Combination products: From CMC and quality data to a submission-ready regulatory dossier

Key guidelines and requirements (Focus: EU)

• Medicinal products: EU GMP Volume 4, Annexes, selected ICH guidelines and more
• Medical devices: MDR/IVDR and annexes, ISO 13485/ISO 14971, roles and responsibilities, CE marking/EU Declaration of Conformity/UDI
• Combination products: MDR Article 1 and Article 117, Annex IX, borderline classification rules (Article 2 of Directive 2001/83/EC), EMA 259165/2019, EMA 37991/2019, outlook on FDA (unified approach), COMBO Group

Regulatory Affairs I: Marketing authorisation process for medicinal products

• Procedure types (national, MRP, DCP, CP)
• Application types (full dossier, generic applications)
• Marketing authorisation documentation (eCTD)
• Competent authorities
• Case study

Regulatory Affairs II: Conformity assessment of medical devices

• Medical device classification
• Roles and responsibilities (authorities, notified bodies, European Commission, etc.)
• Route selection (with or without notified body involvement)
• Technical documentation: Requirements, risk management, clinical evaluation, etc.
• QM system as an integral part of device file
• Intended use and design changes
• Case study

Documentation strategies using quality related data as a role model

• Overall concept: Regulatory vs. GMP documentation
• Identification of relevant GMP data for regulatory purposes
• Documentation principles (GDocP, ALCOA+ vs. document control)
• Roles and responsibilities
• Practical examples: Typical differences in terminology and interpretation
• Case study: From GMP to regulatory document

Combination products: Regulatory strategy

• Regulatory distinction: Medicinal products vs. medical devices
• Primary Mode of Action (PMOA): Definition, regulatory classification (EU vs. US), impact on regulatory strategy
• Intended use and PMOA: Case examples
• Regulatory strategy development
• Responsibility for placing products on the market

Bio break

Combination products: Common pitfalls and solutions

• Process thinking: Intended use vs. standardised criteria/validated processes
• Data integrity: ALCOA+ and audit trails
• Risk management: ICH Q9 vs. ISO 14971
• Supplier management and supplier risk assessment
• "Death by Change Control": The risk of product changes for combination products
• Use of computerised systems and AI (Annex 11, Annex 22)
• Lifecycle management and product maintenance
• Inspection readiness and regulatory reality
• Practical implementation of responsibility demarcation agreements

Case studies/practical workshop