【中文翻译02】ISPE 良好实践指南：制药行业的知识管理

The development and manufacture of biopharmaceutical products is a highly complex scientific endeavor, and individuals and organizations have always managed knowledge in various ways and to varying degrees of effectiveness. Anecdotally, there are arguably familiar challenges associated with managing knowledge such as:

• Poor filing systems
• Multiple competing databases
• Different Information Technology (IT) systems across different departments and across the product lifecycle
• Challenges in finding Subject Matter Experts (SMEs)
• Difficulty in understanding why certain decisions were made
• Repeated issues and mistakes (not learning lessons)
• Difficulty in finding historical product knowledge
• Incomplete knowledge transfer

Further, the wide availability of personal computerized systems and various electronic databases has made findability of knowledge increasingly complex. As the pace of data accumulation and the associated knowledge generation continues to accelerate, the need to manage knowledge systematically has become increasingly apparent, important, and expected.

In the pharmaceutical industry, consistency of product quality (composition and performance) within and between lots is critically important for the patient as the ultimate user, and by extension, for all those engaged in its provision. There is now a global general acceptance that the control of product quality must commence during product development and continue up to, and in certain respects beyond, the time of product discontinuation from the market. The Quality Guideline Series from ICH [1] describe foundational principles for the achievement of process understanding and quality throughout the product lifecycle. This is based on the belief that quality cannot be tested into products but rather should be built in by design and demonstrated by the results and conclusions of the development studies undertaken. With new countries joining ICH, the guidelines are approaching a de facto standard, although there remain differences in levels of adoption and regional interpretations.

Within the ICH Quality Guideline Series, the topic of applying prior knowledge, and more broadly Knowledge Management (KM), emerged starting with ICH Q8 [2] Pharmaceutical Development. This has been reinforced in subsequent guidelines. Recommended for adoption in November 2005, ICH Q8 introduced a number of new key concepts including Quality by Design (QbD), Design Space, Quality Target Product Profile (QTPP), and Critical Quality Attributes (CQAs). These concepts are discussed in greater detail in Section 10.1.1.

It is, however, noteworthy that ICH Q8 [2] provides the first reference to the concept of KM in the field of pharmaceutical quality. In ICH Q8, KM is a tool to be used along with Quality Risk Management (QRM) for a more systematic QbD approach to development throughout the lifecycle of the product.

ICH Q9 [3] (also recommended for adoption in November 2005) describes in detail the principles and practices of QRM. While ICH Q9 makes no explicit reference to KM, it makes multiple references to the knowledge available for making risk-based decisions, for example:

“The evaluation of the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patient.”

Following ICH Q9, ICH Q10 [4] was adopted in 2008 and specifically identified KM as one of the two enablers of a PQS, stating:

“Use of knowledge management [italics in original] and quality risk management will enable a company to implement ICH Q10 effectively and successfully.”

Furthermore, ICH Q10 [4] connects the successful implementation of an effective PQS, enabled by KM and QRM, to the interest of public health and establishes the connection to innovation and continual improvement as follows:

“ICH Q10 demonstrates industry and regulatory authorities’ support of an effective pharmaceutical quality system to enhance the quality and availability of medicines around the world in the interest of public health. Implementation of ICH Q10 throughout the product lifecycle should facilitate innovation and continual improvement and strengthen the link between pharmaceutical development and manufacturing activities.”

The realization of this desired state has been central to ISPE’s efforts to advancing the state of pharmaceutical quality within the industry [5], and this Guide supports those efforts by demonstrating the value of systematically managing organizational knowledge as part of that journey.

The incorporation of KM in pharmaceutical organizations has been slower than in other industries [6, 7]. Beyond the specific arena of pharmaceutical quality, KM is becoming more widely recognized as a stand-alone discipline that focuses on ways organizations create, manage, and use knowledge. This is not surprising in the current era where business activities are becoming increasingly dominated by knowledge workers and the widespread utilization of complex digital systems for storing the ever-growing knowledge generated in different types of enterprises. ISO 30401 Knowledge management systems — Requirements [8] was published in 2018 with the stated objective to:

“...support organizations to develop a management system that effectively promotes and enables value-creation through knowledge.”

Thus, KM can be considered as an important enabler of an effective modern management system and the content of ISO 30401 is worthy of consideration. Appendix 15 provides further comparison between this Guide and ISO 30401, including a map of the contents of each document.

This Guide seeks to embrace and advance KM for the pharmaceutical industry.

The practical principles and methods and tools provided in this Guide are intended to help organizations improve their capabilities in managing knowledge and using that knowledge to support an effective PQS resulting in improved organizational performance, among other benefits. One such practical approach is the Knowledge Management Maturity Assessment Tool (see Appendix 3), which can be used to measure an organization’s KM maturity and identify opportunities for improvement.

The goals of this Guide are to:

• Define and explore the meaning and importance of KM in the context of the pharmaceutical industry
• Discuss the importance of KM to the PQS
• Describe KM principles, key concepts, the general KM process, and foundational KM methods and tools
• Discuss forward looking opportunities for KM
• Share practical pharmaceutical applications and case studies of KM

This Guide is relevant to organizations across the pharmaceutical industry in their pursuit for effective and practical solutions to common KM issues.

It is envisioned that the practices presented in this Guide will result in broad benefits to a variety of stakeholders including patients, organizations involved in the discovery and manufacture of pharmaceutical products, regulatory agencies, and the employees of these organizations as knowledge workers. By further socializing and educating on the topic of KM, the understanding and resulting effectiveness of KM methods and tools can be meaningfully improved. The author team of this Guide in turn believes the pharmaceutical industry will be better positioned to realize the important objectives of ICH Q10 [4], ICH Q8 [2], and other regulatory guidances that prescribe the capture and application of knowledge.

The scope of this Guide is aligned with the ICH Q10 [4] scope:

“...systems supporting the development and manufacture of pharmaceutical drug substances (i.e., APIs) and drug products, including biotechnology and biological products, throughout the product lifecycle.”

The principles described may also be applied to medical devices, over-the-counter products, personal care, and cosmetics. In addition, to be maximally effective these principles should be applied throughout the product lifecycle from research and development, technology transfer, commercialization, up to and including product discontinuation.

This Guide provides a variety of materials to advance the understanding of KM and its application in pursuit of improved KM effectiveness and maturity to enable the aforementioned goals. This Guide features:

• A description of the importance and associated benefits of effective KM
• Definitions and principles behind KM and supporting concepts
• Frameworks to enhance the understanding and application of KM
• A section on Getting Started to foster the first steps for a KM effort
• A maturity model to assess the current-state performance and identify opportunities to improve effectiveness
• A variety of methods and tools, and systematic approaches to improve KM effectiveness
• Advice to relate KM to other industry guidance
• Case studies demonstrating the application of KM

This Guide is organized as follows:

• Chapters 1 and 2 explain the Why behind KM
• Chapters 3 and 4 provide basic information on KM to enhance the understanding of What KM is
• Chapter 5 discusses KM Application across the product lifecycle
• Chapter 6 introduces principles for digitally enabled KM
• The appendices provide resources for the How and supplemental information
  • Appendices 1 – 7 discuss KM methods and tools
  • Appendices 8 – 13 present KM case studies
  • Appendix 14 contains example KM templates
  • Appendix 15 is a map of this Guide to ISO 30401 [8]