GMP Compliance for Biopharmaceuticals AND GMP for Advanced Therapy Medicinal Products

Programme

GMP Compliance for Biopharmaceuticals

GMP Requirements Applying to Biotechnological Investigational Medicinal Products (IMPs of Clinical Phases I-III & APIs for use in IMPs)

• EU regulations & guidances
• Examples of national regulations
• State-of-the-art manufacturing for clinical phases

GMP Guidelines for Biopharmaceuticals – a brief summary

• Relevant international regulations
• European biotech guidances
• Recent developments & possible impacts

Development of Biopharmaceuticals - GMP and Regulatory Aspects

• GMP and Regulatory Documents
• Ways to Success
• Interaction with Authorities (Meetings/Inspections)

Development, Qualification and Validation of Process Analytics for Biopharmaceuticals

• Relevant Guidelines
• Phases of Product Development / Testing
• Requirements
• Method Portfolio/Method Development / Method Qualification / Method Validation

GMP Inspections in Biopharmaceutical Production

• Inspections of biopharmaceutical companies
• Focus & discussion points during inspections
• Clean room classes for biotech facilities
• Open vs. closed processing
• Single - vs. multi purpose equipment
• Cell banking activities
• Inspector’s experience, examples of observations

Case Study: Process Transfer from Development to commercial Production

• Key-Aspects for EU and US
• Difference between Development and Commercial Production
• Case Study

Quality Assurance for Biopharmaceuticals

• Classical responsibilities of QA department
• Allocation of responsibilities, training of staff
• Dealing with suppliers & contractors
• The world changes: Change management
• Shit happens: Deviation management & CAPA
• Handling complaints &product recalls
• Paper, paper, paper: documentation works: SOPs, MBR, PQR & management report
• Surveillance of qualification & validation, calibration and maintenance
• Self inspections & auditing

Process Validation in Clinical Phases I-III

• Definition of Validation
• Validation in early Clinical Phase
• Validation in late Clinical Phase
• Validation Documentation
• Guidelines

State-of-the-art biotechnological manufacture (bacteria, yeast, mammalian cells) and cell banking activities - Part 1

• Reasons for cell banking
• Where does GMP start
• Characterization of cell banks
• Storage of cell banks

State-of-the-art biotechnological manufacture (bacteria, yeast, mammalian cells) and cell banking activities - Part 2

• Overview of a typical biotech process
• Requirements on production areas, raw materials
• and equipment
• Specialities on biotech products
• Fill and finish

Workshop:
Case Studies Hygienic GMP Deviations

• Examples of Pitfalls
• Chemical Interactions
• Human Errors
• Incorrect use

Prevention of cross contamination: dedicated manufacturing or cleaning validation?

• Requirements of Chapter 3 and 5 and Annex 2
• Decision with Consequences: Multipurpose
• Equipment or Disposables
• Dirt or Product: The Perspective Defines Contamination
• Ways to Remove Contaminants: Cleaning
• Procedures and their testing
• Risk Based Approach: Crucial Element of the Validation Programme

GMP for Advanced Therapy Medicinal Products (ATMP)

Tissues, Tissue Preparations and ATMPs: Introduction

• Overview on Products and Therapies: Reality and Future
• Legal Framework in EU and Germany
• CTA, Hospital Exemption and Marketing Authorisation: Steps to Consider in the Development of ATMPs

The New EU-GMP Guideline for ATMP (Part I)

• Guideline Overview
• ATMPs & Quality Risk Management
• Zone-Concept for ATMP Facility
• Focus: Qualification & Monitoring

The New EU-GMP Guideline for ATMP (Part II)

• Focus: Process-Validation & Media Fill
• Focus: Documentation
• How to certify/release an ATMP Batch
• Specific Products/Processes

GMP for ATMP – Considerations to European and US Requirements from industrial point of view

• Essential Effects of the New Guideline
• Challenges in Practice
• US Requirements

Regulatory and Practical Aspects for ATMPs - requirements for QPs

• Starting materials for ATMPs
• Raw/ancillary materials for production
• Specifics for process validation and quality control of ATMPs
• Responsibilities of the QP - what is different for ATMPs

Requirements on Manufacturing of Cell-based products under GMP

• Important Aspects for Characterisation and Control
• Quality of Reagents and Materials
• Relevant guidance documents
• Inspection Experiences and Findings
• Common Deficiencies in Clinical Trial Applications

Case Study – Manufacture of an ATMP for a phase I/II clinical trial in an academic setting

• Installation of a clean room facility for manufacture of ATMPs in an academic setting
• Establishment and validation of the manufacturing process with special focus on GMP-compliant FACS sorting
• Application for a phase I/II investigator initiated clinical trial

GMP Implementation - Practical Industrial Experiences

• Challenges in aseptic manufacturing
• Dealing with research grade raw materials in a cGMP environment
• Dealing with Contract Manufacturing organisations
• Specific cGMP challenges and possible solutions

Microbiological Safety of ATMPs

• Challenges and Critical Aspects
• Relevant Guidance Documents
• Modern Microbiological Safety Concepts
• Case Studies from Microbiological Assessment