Understanding Quality Assurance (QA): The Importance of Process Quality Assurance

Fundamental Differences Between QA and QC

Quality Assurance (QA) and Quality Control (QC) are often confused, yet they play distinctly different roles in the pharmaceutical industry.

QC is a “reactive” activity that verifies whether manufactured products meet specifications. Specifically, it involves sampling, testing, and analyzing finished pharmaceutical products to prevent non-conforming products from reaching the market. In contrast, QA encompasses systematic activities designed to “proactively prevent” quality issues in products. This includes building quality management systems, creating Standard Operating Procedures (SOPs), process validation, auditing, and continuous improvement activities.

Aspect	QA (Quality Assurance)	QC (Quality Control)
Approach	Proactive (Preventive)	Reactive (Detective)
Focus	Process-oriented	Product-oriented
Timing	Throughout product lifecycle	Post-manufacturing inspection phase
Objective	Defect prevention	Defect detection and correction
Key Activities	Audits, process design, training, system building	Sampling, testing, inspection, analysis

Misconceptions in the Japanese Pharmaceutical Industry

In Japan’s pharmaceutical industry, there are numerous cases where QA is mistakenly understood as “Quality Audit.” In many Japanese pharmaceutical companies, it is common practice to conduct retrospective sampling audits of approved deliverables. With this method, the QA department essentially repeats the QC activities that non-audit departments have already performed.

Regarding this approach, regulatory authorities and pharmaceutical companies overseas have pointed out that Japanese QA departments are performing QC activities. Ironically, due to this duplicated checking system, data submitted by Japanese pharmaceutical companies for new drug applications are considered to be of extremely high accuracy because of the repeated verification.

However, from the perspective of international regulatory requirements, this method has a critical shortcoming: the “quality assurance of business processes themselves” is not being systematically implemented. While product quality is secured, the soundness of the processes that generate those products is not systematically assured.

True QA: The Essence of Quality Assurance

Naturally, QA means Quality Assurance. In the International Council for Harmonisation (ICH) guidelines, particularly ICH Q10 “Pharmaceutical Quality System,” the role of QA is clearly defined.

The most important aspect of QA is conducting reviews from an independent, third-party perspective at each phase of system and process planning, design, development, and operation, comparing against the following elements:

• Regulatory requirements (applicable regulations such as GMP, GCP, GLP)
• Company quality policies and objectives
• Approved procedures and protocols
• Risk assessment and management strategies
• Science-based control strategies

If audits are conducted after system completion and non-conformances are identified, it is “too little, too late.” Adding quality elements that were not incorporated during the design phase or early development is inefficient in terms of cost and time, and sometimes impossible.

Modern QA Approaches in ICH Guidelines

ICH Q9(R1): Quality Risk Management

The revised ICH Q9(R1) from 2023 emphasizes the importance of risk-based approaches. QA activities ensure product quality by scientifically evaluating potential risks and implementing appropriate control measures. Risk management facilitates continuous improvement of process performance and product quality.

ICH Q10: Pharmaceutical Quality System

ICH Q10 defines a comprehensive quality system spanning the entire product lifecycle. This guideline requires the integration of the following elements across pharmaceutical development, technology transfer, commercial manufacturing, and product discontinuation:

• Process performance and product quality monitoring systems
• Corrective Action and Preventive Action (CAPA) systems
• Change management systems
• Management review

ICH Q12: Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management

Adopted in 2019, ICH Q12 provides a framework for managing post-approval CMC (Chemistry, Manufacturing, and Controls) changes in a more predictable and efficient manner. This guideline promotes the application of Quality by Design (QbD) principles to the continuous improvement of existing products.

Quality by Design (QbD) Concept

QbD is a concept introduced in ICH Q8, aiming to build quality into the manufacturing process. Rather than assuring quality through post-manufacturing inspection, this approach builds quality in from the design stage. Through science- and risk-based development—including identification of Critical Quality Attributes (CQAs), establishment of design space, and construction of control strategies—robust and flexible manufacturing processes are established.

Practicing Process Quality Assurance

An effective QA department functions not as a “monitor” of audited departments, but as a collaborative partner. At key business milestones, process quality assurance is provided through activities such as:

1. Planning and Design Phase: Participate in project planning, risk assessment, and quality objective setting to ensure quality requirements are incorporated from the initial stage.
2. Development Phase: Review development protocols, conduct quality assessments at intermediate milestones, and monitor change management processes to detect deviations early.
3. Implementation Phase: Review validation plans, verify training implementation status, and evaluate procedure adequacy to ensure operational readiness.
4. Operational Phase: Conduct periodic audits, perform trend analysis, and support continuous improvement activities to confirm that processes maintain quality stability.

Through such a proactive QA approach, quality issues can be prevented, regulatory compliance ensured, and continuous improvement realized. Product quality is determined by the quality of the processes that create it. The QA department plays a crucial role in ensuring the soundness of these processes.

Conclusion

True Quality Assurance is not about inspecting finished products, but about assuring the processes themselves that generate high-quality products. For Japan’s pharmaceutical industry to maintain international competitiveness and continue providing safe and effective medicines to patients, it is essential to transition from a retrospective audit-centered approach to proactive process quality assurance.

As indicated by the latest guidelines such as ICH Q9(R1), Q10, and Q12, modern pharmaceutical quality systems require risk-based approaches throughout the lifecycle and science-based continuous improvement. By collaborating with audited departments and providing process quality assurance at each stage of operations, QA departments can achieve Quality Assurance in its truest sense.