In 2008, the International Council for Harmonisation (ICH) issued a guideline on the Pharmaceutical Quality System Q10, referred to as “ICH Q10.” The objectives of ICH Q10 include:
a. Product realization
b. Establishing and maintaining a state of control
c. Facilitating continual improvement
ICH Q10 positioned knowledge management as an enabler for the Pharmaceutical Quality System (PQS), indicating that effective knowledge management is necessary to achieve an effective PQS and, consequently, to meet the goals of ICH Q10. This regulatory guideline marked the first time the concept of knowledge management was introduced within the context of PQS.
Formal research on knowledge management in the biopharmaceutical sector was conducted by Keane in 2014 [1]. At that time, there was little guidance available to describe how knowledge management might actually enable a more effective pharmaceutical quality system. Keane’s research led to the development of a model called the Pharma Knowledge Management Blueprint, which includes four key elements, one of which is the Pharmaceutical Product Knowledge Lifecycle (PPKL) model. Specifically, this model asserts that the pharmaceutical product lifecycle diagram presented in ICH Q10 [2] does not account for multiple instances of technology transfer that typically occur throughout a product’s lifecycle, nor does it address the generation and acquisition of tacit knowledge produced during manufacturing or continuous improvement activities during technology transfer. Keane’s model replaces the ICH Q10 technology transfer lifecycle stage with a more advanced lifecycle stage termed “new product introduction,” emphasizing the need for technology and knowledge transfer throughout the entire product lifecycle.
The PPKL model expands the concept of technology and knowledge transfer (as highlighted in the orange bar of the figure above) and asserts that this model ensures future research opportunities in the areas of new product introduction and technology transfer. It is currently included in the draft of ICH Q12 [3], under the technical and regulatory considerations for pharmaceutical product lifecycle management. The goal of ICH Q12 is to reduce post-approval change submissions by leveraging enhanced product and process knowledge, as accumulated knowledge during development and change implementation helps manage product quality risks.
A review of recent literature underscores the importance of successful technology and knowledge transfer for achieving effective technology transfer outcomes. PDA Technical Report No. 65 on Technology Transfer [4] states that “technology transfer can impact drugs and patients,” clearly emphasizing the significance of effective technology transfer to ensure product outcomes and protect patients. Given that the most critical aspect of technology transfer is knowledge transfer, the following points regarding the effectiveness of knowledge transfer during technology transfer should be considered:
“…assays have been transferred, but the sending party has not provided complete information, or some of the information was outdated…” [5]
“…poor process understanding, coupled with incomplete documentation of all required process parameters…” [6]
“The third mistake is failing to arrange expert-to-expert interaction during the technology transfer process. Experts from similar departments in the technology-sending and technology-receiving companies must closely interact and collaborate during the transfer process; otherwise, the likelihood of technology transfer failure increases.” [7]
“…incomplete knowledge transfer… remains a persistent issue…” [8]
“…no primary document exists to track all information, and data is sent in fragments to different departments…” [9]
“…providing incomplete information about the nature of the biopharmaceutical molecule or protein, such as its properties, activities, and stability under various conditions. Often, companies possess this information but fail to transfer it…” [10]
The above issues lead to deficiencies in knowledge transfer regarding processes, resulting in the following consequences:
- Reduced process capability, e.g., Cpk
- Decreased reliability
- Reduced production yield
- Increased frequency of unusual events (e.g., defects, out-of-specification, out-of-trend occurrences, etc.)
- Challenges in reviewing changes (raw materials, process controls, etc.)
- Inefficient validation
- Heightened manufacturing risks (contamination, cross-contamination, endotoxins, etc.)
The following sources provide valuable insights into technology transfer, though each has strengths and weaknesses, as summarized in the table below:
- WHO Guidelines on Transfer of Technology in Pharmaceutical Manufacturing
- ISPE Good Practice: Technology Transfer, 2nd Edition
- ISPE Good Practice: Technology Transfer, 3rd Edition
- PDA Technical Report, No. 65, Technology Transfer
- PDA Tech Transfer Interest Group Report Out, PDA 2019 Annual Meeting (presentation)
References:
[1] P. Kane, A Blueprint for Knowledge Management in the Biopharmaceutical Sector, Dublin: Dublin Institute of Technology, 2018.
[2] International Council for Harmonisation, “Pharmaceutical Quality System Q10,” ICH, Geneva, Switzerland, 2008.
[3] International Council for Harmonisation, “Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management,” ICH, Geneva, Switzerland, 2017.
[4] Parenteral Drug Association, Inc., “Technical Report No. 65 – Technology Transfer,” PDA, Bethesda, 2014.
[5] S. Perry, “Tech Transfer: Do It Right the First Time,” 06 January 2010. [Online]. Available: https://www.pharmamanufacturing.com/articles/2010/007/. [Accessed 01 February 2019].
[6] W. Schmidt and I. Uydess, “Keys to Executing a Successful Technology Transfer,” Pharmaceutical Technology, vol. 2011 Supplement, no. 2, pp. 1-5, 2011.
[7] A. Shanley, “Getting Biopharmaceutical Tech Transfer Right the First Time,” in Outsourcing Resources 2017, London, BioPharm International, 2017, pp. 27-31.
[8] World Health Organization, “WHO guidelines on transfer of technology in pharmaceutical manufacturing, WHO Technical Report Series, No. 961,” WHO, Washington, 2011.
[9] ISPE, “Good Practice Guide: Technology Transfer, Second Edition,” ISPE, Tampa, 2014.
[10] ISPE, “Good Practice Guide: Technology Transfer, Third Edition,” ISPE, Tampa, 2018.
[15] ISPE, “Good Practice Guide: Technology Transfer, Third Edition,” ISPE, 2018, Tampa.
