testing unitswithin a manufacturing process such as thepackaging components, facility systems (water,

HVAC, envir testing) release assays, etc.) to producedata to ensure products meet requirements(specifications) and parameters of reproducibility.




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I CH

International Conference on Harmonization (ICH)of Technical Requirements for Registration of

Pharmaceuticals for Human Use

US, Europe and Japan

Regulators and Industry Quality, Safety, Efficacy and Multidisciplinary

Topics

ICH developed harmonized guidelines to establishrisk management framework for pharmaceutical

quality




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I CH Q8 , Q9 , Q1 0

I CH Q8 Pha r m aceu t i ca l Deve lopm en t

Guidance on scientific approaches and quality risk

management to the development of a product and itsmanufacturing process (FR 5/22/06)

I CH Q9: Qua l i t y Risk Man agem ent

Principles and examples of tools of quality riskmanagement that can be applied to all aspects of pharmaceutical quality (FR 6/2/06)

I CH Q10 : Ph arm aceu t i ca l Qua l i t y Sys t em

Modern quality systems to establish and maintain astate of control and facilitate continual improvement

over the life cycle of a drug product (FR 4/8/09)




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I CH Q8 – Ph ar m aceu t i ca lDeve lopmen t

Objective

Describes suggested contents for thePharmaceutical Development section of aregulatory submission

Covers product development andmanufacturing process

Degree of regulatory flexibility is based on the

level of relevant scientific knowledge provided

Scope – does not cover IND/clinical submissions




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Aim is to design a quality product andmanufacturing process to consistently deliver

the intended performance of the product

Pharmaceutical development information,

knowledge and manufacturing experienceprovide scientific understanding to establishspecifications, manufacturing controls and

design space




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Design Space

Multidimensional combination and interactionof input variables (e.g. material attributes)and process parameters that provideassurance of quality

Working within the design space is not achange

Working outside the design space is a changerequiring regulatory approval

Proposed by applicant and approved byregulatory authorities




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Q8 Oppor t un i t i es

More flexible regulatory approach

Risk-based regulatory decisions (reviews andinspections)

Manufacturing process improvements within

approved design space, without furtherregulatory approval

Reduction of post-approval submissions

Real-time quality control, leading to a reductionof end-product release testing

Q8 M f i P




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Q8 -Manu fact u r ing Pr ocessDeve lopmen t

Control and Improvement of the ManufacturingProcess

Appropriate equipment Process validation

Continuous process verification

Justify drug product specifications Identify critical process parameters to monitor and

control

Reliably produce a quality product

Process robustness useful in risk assessment

Future manufacturing and process improvements




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Q8 – Qu al i t y b y Desig n

Quality by Design (QbD)

Systematic approach to development

Predefined objectives

Requires product and process understanding

and process control

Based on sound science and quality riskmanagement

Can improve quality of product

Help regulators better understand company’s

strategy

Q8 E l f Di f f i A h




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Q8 Ex am p le o f Di f f e r ing Appr oach est o Phar m aceu t i ca l Deve lopm en t

Manufacturing Process- Minimal Approach

Fixed

Validation primarily

based on initial full-scale batches

Focus on optimization

and reproducibility

Manufacturing Process -Enhanced, Quality byDesign Approaches

Adjustable within designspace

Lifecycle approach to

validation and ideallycontinuous processverification

Focus on controlstrategy and robustness

Use of statistical processcontrol methods




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I CH Q9 – Qu a l i t y Ri sk Man a g em en t

Quality Risk Management - systematic processfor assessment, control, communication and

review of risks to quality of drug across productlife cycle

Risk management used in other governmentagencies and businesses such as finance,insurance and OSHA

Risk to Consumer / Patient – Prime Importance Safe, Efficacious, Availability of product to

patients

Q9 Qu a l i t y Ri sk Man ag em en t




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Q9 – Qu a l i t y Ri sk Man ag em en tBene f i t s

Provides a framework for quality and compliancedecision making

Assess state of compliance

Identify compliance risks

Prioritize and focus GMP oversight activities atdifferent levels

Focus on what is critical to quality

Ensure high risks are compliant

Minimize resources consumed on low risks

Ensures optimal use of regulatory and technical

resources




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Q9 – Pr i n cip les

Principles of Quality Risk Management

Evaluation of risk to quality should be basedon scientific knowledge

Link to protection of patient

Level of effort, formality and documentation of the quality risk management process should becommensurate with the level of risk

Not intended to create any new expectationsbeyond current regulatory requirements





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Q9 – Qu a l i t y Ri sk Man ag em en tProcess

Include Risk Management Tools and RiskCommunication throughout quality risk

management process

Initiate Quality Risk Management Process –

define problem, identify potential for risk andlevel of decision making

↓↓

Risk Assessment – identify hazards andevaluation of risks associated with hazards





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Risk Assessment

Risk Identification – What might go wrong?

Risk Analysis – estimation of risk associatedwith hazard

Risk Evaluation – compare identified and

analyzed risk against risk criteria

↓↓

Risk Control – includes decision making toreduce and/or accept risks to an acceptablelevel

Q9 – Qu a l i t y Ri sk Man ag em en t




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Risk Control

Risk Reduction – mitigate or avoid risk when

it exceeds a specified/acceptable level Risk Acceptance - accept risk that is reduced

to an acceptable level

• Cannot always entirely eliminate risk

↓↓

Output / Result of the Quality Risk ManagementProcess

Q9 – Qu a l i t y Ri sk Man ag em en t




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Output / Result of the Quality Risk ManagementProcess – Risk communication and sharing

information about risk and risk managementbetween the decision makers and others

↓↓

Risk Review

Review and Monitor Events – frequency of review should be based upon the level of risk

I CH Q1 0 – Ph a rm aceu t i ca l Qu a l i t y




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I CH Q1 0 Ph a rm aceu t i ca l Qu a l i t ySystem

Should facilitate innovation and continualimprovement and strengthen the link betweenpharmaceutical development and manufacturing

(Complements Q8 and Q9)

Can be implemented throughout the different stagesof a product lifecycle

Applies to development and manufacture of drugsubstances/APIs, drug products and biotechnologyproducts

ICH Q10 augments GMPs

Regional GMPs do not explicitly cover productdevelopment




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Q1 0 – En ab ler s

Use of Quality Risk Management and KnowledgeManagement will enable a company to

implement Q10 effectively and successfully

Quality Risk Management – systematic process

for assessment, control, communication andreview of risks to the quality of drug productacross the product lifecycle (ICH Q9)

Company-wide and site-specific aspects Quality Manual – include description of

pharmaceutical quality system

Q1 0 K l d M




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Q1 0 – Kn ow led ge Man ag em en t

Knowledge Management

Systematic approach to acquiring, analyzing,

storing and disseminating information

• Prior knowledge, pharmaceutical developmentstudies, technology transfer, process validation,

manufacturing experience, innovation, continualimprovement, APRs, etc.

Enables implementation of concepts described in

Q8, Q9 and Q10

Q1 0 M t R i b i l i t




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Q1 0 – Man a g em en t Resp o n si b i l i t y

Management commitment - senior management leadershipis responsible and essential to establish, resource andmaintain a company-wide commitment to quality

Quality policy

Quality planning

Resource management

Internal communications

Management review

Management of outsourced activities and purchasedmaterials

Management of change in product ownership

Q1 0 El t f PQS




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Q1 0 – El em en t s o f PQS

Elements of a Pharmaceutical Quality System(PQS)

Process performance and product qualitymonitoring system

Corrective action and preventive action (CAPA)

system Change management system

Management review of process performance

and product quality Apply as appropriate to each of the product

lifecycle stages

Q1 0 P f d M it i




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Q1 0 – Per f o r m an ce an d Mo n i t o r in g

Process performance and product qualitymonitoring system

Ensure a state of control is maintained

Produce a product of desired quality

Identify areas for continual improvement

Use quality risk management to establishcontrol strategy

Continual improvement of pharmaceutical qualitysystem (PQS)

Management review of PQS

Q1 0 – Ch a n g e Man a g em en t Ap p l icat i on




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g g p pt h r oug hou t Pr odu ct L i f ecycle

Pharmaceutical Development

Change is part of development and should be

documented Less formal process

Technology Transfer

Provide management and documentation of changes made to process

Commercial Manufacturing Formal change management system with QA

oversight – science & risk assessments

Product Discontinuation

Q8 , Q9 , Q1 0 Opp or t u n i t ies and




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, , ppBene f i t s

Demonstrate effective pharmaceutical qualitysystem and product and process understanding,

including the use of quality risk management

Opportunities and Benefits of using Quality Risk

Management Principles, ICH Q8, Q9, Q10

Increase use of risk based approaches forregulatory inspections

Facilitate science based pharmaceutical qualityassessments

Oppor t un i t i es and Bene f i t s




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Oppor t un i t i es and Bene f i t s

Opportunities and Benefits of using Quality RiskManagement Principles, ICH Q8, Q9, Q10

Establish and maintain a state of control

Enable innovative approaches to process

validation

Establish real-time release mechanisms

Optimize science and risk based post-approvalchange processes to maximize benefits frominnovation and continual improvement

I CH Q8 Q9 an d Q1 0




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I CH Q8 , Q9 an d Q1 0

Questions?

Thank you

Documents

1_System Approach for Pharmaceutical Products