ICH Q10: IMPLEMENTATION THROUGH TOTAL PROCESS QUALITY IMPROVEMENT - 1

Part I: Transformational oversight using Quality Cycles for ICH** Q10 implementation

The concept for Total Process Quality Improvement (TPQI) has been developed for implementation of ICH Q10 as a Pharmaceutical Quality System.

Where current Good Manufacture Practice (cGMP) regulations describe the do's and don'ts to achieve products of consistent quality, safety and efficacy, the internal processes remain dynamic and as such potentially affect the controlled status. This may lead to undesired and out of compliance events. When unplanned events occur, a properly functioning Quality Management System will be able to identify immediate and necessary action(s) for correction, corrective and preventive actions to recover and improve the controlled status preventing reoccurrence of the unplanned event.

Relevant processes are identified at distinct hierarchical levels:

• The Operational level (for product realization).
• The Tactical level (for design, establishment and the improvement thereof)
• All initiated at the Strategic level (based on organizational goals and objectives).

Consistency is achieved by interaction of processes at the hierarchical levels leading to the construction of a Transformative Deming Cycle (Plan-Do-Check-Act) as a starting point for organization wide process identification.

Having conducted audits worldwide, it was found that regardless of local cultures and organizational complexity, there is a gap in understanding between the Good (Pharmaceutical) Practice (GxP) regulated environment and the expectations and commitments at executive level of pharmaceutical organisations. Connecting both worlds is the main challenge.

Effective Quality Systems have to fit into the designed structure identifying interactions and cross-functionality for continual improvement whilst following the strategy of the organisation. In other words, how to connect and align operational compliance related activities within the Product Life Cycle with strategic objectives, whilst taking into consideration challenges and opportunities of the executive management.

From a business perspective quality must pay-off. As such, business principles shall be embedded and reflected throughout the organizational levels. This requires transparency, clear communication and attention towards interaction of transitional processes (Rother, 2010¹).

The ICH is following the process approach in the ICH Q10, the Pharmaceutical Quality System.

Within the process approach of the ISO 9001:2008, the evolvement of processes is limited to improvement by correction and prevention. Attention towards interaction and the transition of processes is essential to achieve strategic objectives and the realization of products wherein GxP compliance shall be a given and never a goal for 100% 'audit readiness'. Balancing the business strategy with regulatory expectations is truly a quality challenge.

The process approach for ICH Q10 and ISO 9001:2008 and the use of risk management as a strong enabler, is a good opportunity to harmonize regulatory Quality Systems approaches for the Product Life Cycle of Medicinal Products and/or Medical Devices and the combination thereof.

Recommendation

Munich, Germany4 June 2024

Qualified Person IMP Pre-Course Session

ICH Q10 Objectives in Eudralex Volume 4

On January 31st, 2013 the adapted Eudralex Volume 4² (EU GMP regulations) came into operation. Amendments to Chapter 1 have been made in order to align with the concepts described in the ICH Q10. The three main objectives to achieve by the implementation of the ICH Q10 model are described in Chapter 1.5:

• Achieve Product Realization
  To establish, implement and maintain a system to deliver products with the quality attributes and including compliance with approved regulatory filings to meet the needs of internal and external customers (patients, health care professionals, regulatory authorities).
• Establish and Maintain a State of Control
  To develop and use effective monitoring and control systems for process performance and product quality, thereby providing assurance of continued suitability and capability of processes. Quality Risk Management can be useful in identifying the monitoring and control systems.
• Facilitate Continual Improvement
  To identify and implement product quality improvements, process improvements, variability reduction, innovations and pharmaceutical quality system enhancements, thereby increasing the ability to fulfill quality needs consistently. Quality Risk Management can be useful for identifying and prioritizing areas for continual improvement.

The Transformative Deming Cycles

The ICH Q10 Pharmaceutical Quality System is established to describe a model for managing quality throughout the different stages of the product lifecycle being based on International Standards Organisation (ISO) quality concepts (ICH Q10, Jan 2011, Section 1.1³). The process methodology within the ISO follows the Deming Cycle and is reflected as "Plan-Do-Check-Act (PDCA)" and is applicable to all processes (NEN EN ISO 9001:2008⁴). Moen and Norman (2009⁵) described the further evolution of the Deming Cycle from PCDA to Plan-> Do->Study->Act in 1993 and broadened this in 2009 to include elements for improvement.

The trigger for creating vision and to follow a logical approach in building an organisation-wide Quality System following the ICH Q10 is found in Hoshin Kanri - The Strategic Approach to Continuous Improvement (Hutchins, 2008⁶). Hoshin Kanri is the precursor for process management elements and quality cycles creating the culture and fundaments for Total Quality Management (TQM). From Hoshin Kanri 'Policy Deployment and Control' it became clear that transformative elements in the Deming Cycle require further differentiation of actions for continual improvement.

Crucial to process improvement is the correct identification, implementation, understanding and control of required action. Differences in expectations following the objectives of an organization versus the operational realization can be complex and include more than following a 'straight forward' Plan-Do-Study-Act quality cycle.

In the author's opinion, the real dilemma is: How to translate managerial routines into understandable practices that include compliance principles for the operational arena? To create this, understanding of vision, expression and expectations is crucial for bottom-up commitment.

The missing link for this was found through an ancient anonymous quote, widely attributed to Sun Tsu (The Art of War, 3rd Century BC):

" Strategy without Tactics is the slowest route to victory. Tactics without Strategy is the noise before defeat."

To create an adaptive organisation with commitment at all levels wherein empowering people in their roles is respected requires identification of the strategy, the tactics and then translated into the operational execution thereof. The reengineering of the Deming Cycle requires differentiation at the hierarchical stages. An organisation-wide effective and functional quality concept should consider the cascading of objectives and devolving responsibilities starting from strategy (aim of the organisation), into tactics (establishment of an organisation including redesign and restructure) and structuring operations (product realization).

The operational quality cycle follows the initial Deming concept Plan->Do>Study(Check) >Act (figure 1). The tactical quality cycle organizes, implements and evaluates actions to correct, sustain, prevent and cohere the establishment (figure 2).The strategic quality cycle starts with Awareness->Plan->Act->Interact (figure 3).

Figure1: Operational Quality Cycle

Figure 2: Tactical Quality Cycle

Figure 3: Strategic Quality Cycle

The communicative hand-overs (transformations) connect the distinct quality cycles of each abstraction stage. Interaction is regarded to be of importance to become logically consistent (cohere), resulting in the organisation-wide Transformative Deming Cycles (figure 4).

Figure 4: Transformative Deming Cycles

The Transformative Deming Cycles connect the distinct abstraction stages of an organisation wherein the establishment of resources (Tactical level) connects the different worlds of managerial routines and the operational execution thereof. The establishment is what both executive management and operational management need for realizing goals and objectives. Due to mutual recognition of the target condition an adaptive organisation is created based on a platform of understanding and improved organisation- wide quality awareness (Rother, 2010).

Total Process Quality Improvement and Performance Measurement

In order to analyse, monitor and improve products, processes and the existing Quality System (as required for the Management Review, ICH Q10 par. 2.6), processes at the distinct organizational stages have to be identified and ordered. The ordering is performed in two directions:

• Chronological following the Product Life Cycle.
• Hierarchical to include Strategy, Tactics, and Operations.

Following the process oriented ISO 9001 (2008) is a logical choice from the perspective of the product life cycle realization process from customer demands to customer acceptance (figure 5).

Figure 5: The ISO 9001:2008 process model aligned with the hierarchical structure

The application of distinct organizational stages embed the functional management aspects according to ISO 9001:2008 and ICH Q10 and this creates better insight into the 'Who, What, Where, When and How', being the essential quality drivers for process control and process improvement.

Equally to the TQM principles as described in Hoshin Kanri (Hutchins, 2008), TPQI enables Operating Excellence by creating an organisation that values and respects people and their creative capabilities. Nowadays, lean activities and cost reduction with personal targets increase the pressure on the individual. On occasion this leads to individuals hiding up or denying any shortcomings and/or failures. This lack of transparency may even be enforced by internal legal initiatives (do not create evidence against ourselves). It is vitally important that organisations create a culture where blame is not attributed to individuals on a regular basis.

The Life Science Industry has a direct ethical responsibility towards their clients that have to rely on consistency in quality of products (patients completely depend on safety and efficacy of applied medication and devices).

Without transparency and ability to learn from mistakes there is no real continual improvement possible. As expressed by Imai (Gemba Kaizen, 19977) it is of no use to start an improvement process (Kaizen) without being able to identify and locate the real problem (Gemba). Appointing and identifying and categorising problems into the relevant processes creates opportunities for improvement and additionally removes the problem from personal involvement, reducing pressure and offering room for creativity to solve the problem. To be able to identify the root cause of problems, it is essential to identify, order and link organizational processes obtaining a coherent network of processes.

To identify processes required at each organizational stage, it is important to understand the relevance of processes at each stage based on fundamental questions.

Recommendation

Hamburg, Germany5-7 November 2024

GMP meets Development

• Processes at the strategic stage cover the 'Reason of Existence' questioning:
• What to realize and who is accountable?
• Processes at the tactical stage cover, maintain and improve the establishment of the organisation questioning: 'Who and what is needed to achieve effective and efficient results?' and 'How to improve our activities?'.
• Processes at the operational stage cover the Product Life Cycle questioning: How to develop and establish safe and effective products of consistent quality?

All processes are organized and covered in the Quality Management System questioning: How to structure and control the performance of our activities?

The total concept for organisation-wide quality is completed by implementation of top-down oriented governance systems and bottom-up escalation systems (figure 6).

Figure 6: Framework for processes at distinct stages based on the ISO 9001

Discussion and progress

A well-functioning quality management system as intended by ICH Q10 requires process understanding and process thinking. Its use should facilitate innovation, continual improvement and strengthen the link between pharmaceutical development and manufacturing activities (EMA, guiding letter to ICH Q10, 31 January 2011). The critical elements to achieve this are communication, cascading of objectives and evolving responsibilities in the complex organisation- wide process network. Within the complexity of an organisation it is of importance to create understanding and commitment at all levels. To achieve this, the Transformative Deming Cycles have been developed to clarify and identify distinct activities respecting the organizational hierarchy. Based on this set up a framework has been drafted following the process structure of ISO 9001:2008 and ICH Q10.

In Part ll of this paper, we will focus on dynamic process understanding and organisation-wide process mapping at the distinct organizational stages. Upon creation of a complete process network, special consideration is given towards the control systems needed for compliance control of applicable regulations as well as the central position of the Management Review.

Besides the process network, the main deliverable of this paper will be a system for performance review and continual improvement with the proper use and understanding of Key Performance Indicators (KPs). It will be shown how TPQI is useful and workable reference for the implementation and structuring of ICH Q10 in existing Quality Systems provided that it is presented in the correct context.

Author:
Henny MP Koch
... is consultant in the Life Science Industry. His company, Qimp Management Systems ltd. focusses on sustainable improvements and business solutions with reference towards well-being and patient safety. For questions he can be reached at hmpkoch@qimp.nl.

Source:
1 Rother M. (2010) Toyota Kata. Rother & ompany, LLC 
2 EudraLex Volume 4 (2012) EU Guidelines for Good Manufacturing practice for Medicinal Products for Human and Veterinary Use, Europäische Kommission, Brüssel
3 Pharmaceutical Quality System (ICH Q10), (31. Januar 2011) European Medicines Agency
4 NEN-EN-ISO 9001 Quality Management Systems - Requirements. (2008) International Standard Organization
5 Moen R., Clifford N. (abgerufen August 2010) Evolution of the PDCA Cycle. http://www.pkpinc.com/files/NA01MoenNormanFullpaper.pdf
6 Hutchins D. (2008) Hoshin Kanri, The Strategic Approach to Continuous Improvement. Aldershot, Hampshire England: Gower Publishing Ltd
7 Imai M., Gemba Kaizen' The Kaizen Institute Ltd. Deventer Kluwer 1997