Subjectivity in Quality Risk Management

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BioPharm International, Quality and Regulatory Sourcebook, March 2024 eBook, Volume 2024 eBook, Issue 1
Pages: 7-11

The authors discuss subjectivity in the ICH Q9 (R1) guidance document.

Editor's Note: This article was previously published in Pharmaceutical Technology® 2024 48 (3).

In 2020, the International Council for Harmonisation (ICH) published a concept paper (1) that outlined a limited revision to the published guideline ICH Q9 Quality Risk Management (QRM) (2) to address the fact that “the benefits of QRM [quality risk management], as envisaged by ICH Q9, have not yet been fully realized.”

Arguably, despite the publication of the companion ICH guidelines in the first decade of the 21st century, ICH Q9 (2) and ICH Q10 Pharmaceutical Quality System (PQS) (3), there are still numerous challenges in enhancing manufacturing operations, which lead to quality issues and drug shortages. Even with significant efforts in QRM by both the industry and regulators, there are signs that unmitigated risks persist within the pharmaceutical industry, resulting in quality defects as reported by Kevin O’Donnell, Market Compliance Manager at the Health Products Regulatory Authority (HPRA) in Ireland, who observed that the number of total quality defects reported to the Irish regulator between 2002 and 2021 had increased by more than 10-fold (4). In addition, a survey of chief quality officers of 30 global pharmaceutical companies found that the benefits envisioned by ICH Q10 have generally not been realized, and in some cases the situation was slightly worse or more complex (5).

FDA’s 2019 Drug Shortage Report underscored the ongoing problem of drug shortages in the United States, suggesting manufacturers might prioritize cost reduction over quality investment because quality is not viewed as a competitive marketplace advantage (6). Concurrently, the US Senate Committee on Homeland Security drew attention to the escalating trend of essential medication shortages, impacting a broad spectrum of products from emergency hospital drugs to over-the-counter remedies. By the end of 2022, drug shortages reached a new peak. This crisis was rooted in various factors, such as an overreliance on foreign sources for active ingredient, a lack of domestic manufacturing capacity, and insufficient supply chain visibility into all the companies involved, leading to a misleading appearance of supplier diversity. These shortages have profound cascading effects on patient care (7).


As a tangible step to help address some of these challenges, a targeted revision of ICH Q9 was approved. ICH Q9(R1) was published in January 2023 (8), superseding the original ICH Q9 guidance issued in 2005 (2). This revision narrowly focused on the following four topics deemed critical to advance the competency and effectiveness of the industry in risk management:

  • high levels of subjectivity in risk assessments and QRM outputs
  • product availability risks
  • lack of understanding into what constitutes formality in QRM work
  • lack of clarity on risk-based decision-making.

The ICH Q9(R1) concept paper further suggested risk review and hazard identification as two additional points to be addressed.

Considering the topic of subjectivity, the ICH Q9(R1) Concept Paper (1) noted the challenge associated with subjectivity as follows:

“High levels of subjectivity in risk assessments and in QRM outputs—the reasons for this can include highly subjective risk scoring methods and differences in how risks are assessed and how hazards, risk, and harms are perceived by different stakeholders. This can lead to varying levels of effectiveness in the management of risks. While subjectivity cannot be completely eliminated from risk assessment and QRM activities, it may be controlled using well recognized strategies, including addressing bias and behavioral factors.”

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About the authors

Amin Ziaie, QRM Merck & Co., Inc, PRST; Anne Greene is director PRST; and Marty Lipa, PhD, PRST; all at the Technological University Dublin.

Article details

BioPharm International®
Quality and Regulatory Sourcebook eBook
March 2024
Pages: 7-11


When referring to this article, please cite it as Ziaie, A.; Green, A.; and Lipa, M. Shining a Light on the Long Shadow of Subjectivity in Quality Risk Management. Pharmaceutical Technology 2024 48 (3).