What is State of the Art?
“State-of-the-art” refers to the most advanced technology or best practices currently available, representing “the best available technical and scientific knowledge at a given time” as expected by regulatory authorities. This concept extends far beyond merely introducing the latest equipment; it encompasses a comprehensive approach to continuous quality improvement and enhanced product safety.
Historical Delays in Adoption and the Changing Landscape
Pharmaceutical and medical device companies have historically lagged behind other industries in adopting automation systems and IT technologies. The primary barrier has been stringent regulatory requirements, particularly validation requirements. However, the landscape is changing significantly with the May 2025 amendment to Japan’s Pharmaceutical and Medical Device Act (PMD Act) and the progression of international regulatory harmonization.
The 2025 PMD Act amendments include strengthening quality and safety assurance for pharmaceuticals and medical devices, reinforcing stable supply systems for medical products, creating an environment conducive to active drug discovery, and enhancing pharmacy functions. Notably, the frequency of GMP compliance inspections has been changed from every five years to every three years, reflecting the increased emphasis on continuous quality assurance systems.
The Essential Meaning of State of the Art
State-of-the-art is not merely about the latest equipment and systems. Regulatory authorities expect companies to continuously incorporate the latest information to improve quality systems and regularly review product design, manufacturing processes, and risk analysis.
Knowledge Encompassed by State of the Art
Information that pharmaceutical and medical device companies should monitor and integrate into their processes includes:
Latest Regulatory Requirements
- Current regulatory requirements (PMD Act, GMP regulations, QMS regulations, etc.)
- International regulatory harmonization trends (ICH, IMDRF, etc.)
- New approval systems such as two-stage approval and conditional early approval systems
Latest International Standards
- ISO 13485:2016 (Medical devices – Quality management systems) – confirmed in 2020, next review scheduled for 2026
- ISO 14971:2019 (Medical devices – Application of risk management) – confirmed in March 2025, next review in five years
- IEC 62304 (Medical device software – Software life cycle processes) – 2nd edition under development, including AI compliance
- ICH Q8 (Pharmaceutical Development), Q9 (Quality Risk Management), Q10 (Pharmaceutical Quality System)
- ISO 9001:2015 (Quality management systems)
Safety Information
- Latest safety information (adverse events, malfunction reports, incident reports, etc.)
- Post-market surveillance data and real-world evidence
- Reports of suspected adverse reactions and malfunctions
Competitor Information and Industry Trends
- Recall reports and voluntary improvement reports by marketing authorization holders
- Industry-wide quality issues and lessons learned
- Competitor best practices
Clinical and Treatment Methods
- Latest treatment methods (alternative therapies, alternative technologies, etc.)
- Accumulation of clinical evidence
- Changes in patient needs
Technology and Manufacturing Techniques
- Latest technologies (facilities and equipment, analytical instruments, software as medical devices, etc.)
- Manufacturing process improvement technologies
- Digitalization and smart manufacturing technologies (DX, AI utilization, etc.)
- Process Analytical Technology (PAT)
Current Challenges
Once development is complete and manufacturing begins, companies rarely fundamentally review their design (process design), manufacturing, or risk analysis. However, there is a critical need to continuously incorporate:
- Better manufacturing methods and quality control techniques
- Lessons learned from competitor failures
- Newly identified risks and hazards
- Changes or additions to regulatory requirements
- Improvement opportunities arising from technological innovation
International Regulatory Trends
US FDA
Effective February 2, 2026, the FDA will transition from the Quality System Regulation (QSR) to the new Quality Management System Regulation (QMSR), which is fully harmonized with ISO 13485:2016. This will further strengthen alignment with international quality standards.
EU MDR/IVDR
The EU Medical Device Regulation (MDR) and In Vitro Diagnostic Regulation (IVDR) explicitly require the state-of-the-art concept, mandating manufacturers to implement risk management and quality assurance based on the latest technical standards.
Japan
The 2025 PMD Act amendments advance institutional arrangements aimed at balancing innovation and quality assurance, including the introduction of a two-stage approval system for software as medical devices, accelerated review for orphan drugs and devices, and promotion of manufacturing process informatization.
Position within Quality Management Systems
Requirements under ISO 13485
ISO 13485:2016 requires documentation of risk management processes in product realization. Organizations must:
- Demonstrate compliance with applicable regulatory requirements
- Implement and maintain the quality management system
- Conduct risk management throughout the product lifecycle
- Engage in continuous quality improvement activities
Risk Management under ISO 14971
ISO 14971:2019 is the international standard for medical device risk management, covering:
- Development of risk management plans
- Hazard identification (device, use, environment, foreseeable misuse)
- Risk evaluation (probability and severity)
- Risk control measures
- Residual risk evaluation and benefit-risk analysis
- Feedback of post-market information into risk files
Quality Risk Management under ICH Q9/Q10
In the pharmaceutical field, ICH Q9 (Quality Risk Management) and ICH Q10 (Pharmaceutical Quality System) provide a systematic risk management approach throughout the product lifecycle. They emphasize:
- Science-based decision making
- Risk-based thinking and actions
- Consistent quality systems from product development through manufacturing to post-marketing
- Continuous improvement and knowledge management
Future Outlook
In the future, how companies monitor state-of-the-art and feed it back into their processes will become a critical evaluation point in regulatory inspections and audits. Specifically, the following will be required:
Establishment of Systematic Information Collection Systems
- Regular collection and evaluation of regulatory, safety, and technical information
- Benchmarking of industry trends and competitor cases
- Tracking of international standards revision trends
Integration into Processes
- Reflection of collected information in product development and manufacturing processes
- Regular review and update of risk management files
- Consideration of state-of-the-art in change management processes
Cultivation of Organizational Culture
- Top management commitment
- Establishment and maintenance of quality culture
- Implementation of continuous education and training
Utilization of Digital Technologies
- Informatization of manufacturing and testing processes (also promoted in the 2025 PMD Act amendments)
- Advanced quality control utilizing AI and DX
- Real-time data utilization and implementation of Process Analytical Technology (PAT)
Summary
State-of-the-art is not merely about introducing the latest technology but represents a comprehensive approach to continuous quality improvement and ensuring patient safety. As regulatory requirements strengthen and international harmonization progresses, companies are required to:
- Establish systems to continuously monitor the latest regulatory requirements, international standards, and safety information
- Build mechanisms to systematically reflect collected information in product design, manufacturing processes, and risk analysis
- Foster a consistent quality culture from top management to the shop floor
- Construct efficient and effective quality management systems utilizing digital technologies
By implementing these practices, companies can not only ensure compliance with regulatory requirements but also achieve continuous improvement in product quality and maximization of patient safety. Engagement with state-of-the-art is no longer optional but has become an essential requirement for maintaining competitiveness in the global market.
Reference Table: Key International Standards and Guidelines (as of January 2026)
| Standard/Guideline | Current Version | Latest Status | Next Review | Key Focus Areas |
|---|---|---|---|---|
| ISO 13485 | 2016 | Confirmed 2020 | 2026 | Medical device QMS, regulatory compliance |
| ISO 14971 | 2019 | Confirmed Mar 2025 | 2030 | Risk management throughout product lifecycle |
| IEC 62304 | 2006 + A1:2015 | 2nd ed. in development | TBD | Software lifecycle, AI integration |
| ISO 9001 | 2015 | Current | 2025-2026 | General QMS framework |
| ICH Q8 | R2 (2009) | Current | Ongoing | Pharmaceutical development, design space |
| ICH Q9 | R1 (2023) | Current | Ongoing | Quality risk management |
| ICH Q10 | 2008 | Current | Ongoing | Pharmaceutical quality system |
| FDA QMSR | – | Effective Feb 2026 | – | Harmonized with ISO 13485:2016 |
Reference Table: State-of-the-Art Information Sources and Monitoring Frequency
| Information Category | Primary Sources | Recommended Monitoring Frequency | Integration Point in QMS |
|---|---|---|---|
| Regulatory Requirements | PMDA, FDA, EMA, MHLW websites | Monthly | Management review, change control |
| International Standards | ISO, IEC, ICH websites | Quarterly | QMS procedures, risk management |
| Safety Information | PMDA databases, MAUDE, EUDAMED | Weekly | CAPA, risk management file updates |
| Competitor Recalls | Regulatory authority databases | Weekly | Risk analysis, design review |
| Clinical Evidence | Medical journals, conferences | Quarterly | Product development, clinical evaluation |
| Manufacturing Technology | Industry publications, trade shows | Semi-annually | Process improvement, technology assessment |
| Industry Best Practices | Professional associations, benchmarking | Annually | Strategic planning, quality objectives |
This systematic approach ensures that state-of-the-art considerations are embedded throughout the organization’s quality management system and continuously inform decision-making at all levels.
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