Building a Solid Foundation for a Pharmaceutical Quality System: Presenting QRM and KM As United Enablers
September 28, 2022
Risk, knowledge, uncertainty, decision-making: They are among the building blocks at the center of the biopharmaceutical industry that guide the daily operations of biopharmaceutical organizations, from the work of scientists during discovery to technicians manufacturing each batch. Indeed, the biopharmaceutical industry is a knowledge-based industry in which organizations satisfy patient needs while gaining competitive advantage by their ability to grow, transfer, and apply knowledge rapidly and effectively.
Many people who read the word knowledge have a certain implicit interpretation of the term such as explicit knowledge in the form of process data, methods, and specifications. But many synonyms used throughout regulatory and industry guidance alike invoke the concept of knowledge. Terms include prior knowledge, scientific knowledge, science, product and/or process knowledge, experience, product development history, expertise, know-how, product and/or process understanding, lessons learned, and so on. Knowledge includes not only explicit knowledge (codified, as in a document), but also tacit knowledge (knowledge in people’s heads, such as know-how, experience, insights, rationale, and lessons learned).
Biopharmaceutical Knowledge and Quality Risk Management
A holistic review of types of knowledge described in regulatory and industry guidance documents reveals a consistent and recurring theme: the expectation that knowledge management (KM) and risk management (RM) (specifically quality risk management (QRM)) will support science and risk-based decisions to ensure product quality (1). Indeed, ICH Q10 positions KM and QRM as dual enablers of an effective pharmaceutical quality system (PQS) (Figure 1).
Figure 1: Knowledge management and quality risk management positioned as enablers of a pharmaceutical quality system (PQS).
Furthermore, similar references emphasizing the need to apply KM and QRM in decision-making can be found throughout quality guidelines from the International Council for Harmonisation (ICH) as well as in guidance by the World Health Organization (WHO), EudraLex, the Pharmaceutical Inspection Co-operation Scheme (PIC/S), and the International Organization for Standardization (ISO) (2). Other industries, such as aerospace, information technology and finance also have published literature recognizing the relationship between knowledge and risk — and KM and QRM.
However, although the biopharmaceutical industry’s journey in QRM maturity presents some opportunity for improvement, it is no secret that its adoption of KM remains in its infancy (3). The often-cited reason for this is that QRM benefits from its own regulatory guidance from ICH, WHO, and other organizations, but no such guidance exists for KM. Digging a little deeper reveals additional, perhaps more fundamental reasons, including that RM as a recognized practice has had a 40-year head start over KM, that there is a well-established body of literature and standards on RM, and that, comparatively speaking, RM is more discrete, less complex, and better understood than KM (4).
Recent studies suggest that recognition of the need to improve KM adoption, capability, and competency in the industry is perhaps in a period of renaissance. This is evident from many sources, including efforts by a number of industry groups (e.g., BioPhorum, ISPE, and PDA) on progressing KM guidance. The first ISO standard on KM was released in 2018 (5). The important positioning of KM in regulatory guidance also is gaining new momentum, with explicit references to KM in ICH Q12, Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management (6), the draft ICH Q14, Analytical Procedure Development (7), and perhaps most prominently, in the draft ICH Q9(R1) (8). Indeed, the draft ICH Q9(R1) guideline contains 23 references to the word knowledge and another three references to knowledge management. Compare that with the initial version of ICH Q9 released in 2005, in which there are only 11 mentions of knowledge and none of knowledge management. This increased frequency of reference to those terms in the draft ICH Q9(R1) guideline suggests a greater understanding and awareness of their importance by key stakeholders.
Given that KM and QRM are positioned as dual enablers of an effective PQS, each is important and contributes uniquely to the PQS goals of establishing a state of control, achieving product realization, and serving as the basis for continual improvement. A 2021 survey of both regulatory and industry stakeholders explored the level of integration between the two enablers (9). A majority (96%) of stakeholders believed that both are highly interdependent as theoretical concepts (as defined and positioned in guidance). However, none of the respondents reported that KM and QRM are fully integrated in practice, and only a small minority (4%) of them said they were intentionally integrated (but not optimally) (Figure 2).
Figure 2: Knowledge management and quality risk management interdependence (survey results).
The survey also included questions about anticipated benefits that could ensue from integrating KM and QRM. Results suggested several inspiring and powerful potential outcomes by integrating the two enablers, including
∙ more data-driven risk assessments
∙ better risk-based decisions