In-house Compliance Workshop

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Compliance Workshop 106

FDA/EU Compliance for Quality Control Laboratories

Requirements and Tools for Implementation

Course objectives

• Get a thorough understanding of FDA and international requirements
• Learn how to effectively implement and apply for day/-by-day lab operations
• Understand consequences of non-compliance
• Prepare your lab for successful FDA and international GMP inspections

Contents Overview

• FDA and international regulations and guidelines
• FDA inspection and enforcement practices
• Developing a laboratory compliance master plan
• Qualification of analytical equipment and computers
• Validation of analytical methods and procedures
• Development and validation of stability indicating methods
• Quality management of reference standards and reagents
• Sampling: sampling plan, representative sampling, documentation
• Sample handling: preventing deterioration and loss or damage
• Conduct and report testing and review, approval and and reporting resuls
• Managing failure investigations and OOS results
• Maintenance and archiving of paper and e-records
• Developing an FDA compliant training plan
• Writing FDA compliant procedures
• Preparation for FDA inspections

Detailed Agenda

FDA and International Regulations and Guidelines

• 21 CPR Part 211 (GMP)
• 21 CFR Part 11 (Electronic records & signatures)
• EU GMP, Annex 11
• Inspection guides (FDA, PIC/S)
• Most frequently cited deviations
• Examples of warning letters and inspectional observations

Developing a Laboratory Compliance Master Plan

• Scope and objectives
• Laboratory compliance master plan or quality plan?
• Contents of the plan
• Responsibilities
• The development process
• Communication of the plan

Equipment Qualification and Maintenance

• FDA requirements
• USP chapter <1058> for analytical instrument qualification
• The equipment qualification life-cycle: 4Q model
• Qualification steps: DQ, IQ, OQ, PQ
• Procedures and deliverables for USP <1058> categories
• Managing and recording changes
• Equipment maintenance program

Validation of Computerized Analytical Systems

• FDA and international requirements
• Developing a master and project plan
• Validation steps from specifications to retirement
• What and how to test for commercial systems
• Configuration management and change control
• Validation of Excel spreadsheets
• Revalidation and review

Method Validation and System Suitability Testing

• FDA guidance for method validation
• Procedures for method validation
• Selection of test parameters and acceptance criteria
• Documenting validation results
• Verification of standard methods
• 'Adjustment vs. change'
• Transfer of methods
• Type and frequency of system suitability testing

Sampling, Sample Handling and Testing

• Developing a sampling plan
• The sampling system: selection, documentation
• Representative sampling: a major FDA concern
• Preventing deterioration during sample transfer
• Keeping reserve samples: how long, how much
• Setting test specifications

Documentation, Review and Approval of Test Results

• Documenting results
• Procedure for review of test results
• Review by the analyst: what to look at, how to document
• Review and approval by a second person
• Release of test results

OOS/Failure Investigations

• FDA regulations and guidelines
• FDA's final guidance on Investigating OOS test results
• Learning from recent FDA 483's and warning letters
• Developing SOPs for OOS situations and laboratory failures
• Managing formal and informal investigations in laboratories and manufacturing
• Retesting: when and what and how many times
• Developing corrective and preventive action plan
• Root cause analysis
• Strategies to avoid OOS situations BEFORE they occur

(Certified) Reference Standards and Other Supplies

• FDA and international requirements
• Hierarchy of (certified) reference material
• Procedures for purchasing, qualification, handling, labeling and storing reference material
• Qualification of the supplier: criteria and documentation
• Incoming quality control of chemicals, solvents and reference material
• Preparation and qualification of working standards from certified reference material
• Labeling chemicals: e.g., storage conditions expiration date

Risk Based Compliance and Validation in QC Laboratories

• FDA's 21st century drug CGMP initiative: risk and science based compliance
• Methods for risk management
• Developing a risk management master plan
• Define the risk category for a laboratory system and processes
• Define risk based validation tasks
• Workshop and example

Management of Laboratory Raw Data and Other Records

• Definition of raw data
• Acquisition and recording of raw data
• The importance of 21 CFR Part 11 for electronic records
• Maintenance, archiving and retrieval
• Archiving period
• The role and responsibilities of the archivist

Stability testing

• FDA and EU requirements
• ICH guidelines
• When is stability testing required
• Setting up the experiments
• Documenting results

SOP requirements: Type, formats and enforcement

• When are SOPs required
• Format of SOPs
• Writing, approval, distribution, obsolescence
• Managing electronic SOPs
• Examples for laboratory procedures

Training for GMP Compliance

• Most frequently cited deviations
• Developing an effective training program for a laboratory.
• Developing a training plan for individual employees
  Who can or should be responsible for the training program and training plans.
• Most efficient training tools for different tasks.
• Assessment of successful participation
• The benefits of risk based training
• Documentation of trainings for the FDA
• Specific training requirements for part 11

Documentation Requirements

• Overview of required documents
• Documentation control
• Electronic vs. paper documentation
• Typical documentation examples

Auditing Analytical Laboratories for FDA Compliance

• Three good reasons for laboratory audits
• FDA and international requirements for laboratory audits
• FDA Inspections as model for laboratory audits
• Developing an SOP for 'FDA Inspection Like' audits
• Developing an audit schedule
• The audit team: members, tasks, responsibilities
• Selecting most critical areas
• Looking at the right documentation
• Looking at critical laboratory subsystems
• Assessment through laboratory walkthrough
• Writing the audit report
• Follow-up with corrective and preventive actions

Collaborative Exercises, Discussions and Examples

Practical examples, case studies and collaborative exercises will be dispersed into and between the presentations. At least 50% will be dedicated to practical sessions with life examples. The outcome will be made available for all attendees on a special workshop reference website. Practical sessions include:

• Case study: We will present and analyze a lab compliance master plan for a QC lab with stability testing
• Workshop: Setting requirement specifications for equipment
• Workshop: Define what should be tested for a commercial computerized analytical system
• Workshop: List of validation tasks and associated deliverables along the equipment and computer system life. What needs to be done and documented when?
• Workshop: Documenting test results
• Workshop: Review and approval of test results
• Workshop: Retesting yes/no?
• Workshop: Criteria for suppliers of reference material
• Workshop: Determine risk categories for laboratory systems
• Example: Risk based validation tasks
• Workshop: Definition of raw data for combined electronic/paper based systems
• Workshops and examples
• Workshop: Managing deviations from SOPs
• Case studies: going through five example SOPs
• Workshop: Establish a training plan based on education, experience and tasks
• Workshop: List of validation tasks and associated deliverables along the equipment life. What needs to be done and documented when?
• Case study: Going through an example package for equipment qualification
• Workshop: Attendees will be presented several FDA Warning letters for QC Laboratories. Attendees will suggest responses and preventive and corrective actions.
• Example: We will go through a laboratory audit checklist

10+ Reference documents for easy Implementation

The documents can be downloaded from a dedicated seminar website.
They include

• SOPs:
  - Handling OOS results
  - Laboratory Failure Investigations
  - Validation of Laboratory Computer Systems
  - Validation of Chromatographic Methods
  - Qualification of Equipment
  - Validation of Electronic Laboratory Notebooks
  - Validation of Spreadsheet Applications
  - Change control of analytical equipment
  - Development and Maintenance of Test Scripts
• Worksheets/Checklists/Examples
  - Laboratory Audits
• Reference Articles
  - Implementing 21 CFR Part 11 in Laboratories
  - Preventing Out-of-Specification Situations
  - Selecting parameters and limits for equipment qualification
  - Preparation and qualification of (certified) reference material
• FDA Presentations and Reports
  - Laboratory inspections
• Drug cGMP Requirements for Laboratory Records
• Warning letters and/or Inspectional observations related to Analytical Laboratories
• FDA Guidance for Industry:
  Inspection of Quality Control Laboratories

Who should attend

• FDA/EU regulated laboratories
• Analysts and lab managers
• QA managers and personnel
• Validation specialists
• Regulatory affairs
• IT professionals
• Human resources (HR) managers and staff
• Training departments
• Documentation department
• Consultants. teachers
• Teachers

About the speaker: Dr. Ludwig Huber

• Chairman, presenter and panel discussion member at US-FDA Industry Training sessions and conferences
• Team and/or review member of PDA's task forces "21 CFR Part 11", of US-FDA internal documents, and of the GAMP special interest group on Laboratory Equipment
• Presenter of the Year of the Institute for Validation and Technology
  Director and chief editor of www.labcompliance.com, the global on-line resource for validation and compliance issues.
• Author of the books “Validation and Qualification in Analytical Laboratories, and "Validation of Computerized Analytical and Networked Systems", Interpharm Press
• For more information on Ludwig Huber, click here.

Dr. Ludwig Huber is a frequent presenter at IVT conferences and has been awarded as the 'Presenter of the Year' out of 170 speakers. This photo is from IVT's conference on Network Qualification with Ludwig Huber as plenary speaker.