Process and Software Validation

Course Outline

I. Introduction to Process Validation

• Regulatory Perspective
  • Understand the importance of process validation from a compliance perspective
  • Recognize the role process validation plays in understanding process and product variability
  • Understand the perspectives of the FDA, international regulators and the GHTF
  • Appreciate the consequences of non-compliance, a review of recent Warning Letters and Consent  Decrees
• Process Validation Requirements
  • Requirements of 21 CFR Part 810.75
  • Requirements of ISO 13485:2003 and ISO 14971
  • Recommendations of GHTF N99-10
  • 21 CFR 211, ICH- Guidance
  • Difference between validation, verification, qualification, commissioning
  • Approaches to validation (i.e. prospective, concurrent and retrospective validation)
• Elements of Process Validation Master Plan
  • Master Validation Plan
  • Site Master Plan
  • Assessing the status of existing systems
  • Identifying the systems to be validated
  • Assigning the priority and importance
  • Defining and controlling the Master Validation Plan (MVP)
  • An audit perspective of the Validation Master Plan

Group Exercise: “Create Validation Master Plan”

II. Process Validation System

• Implementing a Documented Validation System
  • Documented Validation System
  • Design, Installation, Operation and Performance qualifications
  • Validation protocols and reports
  • Application of risk management to process validation
  • Training and competence
  • Determining when revalidation is required
  • Change Control

Group Exercise: Analysis of a Validation Protocol

Group Exercise: Write a Validation Standard Operating Procedure

III. Designing a Validation Protocol

• The Process Validation Steps
  • Design Qualification
  • Installation Qualification
  • Operation Qualification
  • Process Qualification
  • Defining the protocol
  • Executing the protocol
  • Documenting the results of the validation
  • Discrepancies during validation
  • Protocol deviations and failures
• Validation Protocol Design
  • Establishing the objective
  • Defining the critical process parameters
  • Defining tests to perform
  • Defining acceptance criteria
  • Deviation report & Log
  • Use of the protocol as the report
  • Role of measurement and analysis
• Installation Qualification
  • Manuals
  • Equipment life cycle
  • Preventive maintenance
  • Calibration
  • Utilities
  • Remedial maintenance / moves
  • Requalification

Individual Exercise: Write an IQ Protocol

• Operation Qualification
  • Operations Manuals
  • Determining functions to test
  • Programming vs. parameter entry
  • Standards
  • Recording observations
  • Difference between OQ and Capability Studies, and purpose of each

Individual Exercise: Write an OQ Protocol

• Process Qualification / Process Validation
  • Statistical Tools of Process Validation
    • Averages, medians, mode and standard deviation
    • Cpk or process capability
    • Control charting to monitor performance
    • T-tests, ANOVAs and F-tests
    • Design of Experiments
    • Data handling and data analysis
  • Trials
  • Determining Acceptance Criteria
  • Classical Design Space

Individual Exercise: Participants will develop test criteria for a Validation Protocol

IV. Executing a Validation Protocol

V. The Validation Life Cycle

• Re-validation
  • When, why and what
  • Handling problems during re-validation
  • Product and process implications
• Product complaints and process failures
  • Evaluating process parameters as a cause of product failures
  • Design changes
  • Process change history
  • Role of corrective action and FMEA
  • Amending the existing MVP

VI. Software Validation

• Software Validation
  • Scope of implementation
  • System control, roles and responsibilities
  • Electronic records and electronic signatures
  • System requirements through to validation
  • Handling and assessing source code
  • Role and importance of the traceability matrix
  • Defining and executing test scripts
  • System validation
  • Software customization and changes/updates

VII. Closing