by Dr. Yukio Hiyama

hiyama-yukio_2014I am delighted to see details emerging with expanded presentations on knowledge management, particularly the case studies from industry, in this e-supplement from ISPE. The ICH Quality Implementation Working Group (QIWG) team, of which I was a member, could not provide such practical advice on the topic at the time of our work.

Early ICH Discussion and Japanese Regulation Change

First, let me present my personal reflection on knowledge management related issues at ICH and in regard to the regulatory framework development for 2005 Pharmaceutical Affairs Law (PAL) change of Japan.

In July 2003, the ICH GMP workshop adopted the following vision: “Develop a harmonised pharmaceutical quality system applicable across the lifecycle of the product emphasizing an integrated approach to risk management and science.” The US FDA, who proposed the workshop, suggested knowledge sharing and transfer models, as a basis of efficient post approval change management and defined optimal knowledge content and knowledge sharing as agenda items for discussion in their proposal.1 The MHLW presented the new Pharmaceutical Affairs Law framework to become effective in 20052 and the outcome of the 2002 MHLW study.3 At that time, MHLW expected ICH to take on technology transfer, as the MHLW study in 2002 had identified poor communication between Research & Development (R&D) and manufacturing as one of the significant problems. The study group sorted key information that should be transferred from R&D to manufacture and issued a Technology Transfer Guideline.

The PAL change in 20054 was intended to allow the (Japanese domestic) pharmaceutical industry to contract out manufacturing activities. Very often contract givers are R&D based organizations, while contract recipients are of course manufacturing organizations. This was one of the reasons why the Japanese authorities had significant concerns over the effective communication between R&D and manufacturing.5

Having those concerns in mind, I participated in the ICH discussions in the following years. The first ICH Q10 meeting in November 2005 produced a proposed structure of the Quality System Guideline. The initial structure contained four chapters:

  1. Introduction
  2. Pharmaceutical Quality Management System
  3. Management Responsibilities
  4. Life Cycle Models

The Life Cycle Models Chapter had a subchapter called Technical Transfer/Knowledge Management with a note; “resolve terminology Knowledge Management: intent manage knowledge through lifecycle.” The subchapter had an additional heading of Organizational Learning (i.e., learn from one product to next). This represents the early thinking about KM by the Q10 team.

In October 2006, the team produced draft version 8.0 which went outside the team for the first time. The draft expanded the Life Cycle Models Chapter into two separate chapters for Product Lifecycle and for Quality System Lifecycle. Knowledge Management (KM) and Quality Risk Management (QRM) were then described as principles and tools in the Product Lifecycle Models Chapter. At that time, there was NOT consensus on the difference between the Quality system’s elements (or functions) and tools that should be used in the quality system. After extensive discussion, the team reached a conclusion that QRM and KM are the most important tools that should used in the quality system and declared that they are not PQS functions. In the step 2 document for public consultation issued in May 2007, the two tools are finally identified as Enablers. The four PQS elements (Monitoring System, CAPA, Change Management System and Management Responsibilities) are required directly as tasks in the PQS while QRM, KM and others are tools to ensure the performance of the PQS. This was confirmed by extensive discussion at Q10 meetings between draft 8.0 and final step 4 document.6 Later, in order to reconfirm this, QIWG wrote the Q&A document7 stating that KM is not a system and that there is no regulatory expectation to see a formal knowledge management approach.

Are you interested in reading the full article? Download a complimentary copy of Pharmaceutical Engineering Magazine Knowledge Management Supplement here.


  1. FDA Proposal, ICH Workshop July 16-18, Brussels, Belgium, Circulated on 30 June 2003.
  2. Makiko Isozaki, “MHLW’s View on the Quality Regulations for the 21st Century,” ICH GMP Workshop in Brussels, July 2003.
  3. Yukio Hiyama, “Studies on Quality Assurance supported by Health Sciences Grant (H14-Iyaku-04),” ICH GMP Workshop in Brussels, July 2003.
  4. Before 2005, manufacturing contracts were not allowed under the manufacturing authorization framework. The 2005 law change introduced the Market authorization framework where manufacturing contacts are possible. The frame work before 2005 was seen discrimination against Japanese industry because industry outside of Japan was allowed to contract manufacture under the importing authorization framework that co-existed with the manufacturing authorization.
  5. PMDA conducted the first foreign GMP inspection in fall of 2005. As significant concerns were expressed earlier, discrepancy between manufacturing practices and the content of submission is often cited by PMDA foreign inspection.
  6. ICH Q10 guideline.