Paradigm Shifts in Pharmaceutical Quality Systems
A Historical Review and Future Perspectives [Part 3]
From QC to the Pharmaceutical Quality System (PQS)
When GMP was first introduced in 1963, the “testing” conducted by the QC department played a central role. However, as GMP evolved, there was a dramatic increase in complex tasks beyond testing, such as document control, change control, and deviation management. Consequently, the FDA revised CGMP in 1978, significantly strengthening the authority of the QC department. It clarified the department’s independence from the manufacturing department and its final authority over release decisions, effectively mandating that the QC department also assume the current role of Quality Assurance (QA).
Furthermore, in 1987, the ISO 9000 Series (Quality Management Systems) was established, clearly defining the term “Quality Assurance (QA)” and spreading it worldwide. This marked the point at which QC, responsible for testing, and QA, responsible for ensuring the integrity of the entire system, became clearly distinguished. In 2008, ICH Q10 introduced the concept of a “Pharmaceutical Quality System (PQS),” which includes management responsibility. QA was redefined not merely as an on-site monitor, but as a department responsible for quality assurance at the management level.
By the way, the term “Quality Unit (QU)” was first used in ICH Q7, “Guideline on Good Manufacturing Practice for Pharmaceutical Active Substances,” published in 2000, where a QU was defined as an organization responsible for both QC and QA. Furthermore, in the FDA guidance document “Quality System Approach” published in 2006, the traditional regulatory term “Quality Control Unit” was replaced with “Quality Unit.”
Due to the historical evolution of GMP, department names vary widely: some companies have QA functions within their “QC units,” while others have “QA units” that also perform testing; in smaller factories, a single department may handle everything.
Therefore, we have decided to use the term “QU” to refer to the entire organization responsible for quality, and to emphasize that QC and QA are inseparable functions. However, please note that the U.S. CGMP (21 CFR Part 211) still uses the term “Quality Control Unit,” so please be careful not to get confused.
Around the time the concept of process validation was redefined, ICH Q10 introduced the concept of PQS. This was because incidents and supply shortages—which could not be prevented simply by manufacturing according to established procedures and shipping products only after they passed final testing—had occurred, leading to a need for management as a more comprehensive system.
With the introduction of PQS: (1) it became necessary to manage all stages—from development through manufacturing to the end of a product’s marketing—under a consistent quality policy; (2) it was explicitly stated that senior management bears ultimate responsibility for quality issues, which had previously tended to be the responsibility of the manufacturing site; and (3) there was a shift from a passive stance of following rules to an active stance of analyzing data and continuously improving on our own.
While GMP refers to “rules for producing good products on tthe manufacturing site, PQS denotes a broader framework—“a system for maintaining and improving quality across the entire company”—and incorporates GMP as part of this system, thereby contributing to pharmaceutical quality assurance.
Author
Nakao started his career in 1976 at Tanabe Seiyaku Co., Ltd. After carrying out research in synthetic organic chemistry and process chemistry (industrialization) at the company, he successively took the positions of quality assurance manager, director and general manager of production, and managing director in charge of management planning. After Tanabe merged with Mitsubishi to become Mitsubishi Tanabe Pharma Corporation, Nakao became Managing Executive Officer and Chief Director of Medicine Manufacturing. Through his experience in dealing with FDA inspections and activities at the Parenteral Drug Association (PDA), Nakao became convinced that GMP is an “exact science.”
Finding that his beliefs were reflected in CM Plus Corporation’s enthusiasm for improving GMP education, Nakao joined CM Plus in 2011 as a Director and be promoted as executive vice-president in 2012. Fellow since July 2017.
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