MoleculetoMarketPlace Quality

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Molecule-to-Market-PlaceQuality

• Dawn Sanchez-Barona, PhD
• Senior Director, Quality Control
• Quality Operations
• Eisai Inc.

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Overview

• 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

3
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

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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.

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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 companys
  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.

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Example of Quality Operations Organization
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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

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Responsibilities QC

• Broadly responsible for laboratory controls
  associated with 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

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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

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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.

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Quality
Clinical QA
Manufacturing QA
QC
Validation
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• Quality Operations in Pharmaceutical and
  Analytical Development

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The New Drug Development ProcessSteps from Test
Tube to New Drug Application Review
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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.

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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

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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

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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

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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

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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

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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.

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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

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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!

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