Why Quality Culture Matters

The Importance of Quality Culture

Quality Culture is an extremely important concept in pharmaceutical manufacturing facilities. In recent years, the importance of fostering a quality culture has been explicitly required in the PIC/S (Pharmaceutical Inspection Co-operation Scheme) Data Integrity Guidance and the ICH Q10 (Pharmaceutical Quality System) guideline.

The Critical Nature of Pharmaceuticals

The pharmaceuticals manufactured in pharmaceutical facilities are products directly connected to people’s lives and health. It is essential to keep in mind that a single product can significantly influence one patient’s life.

Definition of Quality Culture

Quality Culture means not just aiming to manufacture products according to specifications, but creating an organizational atmosphere where “quality is the top priority.” This means that all employees are aware of their responsibility for quality and act with an attitude of always pursuing the best, not merely following procedures and rules.

The PIC/S Data Integrity Guidance (revised in 2021) defines quality culture as “the collection of values, beliefs, thinking, and behaviors demonstrated consistently by management, team leaders, quality personnel, and all personnel that contribute to creating a quality culture to assure data quality and integrity.”

Moving Beyond Blind Compliance

So-called Blind Compliance is problematic. This refers to a state where work is performed merely for the purpose of following rules, without understanding why those rules exist or what purpose they serve. The problem with Blind Compliance is that it leads to GMP compliance aimed only at avoiding findings during inspections and audits, lacking scientific rationale and risk-based judgment.

ICH Q10 (issued in 2008, notified in Japan in 2010) aims to improve such situations and establish a quality management system capable of identifying and continuously improving issues. ICH Q10 emphasizes important concepts such as continuous improvement, management responsibility, risk management, and knowledge management, highlighting a science and risk-based approach.

Not Overlooking Small Abnormalities

For example, suppose someone notices a slight deviation in machine settings on a production line. That deviation may not immediately cause a problem. However, if left unaddressed, it could combine with other issues to create a serious defect. Detecting such small abnormalities and risks early and responding promptly is an important part of quality culture. While this response may temporarily reduce production efficiency, it enhances product reliability in the long term and protects patient safety.

The Attitude of Companies with Established Quality Culture

In companies where quality culture is established, each employee understands “why this procedure is important” and approaches their work by deeply considering its meaning, rather than merely repeating tasks.

For instance, even with cleaning work, rather than simply following instructions, employees understand how that cleaning affects product safety and act to always seek the best results. Such attitudes ultimately lead to product safety and trust from patients.

The Importance of Communication

Quality culture is also deeply related to communication in the workplace. The PIC/S Guidance states that management should “create a work environment (i.e., quality culture) that is transparent and open, one in which personnel are encouraged to freely communicate failures and mistakes, including potential data reliability issues, so that corrective and preventive actions can be taken.”

When problems are discovered, rather than hiding them or ignoring them through self-judgment, an environment is required where reporting to team members and supervisors is encouraged. By sharing problems and solving them as a team, employees can avoid isolation and support each other while maintaining a sense of responsibility for quality. In an environment where quality culture is established, making mistakes is not feared; instead, learning from mistakes and making improvements is encouraged.

Management is required to implement fair and just outcomes and rewards that promote good cultural attitudes to ensure data integrity.

Historical Lessons in Pharmaceutical Quality Control

When considering the importance of pharmaceutical quality control, the Thalidomide tragedy that occurred from the late 1950s to the early 1960s comes to mind.

Overview of the Thalidomide Tragedy

Thalidomide was launched in 1957 in former West Germany as a sedative-hypnotic drug under the brand name “Contergan.” In Japan, it was released in January 1958 as “Isomin,” and later in 1960, it was also formulated in the gastrointestinal drug “Provan M.” This drug was marketed as a “safe sleeping pill” and was widely used, especially as a remedy for morning sickness in pregnant women.

However, around 1960, there was a rapid increase in newborns with congenital malformations, such as limb deficiencies, which had previously been rarely seen in Germany. In November 1961, Dr. Lenz of Germany warned of the causal relationship between thalidomide and malformations (Lenz Warning), and sales were immediately halted in European countries. In contrast, in Japan, sales continued until September 1962, and this delay in response led to an expansion of the damage.

It is estimated that between several thousand to 10,000 fetuses worldwide, and approximately 1,000 (including stillbirths) in Japan, were affected. In Japan, 309 surviving victims have been recognized.

Impact of the Thalidomide Tragedy on Pharmaceutical Regulations

This tragedy became an event that made the world aware of the importance of ensuring pharmaceutical safety. The thalidomide tragedy triggered major changes in pharmaceutical regulations.

In the United States, the Kefauver-Harris Amendment of 1962 made it necessary to demonstrate efficacy through “adequate and well-controlled studies” for drug approval. Japan similarly revised its Pharmaceutical Affairs Law in 1967, introducing the same requirements. Additionally, Good Laboratory Practice (GLP) was established in 1978, creating standards to ensure the reliability of safety in clinical trials.

Notably, in the United States, FDA reviewer Frances Kelsey refused to approve thalidomide because there was no data on its effects on the fetus, protecting the American people from this drug disaster. This is an excellent example of the importance of cautious review based on scientific evidence.

It is essential to cultivate a quality culture without forgetting such lessons from the past.

Pharmaceutical Quality and Patient Safety

Furthermore, for example, when a diabetic patient uses insulin injections daily, the quality of that product directly affects the patient’s life. If the product’s effectiveness is unstable, blood sugar control becomes difficult, potentially leading to serious health problems. In this way, pharmaceutical quality is non-negotiable.

Building Quality Culture Through Daily Actions

Quality culture is built through small daily actions.

Even when filling in manufacturing records, it is important to have the awareness not just to copy down numbers, but to check whether those values are within the appropriate range. This is not just data entry but an important opportunity to verify product quality.

Also, even with cleaning work, rather than just cleaning designated places as instructed, when unusual dirt is found, considering its cause and reporting it can lead to early detection of potential problems.

Practices for Fostering Quality Culture

In recent years, various initiatives to foster quality culture have been implemented in the Japanese pharmaceutical industry. For example, the following measures are being carried out:

Initiative Category	Specific Examples
Management Commitment	Messages from top management regarding quality, clarification and dissemination of quality policies
Communication Environment	Open door systems (setting times when plant managers can freely talk with anyone), anonymous suggestion and question systems
Education and Awareness	Education including the “why” of work procedures, providing opportunities to understand patients’ daily lives and their thoughts about pharmaceuticals
Evaluation and Recognition	Employee recognition systems, quantitative evaluation through quality metrics
System Improvement	Building systems to ensure data integrity, implementing risk management

Through these initiatives, it is important to promote individual behavioral changes and foster quality culture throughout the organization.

The Essence of Quality Culture

Quality culture begins with compliance with rules and procedures, but true quality culture is built by understanding “why it is necessary” beyond that and acting on one’s own thinking.

Establishing quality culture is not achieved overnight. However, by all employees maintaining high awareness of each action and prioritizing quality first, a solid quality culture can be built.

As ICH Q10 indicates, the pharmaceutical quality system has three main objectives: product realization, maintenance of a state of control, and continuous improvement. To achieve these objectives, the awareness and behavior of the people operating the system—that is, quality culture—are extremely important.

The accumulation of steps starting today shapes the culture of the entire organization and ultimately leads to patient safety and trust. This is the answer to the question of why quality culture is important.

Latest Regulatory Trends

In 2014, Japan officially joined PIC/S, advancing alignment with international pharmaceutical manufacturing and quality control standards. In 2016, PIC/S and FDA issued guidance on data integrity, further emphasizing the importance of quality culture.

Within Japan, serious cases have occurred that are considered to be caused by a lack of quality culture, such as the Kobayashi Kako incident (2020-2021) and Nichi-Iko’s quality problems. These cases demonstrate that simply following procedures is insufficient and that reform of the organization’s overall culture and climate is necessary.

The 2019 revision of the Pharmaceuticals and Medical Devices Act mandated the establishment of a responsible officer at marketing authorization holders, further clarifying management’s responsibility for quality. This reflects the importance of “management responsibility” required by ICH Q10 in Japanese regulations.

Fostering quality culture is a challenge for the entire pharmaceutical industry and requires continuous effort.