The Critical Role of Management Engagement in Quality Culture

What can regulatory documents and FDA Warning Letters issued in 2021 tell regulated industries about data integrity trends? And why should industry leaders develop a data culture mindset?

During a session at the 2022 PDA Annual Meeting, Ulrich Köllisch, PhD, Manager of Data Integrity at GxP-CC, provided his analysis into data integrity trends during 2021. He discussed four regulatory documents issued in 2021 and then offered insights gleaned from two specific Warning Letters and a report by GMP Consultant Barbara W. Unger.

[Related: To access the analysis by Barbara W. Unger, click here.]

Warning Letters FY2020 and FY2021

4 Agencies Address Data Integrity

Before diving into his analysis of data integrity trends, he reviewed four data integrity guidelines issued by various agencies in 2021:

“Data is the backbone of our life science industry,” he said. “And its integrity is of imminent importance because the patient cannot on their own know whether a medication is good or bad.”

Köllisch provided an extensive analysis of the PIC/S guidance, which he characterized as addressing mostly well-known topics. The document does include what he referred to as “strong chapters” on data governance and third-party management. Other topics addressed in the document include requirements for paper-based and computerized systems. 

His “favorite” paragraph covers critical thinking.

“It explicitly states that inspectors should use critical thinking skills on the one hand, and, on the other hand, it is also an indicator of data governance, or maturity, if the organization understands and accepts procedural risks and, therefore, prioritizes it,” he said.

This ties in with management engagement, which he considers a crucial factor for quality culture.

“Management should set clear expectations and have a clear awareness,” Köllisch said. “Management must lead by example, and, very importantly, the resources have to be there in order to have a quality culture.”

[Author’s Note: For more on the link between quality culture and data integrity, read the article, “Can a Robust Quality Culture Help Prevent GMP Issues Such as Data Integrity?”]

He pointed to the document’s focus on outsourced activities as another critical area of focus. 

“We are talking here about strategies for assessing data integrity in the supply chain,” he said. “I think this is really important. Does it help me if my house is clean, but the product I get is dirty?” 

Understanding risks requires conducting regular risk reviews within the supply chain. Quality agreements should include data governance expectations for both sides.

Management should set clear expectations and have a clear awareness

“You get more security in the supply chain and your risk assessments are then up to date,” Köllisch explained. “Of course, all of this must be supported by a risk-based solid audit strategy.”

Next, he addressed the EMA guideline which he noted is the first huge data integrity guideline issued by that agency. He did not go into much detail about this document, though he said it does take into account modern clinical trial technologies such as wearables, bring-your-own-device (BYOD) applications, etc.

The WHO guidance includes GXP for medical devices, has a strong focus on data governance, and features an appendix that addresses using quality risk management (QRM) for data integrity risk management. Lastly, he said the OECD advisory document includes a “nice” definition of raw data, stating that “raw data are the results of original observations and allow complete reconstruction and evaluation of GLP activities.”

FDA Investigators Hone in on Quality Culture

Following review of the four documents, Köllisch provided his analysis of data integrity trends in 2021, including analysis of specific Warning Letters (Figure 1).

Figure 1 FDA Inspection Backlog
FIGURE 1 | FDA Drug Inspection Backlog

However, approximately 40% of Warning Letters issued in 2021 were from document requests, he explained. From this analysis, he showed that the number of Warning Letters with data integrity citations grew in spite of the reduction in onsite inspections due to the pandemic. In many cases, observations pointed to quality culture issues.

For an example of a management engagement issue, Köllisch examined a specific Warning Letter that includes insights into what FDA investigators are looking for when it comes to management engagement (Figure 2). 

Figure 2 FDA Data Integrity Trends - Quality Culture
FIGURE 2 | FDA Warning Letter Trends – Quality Culture

“I always like the response section because here you can tell us what to do,” he said, highlighting that the Warning Letter explicitly states that senior management has the inherent authority to develop and support quality culture. 

“Management engagement enables the quality culture, which can then lead to knowledge management,” he explained. “The role of management with executed responsibilities is to create a quality culture, to make the employees understand that data integrity is an organizational core. Vice versa, if you do not have it, your quality culture can break and lead to noncompliance and to quality issues, and to lack of patient safety.”

Does it help me if my house is clean, but the product I get is dirty?

Further, he explained that an intact quality culture leads to data quality. When a company has data quality, knowledge can be gained. 

“This is the point of knowledge management. When we see this value together, we can call it a ‘data culture.’”

So far this year there have been seven FDA 483 observations that pertain to data integrity. Contact us to see how you can access data integrity 483 observations by year.

2022 483 Data Integrity Observations
Redica Systems Enforcement Analytics | Data Integrity 483 Observations

FDA Expresses Data Integrity Concerns at CROs

The next Warning Letter he reviewed, from late 2020, touched on knowledge management (Figure 3).

Figure 3 FDA Data Integrity Trends Knowledge Management

“It speaks of ongoing monitoring of both intra-batch and inter-batch variation to ensure continuing state of control. That is exactly knowledge. That is statistical knowledge. I like this a lot,” he said. “The second point you can draw out of here is that the state of control should not be only during manufacturing, which the last sentence is talking about, but throughout the complete product lifecycle.” 

Addressing outsourced activities, Köllisch pointed to a notice FDA sent out in September 2021 regarding two clinical research organizations (CROs) the agency identified as “unacceptable” due to data integrity concerns.

“Of course, this has a really high impact on the pharmaceutical companies who relied on the CROs. We have to be aware that third parties like CROs, but also contract manufacturing organizations (CMOs), provide highly critical data for us,” he said. “The sponsor, or the contract giver, stays automatically responsible for ensuring that everything is okay with the data. This also goes directly back to the point from the PIC/S guideline to having a quality risk management (QRM) approach throughout the supply chain and for the service providers. This has been a blind spot throughout the past and I think we should be aware of that.” 

Ultimately, the data integrity manager wants the industry to develop a data culture mindset. The 2022 PDA Data Integrity Workshop in September, which he is involved with, will include discussions on data culture. 

“We need a data culture. We need to see data as an asset. No longer is data a burden. Data is an asset we can work with.”

Additional Data Integrity Resources

Can a Robust Quality Culture Help Prevent GMP Issues Such as Data Integrity?

FDA Regulators Address Data Integrity and Lab Audit Trails 

Quality Agreements: Part I, Why They are Critical

Quality Agreements: Part II, How to Write Good Ones

Ensure Adequate Investigations at Your CMO With a QRM Mindset

Warning Letters FY2020 and FY2021

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