Molecule-to-Market-Place
Quality
Dawn Sanchez-Barona, PhD
Senior Director, Quality Control
Quality Operations
Eisai Inc.
Overview
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Role of Quality Operations
Principles of Quality Management
Example of Quality Operations Organization
Responsibilities of Each Quality Department
Quality Operations in Pharmaceutical and Analytical
Development
 Quality Strategy in Pharmaceutical Development
References
 Q7A – Good Manufacturing Practice Guide for Active
Pharmaceutical Ingredients
 Q8 – Pharmaceutical Development
 Q9 – Quality Risk Management
 The Gold Sheet, Vol. 40, August 2006
www.ich.org
www.FDA.gov/cder/handbook/development.htm
Role of Quality Operations
Ensure (Eisai) patients receive clinical or commercial
products that are safe, pure, and fit for their intended
use, and comply with all regulatory requirements.
Principles of Quality Management
 All persons involved in manufacturing pharmaceutical products
are responsible for quality.
 Each manufacturer should establish, document, and implement
an effective system for managing quality that requires the
commitment and active participation of management and staff at
all levels in the company – as well as the company’s suppliers,
contractors, and distributors.
 There should be a quality unit(s) that is independent of
production and that fulfills the quality assurance (QA) and
quality control (QC) responsibilities.
 Quality-based decisions are based on sound scientific judgment
and evaluation and require defined processes to implement.
Example of Quality Operations
Organization
Manufacturing QA
Clinical QA
QC
Validation
Responsibilities – Manufacturing QA
Broadly responsible for implementation and adherence to GMPs,
product disposition, and quality systems associated with these
functions:
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Document Control
Auditing/Vendor Certification
Training
Product Dispositions
Deviations/Investigations/Corrective Actions/Preventative Actions
Change Control
Label Review and Disposition
Reserve/Retain Sample Management
Complaints
Trending
Annual Product Reviews
Contract Manufacturing Organizations
Responsibilities – QC
Broadly responsible for laboratory controls associated with
product disposition and quality systems required for this
function:
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Sampling/Disposition Raw Materials and Packaging Components
GMP Laboratory Management
Release Testing
Stability Testing and Program Management
Document Control/Evaluation
Out-of-Specification Investigation
Reference Standard Management
Analytical Technology Transfer/Validation
Analytical Evaluation of Post-Market Changes
Investigation Support
Responsibilities – Validation
Broadly responsible for establishing a validation program and
compliant documentation and execution of all qualification and
validation activities, including:
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Equipment Qualification
Computer System Validation
Cleaning Validation
Process Validation
Periodic Review of Validated Systems
Risk Assessment
Responsibilities – Clinical QA
Broadly responsible for ensuring clinical trials are
conducted in accordance with GCPs, and that data
are generated, documented, and reported accurately
and in compliance with all applicable regulatory
requirements.
Quality
Manufacturing QA
Validation
Clinical QA
QC
Quality Operations in
Pharmaceutical and Analytical
Development
The New Drug Development Process
Steps from Test Tube to New Drug Application Review
Quality Operations in Pharmaceutical
and Analytical Development
 Goals are same; i.e, role of Quality Operations and
principles of Quality Management does not change.
 Tactics for implementing quality can be different.
 Controls used in the manufacture of active pharmaceutical
ingredients (APIs) and drug products should be consistent
with the stage of development.
 Process and test procedures should be flexible to provide for
changes as knowledge of the process increases, and clinical
testing of a drug product progresses from pre-clinical
through clinical stages.
Responsibilities – Manufacturing QA
Broadly responsible for implementation and adherence to GMPs,
product disposition, and quality systems associated with these
functions:
•
•
•
•
•
•
•
•
•
•
•
•
Document Control
Auditing/Vendor Certification
Training
Product Dispositions
Deviations/Investigations/Corrective Actions/Preventative Actions
Change Control
Label Review and Disposition
Reserve/Retain Sample Management
Complaints
Trending
Annual Product Reviews
Contract Manufacturing Organizations
Responsibilities –
Analytical Development
Testing functions commonly performed by QC can be performed within
other organizational unit, such as Analytical Development (AD).
In this example, AD would be broadly responsible for laboratory
controls associated with clinical product disposition and quality systems
required for this function:
•
•
•
•
•
•
•
•
•
•
Sampling/Disposition Raw Materials and Packaging Components
GMP Laboratory Management
Release Testing
Stability Testing and Program Management
Document Control/Evaluation
Out-of-Specification Investigation
Reference Standard Management
Analytical Technology Transfer/Validation
Analytical Evaluation of Post-Market Changes
Investigation Support
Responsibilities – Validation
Broadly responsible for establishing a validation program and
compliant documentation and execution of all qualification and
validation activities, including:
•
•
•
•
•
•
Equipment Qualification
Computer System Validation
Cleaning Validation
Process Validation
Periodic Review of Validated Systems
Risk Assessment
Quality Strategy in Pharmaceutical
Development
Theme – Quality by Design (QbD)
 Knowledge of process (design space)
 Identification of steps critical to quality of drug
substance or drug product
 Control strategies for synthesis/formulation choices
justified
Background
 PD Goal – Design a quality product and
manufacturing process to consistently deliver the
intended performance of the product.
 Information and knowledge gained from
pharmaceutical development studies provide:
 Scientific basis for establishing the formulation design space,
specifications, and manufacturing controls
 Rationale for quality risk management
Background
 Design Space
 Multidimensional combination and interaction of input
variables (e.g., material attributes) and process parameters
that have been demonstrated to provide assurance of
quality.
 Proposed in (NDA) filing and subject to regulatory (FDA)
assessment.
 Working within design space not considered a change.
 Movement out of design space considered a change and
would initiate a typically regulatory post-approval filing.
Establishing Design Space: Gains
 Creates higher degree of understanding of material attributes,
manufacturing processes and their controls within your company
and with FDA.
 Facilitates understanding of differences between the
manufacturing processes used to make drug product for pivotal
clinical trials/stability studies and vs. commercial product
 Provides potential opportunities for risk-based regulatory
decisions (reviews and inspections)
 Facilitates manufacturing process improvements without further
regulatory review (if stay within design space) and may reduce
number of post-approval submissions
 Provides potential for real-time quality control and reduction of
end-product (QC) release testing
Establishing Design Space:
Challenges
 Establishing appropriate/expected level of detail in
regulatory submissions
 Establishing balance between QbD-based vs.
traditional demonstration of quality
 Achieving regulatory flexibility while assuring product
quality
 Sharing proprietary information with FDA
 FDA pilot program – more work to be done!