Chemistry, Manufacture and Control (CMC) - Regulatory Requirements for Biological Drug Products Training Course

Welcome and Introductions

Understanding Biologics

• Understanding what a Biological Product is
• Defining ATMPs
• The difference between small and large molecules

CMC Regulatory Guidelines for Biological Drug Products - Part 1

• Relevant laws, main guidelines & monographs, specifically for biologics (i.e. ATMP guideline and other relevant guidelines for mRNA products)
• ICH guidelines specific to different modalities (i.e. recombinant proteins, ATMP0
  • Brief background on ICH (e.g., countries belonging to ICH, full membership, observers etc.)
  • Q1-Q6B (no focus on New Chemical Entities (NCEs))                       
  • Q7-Q12 (requirements due to Q12 revision)  

CMC Regulatory Guidelines for Biological Drug Products - Part 2 (continued)

Understanding the Key CMC Aspects of the Common Technical Document (CTD) - Part 1

• Quality Overall Summary (QOS)                       
• Examining the structure and content of the CMC sections – developing a CTD Roadmap
• Overview of the Drug Substance Sections for biologics                          
• Examine the linkage to the Drug Product Section                        
• Examine some basic rules for Q11 development and manufacture of drug substances 
• Significant differences between EU & US & JP (e.g. P.3.5 FDA expectation)      

Understanding the Key CMC Aspects of the CTD - Part 2 (continued)

CMC Regulatory Requirements During Differenct Stages of Development - Part 1

• Understand the definition and requirements at different stages of development (early stage, linked to clinical trials) as well as for different modalities (mRNA vs. Cell and gene)                       
  • QbD elements: QTPP, CQA, Process Characterization and Validation, Control Strategy
  • Starting materials: MCB and WCB (monoclonality, characterization, follow-up batch qualification)

CMC Regulatory Requirements During Different Stages of Development - Part 2 (continued)

• Potency assay: development, inter-assay comparability, critical reagent           
• Reference standard: Primary & working standard (re- & follow-up qualification)
• Stability requirements & resulting concept (accelerated development): development batch, technical batch, pre-validation batch, PPQ batches                          
• Comparability exercise for biologics according to ICH Q5E
  • Extended characterization: early versus late phase development
  • Orthogonal methods

CMC Regulatory Requirements During Different Stages of Development - Part 3 (continued)

• The Review dimensions of the dossier
• Clinical stages and linkage to formulation / analytical development
• Develop strategies to overcome challenges             

Building the Pharmacuetical Sections of the Dossier

• Examining the importance of development biologics/ATMPs                       
• Review of the sections on development biologics/ATMPs (P2 and S26)           
• Understanding the reviewer’s perspective, highlighting methods to ensure we answer the reviewer’s questions                       

Understanding Source Documents

• Overview of source documents                       
• Understanding the reviewer’s perspective (Using analytical data as an example)
• Highlight the needs of internal teams versus external reviewers                       
• Reviewer's questions to be answered

Change Control for Biological Products

• Change control and the impact of your dossier
• The importance of comparability                       
• Practical exercise on change control