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ADVANCED LEVEL

Process Validation for Biotechnological Products

In-House Training

TRAINING OVERVIEW

Manufacturing processes should be validated prior to initiate commercial manufacturing. Regulatory bodies expect that the manufacturer understand the process so that quality, safety and efficacy of the product are designed or built into the product through the appropriate control of each manufacturing process steps. Today, process validation comprises three main steps: (1) Stage 1 – Process Design (FDA) or Process Evaluation (EMA); (2) Stage 2 – Process Qualification (FDA) or Process Verification (EMA); and (3) Continued Process Verification (FDA) or On-going Process Verification (EMA). The training aims to provide deeper understanding on how process validation for biotechnological processes, which is the collection and evaluation of data from the process design stage through commercial production, would be appropriately designed and executed to establish scientific evidence that a manufacturing process is capable of consistently delivering quality product.

• Understand how to qualify scale-down models, to assess the criticality of quality attributes (CQAs), material attributes (CMAs) and process parameters (CPPs).

• Propose methods to build up process characterization studies looking at interactions between CQAs/CMAs and CPPs and determining the acceptable ranges of process parameters to deliver quality product.

• Learn how to perform clearance of impurities, worst-case studies and excursion studies

• Understand how to set-up a control strategy.

• Learn on the qualification of cell banks.

• Understand how to assess microbiological risks (including viruses) during manufacturing, toxicological risks related to raw materials, extractables/leachables from consumables and elemental impurities.

• Learn how to perform viral clearance studies, mixing studies, resin and membrane lifetime studies, homogeneity and uniformity studies, freeze-thaw studies, shipment qualification studies, reprocessing studies, container closure integrity testing and validation of sterile filtration.

• Provide guidance on the performance of stability studies related to process performance qualification.

• Understand how to determine the number of process performance qualification (PPQ) runs, how to perform PPQ and how to assess PPQ-derived data.

• Provide guidance on the purpose and design of continued process verification.

• Process development scientists and managers

• CMC development program managers

• Pharmaceutical development scientists and managers

• Manufacturing managers

• QC and stability control managers

• Heads of Quality Assurance

• Drug Regulatory Affairs managers

AGENDA

Introduction

  • Overview of Process Validation in accordance with EMA and FDA’s guidelines as well as ICH Q8(R2) and ICH Q11

  • Validation Master Plan (VMP)

  • TPP and QTPP

Stage 1 - Process Design (DS &DP)

  • Assessment of criticality of quality attributes (cQAs)

  • Structure-function relationship studies

  • Assessment of criticality of material attributes (CMAs)

  • Assessment of criticality of process parameters (CPPs)

  • Qualification of scale-down model (SDM)

  • Process characterization studies

  • Design space and Monte Carlo simulations

  • Worst case and excursion studies

  • Clearance of impurities

  • Deliverables – Process Control Strategy

  • ICH Q12 - Established Conditions (ECs)

Stage 2 - DS & DP Process Performance Qualification (PPQ)

  • Facility Qualification and Process Performance Qualification

  • Number of PPQ batches

  • Stability of Process Solutions and Samples

  • Process Intermediates Hold Times

  • Cumulated Hold Times

  • Assessment of PPQ campaign

Stage 3 - Continued Process Verifiaction (CPV)

  • State of Control

  • Process Control and Process Capability

  • Run charts and Statistics

Process Validation specificities for Continuous BioManufacturing

  • Principles

  • Sart-up/Shutdown and In-Process Disturbances

  • Residence Time Distribution (RTD)

  • Viral Clearance

  • In-line Filtering and Nanofiltration

Expedited Programs

  • What should be the CMC package content?

  • Early access to Patients

  • Regulatory Expectations

  • Flexibility

  • Concurrent Validation

  • Stability Data

Ancillary Process Validation Studies (DS and DP when appropriate)

  • Cell bank system qualification (evaluation of clonality, ICHQ5(D), Cell bank establishment and testing, EoPCB and LIVCA)

  • Viral Safety Evaluation (regulatory guidelines, cell bank safety testing, biological raw material testing, unprocess bulk testing, viral clearance studies)

  • Resin/Membrane Lifetime Studies

  • Mirobiological Control in Bioprocessing

  • Toxicological assessment of residual raw materials

  • Nitrosamines impurities

  • Extractables & Leachables

  • Elemental impurities

  • Mixing studies

Ancillary Process Validation Studies (continued)

  • Homogeneity & uniformity studies

  • Freeze-thaw studies

  • Sterility

  • Aseptic Process Simulation (Media Fill)

  • Sterile Filtration

  • Container Closure Integrity

  • Qualification of Visual Inspection

  • Forced Degradation studies

  • Stability studies

  • Photostability studies

  • Reprocessing and Reworking

  • Shipment studies

Definition of process validation terms

Questions & answers

Interested in this course?

Please contact us at mylene.talabardon@biotechnologyconsultant.com