Understanding Quality Systems

Introduction to Quality Systems

In the medical device industry, the construction of a quality system has been required under ISO 13485 and the QMS Ministerial Ordinance (QMS省令).

Meanwhile, the revised GMP Ministerial Ordinance (改正GMP省令) that came into effect on August 1, 2021, also mandates the establishment of a Pharmaceutical Quality System (PQS) for pharmaceutical manufacturers. This marked a significant shift in pharmaceutical quality assurance requirements in Japan.

Definition and Fundamentals

A Quality System (QS) is also referred to as a Quality Management System (QMS). The fundamental basis of any quality system is the PDCA cycle (Plan-Do-Check-Act).

The existence of a PDCA cycle means that there is a “mechanism” or “system” in place where quality improves progressively—better today than yesterday, better tomorrow than today. This continuous improvement philosophy is at the heart of modern quality management.

In a quality system, “mechanisms” for managing and improving quality, as well as “mechanisms” for ensuring quality, are established through documented procedures known as Standard Operating Procedures (SOPs). These documented procedures form the backbone of organizational knowledge and ensure consistency across operations.

Additionally, Quality Risk Management (QRM) similarly incorporates the PDCA cycle and forms an integral relationship with the quality system. By combining the quality system with quality risk management, organizations can manage product quality, ensure product quality assurance, and reduce product risks to acceptable levels. This integrated approach represents modern best practices in regulated industries.

Quality Management Systems in ISO 9001

ISO 9001:2015, the quality management standard, illustrates the PDCA model through a process-based approach with the following structure:

Context of the Organization and Leadership → Planning (Plan) → Support and Operation (Do) → Performance Evaluation (Check) → Improvement (Action)

Planning Phase (Plan)

In the planning process, management creates a quality policy and establishes quality objectives on an annual basis. Quality objectives must be achievable and clearly defined with specific numerical targets and achievement criteria. Examples include:

• Reducing customer complaints by 3 points
• Decreasing deviations by 5 points
• Increasing customer satisfaction by 10 points

Furthermore, management must allocate appropriate resources (people, materials, and financial resources). Without preparing resources and merely providing verbal instructions, quality improvement cannot be executed effectively. Resource allocation may include hiring personnel, implementing training programs, or engaging consultants to build organizational capability.

Support and Operation Phase (Do)

In the support and operation process (product realization process), research, development, design, manufacturing, distribution, and services are implemented in accordance with the QMS. The objective is to ship products to the market that meet user needs and requirements, thereby achieving customer satisfaction.

For this purpose, employee competence is crucial. Competence encompasses not only technical skills but also the ability to understand and apply quality principles in daily work. Organizations must invest in continuous training and development to maintain and enhance workforce competence.

Performance Evaluation Phase (Check)

In the performance evaluation process, the status of products and processes is monitored and measured. Products include raw materials, intermediates, semi-finished products, finished products, and services.

Products are measured through various inspections—incoming inspection, in-process inspection, and final inspection—to verify whether they meet design quality specifications. During manufacturing, process parameters such as temperature, humidity, particulate matter (dust), differential pressure, and torque are measured to ensure process control and capability.

Internal audits are also conducted to proactively discover latent problems (i.e., risks). Internal audits are referred to as “Self Inspection” (自主的な査察). Although the Japanese regulations translate this as “自己点検” (self-inspection), this terminology is not entirely appropriate as it may understate the rigor required.

In Self Inspection, it is important for companies to discover risks daily through their own internal audits and to implement corrective and preventive actions. In other words, rather than waiting for regulatory authority inspections to identify issues, companies should proactively implement improvement activities themselves. This proactive approach demonstrates organizational maturity and commitment to quality.

The results of corrective and preventive actions (CAPA) and internal audits are fed back to the management process. Management then issues improvement directives through management reviews and establishes quality objectives for the following year.

Furthermore, management must periodically conduct management reviews and provide appropriate instructions for quality improvement. Management review is a critical mechanism for ensuring that the quality system remains effective, suitable, and aligned with organizational objectives.

Improvement Phase (Action)

In the improvement process, customer complaints and other quality data are collected, and corrective and preventive actions are taken to prevent recurrence. The critical aspect of corrective action is investigating the root cause of problems and eliminating them to prevent recurrence. It is important to note that correction and corrective action are different concepts—correction addresses the immediate symptom, while corrective action addresses the underlying cause.

Improvement must not be a one-time event. Through continuous improvement, organizations must meet regulatory requirements and customer requirements on an ongoing basis. This commitment to continuous improvement should be embedded in the organizational culture.

Example of PDCA Cycle in Quality Systems

The PDCA cycle operates continuously throughout the organization:

Phase	Key Activities	Outcomes
Plan	• Set quality policy and objectives• Allocate resources• Identify risks and opportunities	• Documented quality objectives• Resource allocation plan• Risk management plan
Do	• Execute processes according to procedures• Train personnel• Manufacture products	• Trained workforce• Products meeting specifications• Process records
Check	• Monitor and measure processes• Conduct internal audits• Perform management review	• Performance data• Audit findings• Management review records
Act	• Implement CAPA• Update procedures• Plan improvements	• Improved processes• Updated documentation• Reduced nonconformities

FDA Quality System Inspections

As pharmaceutical and medical device companies promote globalization, they increasingly face inspections by overseas regulatory authorities such as the FDA. Conversely, regulatory authorities are increasing the number of overseas inspections in response to the globalization of supply chains.

However, since resources available for inspections are limited, efficient inspection methodologies are necessary. In traditional inspections, if items pointed out by inspectors were corrected, they were generally accepted.

Evolution of Inspection Approaches

However, there is a fundamental limitation: during inspections lasting only a few days (in the case of FDA inspections in Japan, typically 4 or 5 days), the number of problems and risks that inspectors can discover is inherently limited. Therefore, simply correcting the errors (risks) discovered by inspectors does not necessarily ensure the safety of the citizens of that country.

Consequently, the FDA and other regulatory authorities have shifted from an inspection methodology that discovers errors (risks) to a methodology that investigates whether a company has established a “Quality System” under the governance of management. This paradigm shift represents a move from reactive compliance to proactive quality culture assessment.

Medical Device Inspections

For medical device companies, the FDA conducts quality system inspections in accordance with the Quality System Regulation (QSR, 21 CFR Part 820) using the Quality System Inspection Technique (QSIT). Important Update: As of February 2, 2026, the QSIT will be withdrawn and replaced with a new inspection process aligned with the Quality Management System Regulation (QMSR), which harmonizes U.S. requirements with ISO 13485:2016.

Pharmaceutical System-Based Inspections

For pharmaceutical companies, the FDA classifies manufacturing site activities into the following six systems and conducts systematic inspections called “system-based inspections”:

1. Quality System – The foundation of all other systems
2. Facilities and Equipment System – Infrastructure and maintenance
3. Materials System – Supply chain and material control
4. Production System – Manufacturing operations and controls
5. Packaging and Labeling System – Final product presentation
6. Laboratory Control System – Analytical testing and release

There are two types of system-based inspections: comprehensive inspections and abbreviated inspections.

Comprehensive Inspections:

• A minimum of 4 systems out of 6 are selected
• The Quality System is mandatory
• Conducted when: GMP status is unknown, major changes have occurred, or serious complaints or quality issues have arisen

Abbreviated Inspections:

• A minimum of 2 systems out of 6 are selected
• Like comprehensive inspections, the Quality System is mandatory
• Conducted for lower-risk scenarios or routine surveillance

The Importance of Self-Inspection

In FDA and other regulatory authority inspections, the goal is to confirm that companies have established their own Quality System (QS) and that, even without inspections, they implement identification and improvement activities at the same level as inspectors would (Self Inspection). This self-regulation capability is the hallmark of mature quality organizations.

For this purpose, securing excellent audit personnel is of paramount importance. A company with an established Quality System is one that inspectors can trust and have confidence in. Such companies demonstrate:

• Proactive risk identification and mitigation
• Robust CAPA systems with root cause analysis
• Management commitment and oversight
• Continuous improvement culture
• Comprehensive documentation and traceability

Recent Regulatory Developments

Japan’s GMP Reform (2021)

The 2021 revision of Japan’s GMP Ministerial Ordinance introduced several critical updates:

• Pharmaceutical Quality System (PQS): Mandatory establishment aligned with ICH Q10 guidelines
• Data Integrity: Explicit requirements for electronic data management and security
• Management Responsibility: Enhanced requirements for senior leadership involvement
• Risk-Based Approach: Integration of ICH Q9 quality risk management principles
• Supplier Management: Strengthened requirements for supply chain oversight

ISO 13485 Updates

ISO 13485:2016 remains the current version as of 2025, having undergone systematic review in 2020. This medical device quality management system standard continues to serve as the foundation for:

• European Union MDR (Medical Device Regulation) and IVDR (In Vitro Diagnostic Regulation) compliance
• Canadian MDSAP (Medical Device Single Audit Program) requirements
• Japanese QMS Ministerial Ordinance alignment
• U.S. FDA QMSR (Quality Management System Regulation) effective February 2, 2026

The alignment of global medical device regulations around ISO 13485 represents a significant step toward international harmonization and reduced regulatory burden for manufacturers operating in multiple markets.

FDA Quality Management System Regulation (QMSR)

In January 2024, the FDA published the final rule establishing the QMSR to replace the QSR. Key changes include:

• Harmonization with ISO 13485:2016: The QMSR closely aligns with international standards while maintaining specific U.S. requirements
• Management Review Transparency: Removal of exemptions for management reviews, quality audits, and supplier audit reports from inspection
• Enhanced CAPA Requirements: More specific requirements for when issues must be elevated to CAPA
• New Inspection Approach: Transition from QSIT to a revised inspection process (effective February 2, 2026)

Best Practices for Quality System Implementation

Building a Robust Quality Culture

A successful quality system requires more than documentation and procedures. Organizations must cultivate a quality culture characterized by:

Leadership Commitment:

• Visible and active support from senior management
• Adequate resource allocation
• Regular engagement in quality reviews
• Setting the tone for quality throughout the organization

Employee Engagement:

• Comprehensive training programs
• Clear communication of quality expectations
• Empowerment to identify and address quality issues
• Recognition of quality contributions

Continuous Improvement Mindset:

• Regular analysis of quality metrics and trends
• Proactive identification of improvement opportunities
• Implementation of lessons learned
• Sharing best practices across the organization

Integration of Risk Management

Quality Risk Management should be integrated throughout the product lifecycle:

Lifecycle Stage	Risk Management Activities
Development	• Identify potential quality attributes• Assess development risks• Define control strategies
Manufacturing	• Monitor critical process parameters• Validate control effectiveness• Manage supply chain risks
Post-Market	• Analyze customer complaints• Monitor product performance• Evaluate emerging risks

Technology and Digital Transformation

Modern quality systems increasingly leverage technology:

• Electronic Quality Management Systems (eQMS): Centralized platforms for document control, CAPA, change control, and training management
• Data Analytics: Real-time monitoring and trending of quality metrics
• Artificial Intelligence: Predictive analytics for risk identification and preventive action
• Blockchain: Enhanced traceability and data integrity in supply chains

Preparation for Regulatory Inspections

Pre-Inspection Readiness

Organizations should maintain inspection readiness through:

Documentation Excellence:

• Up-to-date procedures reflecting actual practices
• Complete and accurate records
• Readily accessible documentation
• Clear traceability throughout systems

Mock Inspections:

• Regular internal audits using regulatory inspection approaches
• Cross-functional mock inspections
• Third-party audit preparation exercises
• Documentation of findings and corrective actions

Personnel Preparedness:

• Training on inspection protocols and expectations
• Role-playing inspection scenarios
• Clear understanding of responsibilities during inspections
• Designated inspection coordination team

During Inspection

Best Practices:

• Provide a designated workspace for inspectors
• Respond promptly and accurately to information requests
• Maintain professional and cooperative attitude
• Take detailed notes of discussions and observations
• Understand the difference between observations and objections
• Seek clarification when inspector comments are unclear

Response Strategy:

• Have subject matter experts available
• Provide context for observations without being defensive
• Acknowledge legitimate concerns promptly
• Document commitments made during inspection
• Prepare for closing meeting discussion

Post-Inspection Follow-up

Effective CAPA:

• Thorough root cause analysis using structured methodologies (5 Whys, Fishbone diagrams, etc.)
• Comprehensive corrective actions addressing system issues, not just symptoms
• Preventive actions to avoid similar issues in other areas
• Verification of effectiveness through monitoring and measurement
• Documentation of all activities with clear timelines

Global Harmonization Efforts

PIC/S (Pharmaceutical Inspection Co-operation Scheme)

As of 2025, PIC/S includes 58 regulatory authorities from 52 countries, promoting:

• Harmonized GMP requirements
• Mutual recognition of inspections
• Information exchange between authorities
• Training and development of inspectors

ICH (International Council for Harmonisation)

ICH guidelines relevant to quality systems:

• ICH Q8: Pharmaceutical Development
• ICH Q9: Quality Risk Management
• ICH Q10: Pharmaceutical Quality System
• ICH Q12: Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management

MDSAP (Medical Device Single Audit Program)

MDSAP allows a single audit to satisfy requirements of multiple regulatory authorities:

• United States (FDA)
• Canada (Health Canada)
• Brazil (ANVISA)
• Australia (TGA)
• Japan (MHLW/PMDA)

This program significantly reduces the inspection burden on manufacturers while maintaining regulatory oversight.

Conclusion

Quality systems represent far more than regulatory compliance—they embody an organization’s commitment to delivering safe, effective, and high-quality products to patients and users. The evolution from reactive quality control to proactive quality systems, and now to integrated quality culture, reflects the maturation of regulated industries.

As regulations continue to harmonize globally around standards such as ISO 13485 and ICH Q10, manufacturers have unprecedented opportunities to streamline their quality systems while meeting multiple regulatory requirements. The key to success lies in building robust systems that go beyond minimum compliance, fostering a culture of quality, and continuously improving through the systematic application of the PDCA cycle.

Organizations that view quality systems not as a burden but as a competitive advantage—enabling them to deliver superior products, reduce risks, and operate more efficiently—will thrive in the increasingly complex global regulatory environment. The investment in quality systems today ensures the sustainability and success of pharmaceutical and medical device manufacturers tomorrow.

As we move forward, the integration of advanced technologies, enhanced data analytics, and risk-based approaches will continue to evolve quality systems, making them more efficient, more predictive, and ultimately more effective at ensuring patient safety and product quality.

Note: This document reflects regulatory requirements and industry best practices as of January 2025. Readers should consult current regulations and guidance documents from relevant regulatory authorities for the most up-to-date requirements applicable to their specific products and markets.

Key Regulatory References:

• Japan: GMP Ministerial Ordinance (令和3年8月1日施行), QMS Ministerial Ordinance
• United States: 21 CFR Part 820 (transitioning to QMSR effective February 2, 2026)
• Europe: EU MDR 2017/745, IVDR 2017/746
• International: ISO 13485:2016, ISO 9001:2015, ICH Q9, ICH Q10
• PIC/S Guide to Good Manufacturing Practice (GMP)