Continuous Improvement – An integral part of the Pharmaceutical Quality System (PQS)
‘Continuous Improvement’ or ‘Continual Improvement’ within a quality system can be described as a process of ongoing improvement of products, services or processes through incremental and/or breakthrough improvements. Within the Pharmaceutical Industry, it’s important that companies ask themselves how continuous improvement has been built into the Pharmaceutical Quality System (PQS). The term may appear in policies and procedures, but how is it demonstrated that is integral to the PQS and that it’s achieving the intended outcome. It’s increasingly becoming clear that there will be more focus on this, with some more recent regulatory publications further exploring this concept.
The History of Continuous Improvement in the Pharmaceutical Industry
Continuous improvement as a concept has been around for decades. It was included in ISO 9001 Quality Management Systems, first published in the late 1980s where a key element in the guideline is the term ‘Improvement’. This was seen as a key principle of achieving quality in any type of business, the other key principles being Customer Focus, Leadership, People Engagement, Process Approach, Evidence-based Decision Making and Relationship Management.
Similar concepts were developed in Japan where Quality Management included creating constancy of purpose for improving products and services, as well as improving the system of production and service constantly and forever, to improve quality and productivity. These concepts later became further developed and are also known as LEAN and Six Sigma philosophies. LEAN and Six Sigma concepts have been gaining some traction in the pharmaceutical industry over the last few decades.
PIC/S Guide to Good Manufacturing Practice for Medicinal Products Part I (PIC/S Part I) was first published in the mid-1990s and is revised regularly. Edition 15 which was recently adopted in Australia, includes the terms “continuous improvement” and “continual improvement” as a requirement within the PQS only five times. Not a lot of further guidance is provided on how this can be implemented and integrated into the quality system; however, it sets the expectations.
Introduction of ICHQ10: Pharmaceutical Quality System
In 2008 the publication of ICHQ10: Pharmaceutical Quality System, provided more detailed guidelines for the development of a harmonized QMS for the pharmaceutical industry. It was recognized that the lack of internationally harmonized Quality Management System (QMS) guidelines could lead to delays in the implementation of continual improvement for existing products due to different regional expectations. Quality system terms, principles, applications, and expectations were explained in more detail than what was previously available within the GMP guidelines. It spans the whole product lifecycle and the aim was that once implemented in a pharmaceutical companywould lead to the achievement of product realization, establish, and maintain a state of control, and facilitate innovation and continual improvement.
ICHQ10 is the guideline that started setting the expectations for going beyond minimum GMP compliance and instead aiming towards increased use of science, risk-based approaches, and continuous improvement, in addition to encouraging the integration of ISO quality and QMS concepts within the PQS. There is also an emphasis on top management responsibilities.
Top Management Responsibility and Quality Culture
It’s becoming more recognized that a QMS/PQS, once implemented, will be more successful with top management accountability and passion for its ongoing success. It should no longer just be the responsibility of the Quality department or be considered as “Quality Assurance documentation”. It includes setting quality objectives at all levels of the organization and implementing a quality culture. To achieve quality, everyone must feel ownership and understand their specific role in achieving and continuously improving quality outcomes.
Recent Publications Relating to Continuous Improvement
More recent publications are expanding on the concept of continuous improvement including ICH Q12-Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management, Published in Nov 2019 and PI 054-1: How to Evaluate and Demonstrate the Effectiveness of a Pharmaceutical Quality System in relation to Risk-based Change Management, Published in July 2021.
And as recent as April 2022, FDA published a White Paper: Quality Management Maturity: Essential for Stable U.S. Supply Chains of Quality Pharmaceuticals discussing quality metrics and their importance in measuring the health of the quality systems and taking it to the next level using the concept of Quality Management Maturity (QMM).
This demonstrates how FDA is moving toward a more holistic approach that integrates metrics with other behaviours and attributes of effective quality systems. Metrics remain an important tool to monitor the overall health of a facility and the FDA’s Quality Metrics Initiative (Draft: Submission of Quality Metrics Data – Guidance for Industry, first published in 2016) is stated as an active and vital aspect of Quality Management Maturity (QMM) program development. It’s considered the next step from the implementation of ICHQ10 principles.
The Future of Continuous Improvement within the Pharmaceutical Industry
Gradually, it is becoming clear that compliance with GMP will be required at a minimum, but in a modern cGMP environment, this should then also include the application of science and risk-based approaches which lead to both a state of control and continual improvement.
An effective quality system is and will continue to be the foundation for achieving product realization, a state of control and continual improvement. The industry will likely be expected to be more proactive than reactive when it comes to demonstrating an effective PQS.
Traditionally, improvements in the cGMP environment came out of a reaction to deviation/non-conformance rather than from the need to reduce e.g. process variation. And it’s still typical for inspections to be very compliance-focused, and without much emphasis on the use of science and risk-based approaches for driving a state of control and continual improvement.
So, How Can You Demonstrate Continuous Improvement in Your PQS?
So, how can a pharmaceutical company demonstrate that continuous improvement is an integrated part of the PQS and that it’s applied proactively?
Below are listed some specific areas within the quality system and the business in general, and some considerations:
|Quality Policy||Include something about continuous improvement, showing that it’s advocated and integrated into the company culture|
|Quality Plan||Plans and objectives have buy-in from all areas and include continuous improvement|
|Product Lifecycle Management (1)||The system includes details on how a state of control is maintained and how changes and continuous improvement are managed|
|Asset Management||Include asset lifespan assessment|
|Deviation and CAPA||Incorporate identifying continuous improvement actions as documented corrective and/or preventive actions and include effectiveness check|
|Change Management (2)||Processes include a continuous improvement change category and effectiveness check|
|Risk Management||Include identification of continuous improvement actions, that may not be scored high risk, however, may still contribute to reducing the risk of failure|
|Process/Product Performance checks||Identifies sources of variation affecting process performance and product quality for potential continual improvement activities|
|Self-inspection||Include continuous improvement checks and actions, and “Recommendations’” and “Opportunities”are assessed and prioritised|
|Training||Includes how the company embraces and implements continuous improvement initiatives. GMP training includes an explanation of the concept and how this is applied in the PQS|
|Quality Metrics||The overall health of a facility and systems that drives continuous improvement initiatives. Initiatives are captured and actioned.|
|Product Quality Review||Includes review of continuous improvement in the period assessed and impact|
|Management/QMS Review||Supports continuous improvement and includes a review of continuous improvement in the period assessed and impact. Further continuous improvement is identified and actioned.|
|New ideas||Ideas for continuous improvement of products and processes are encouraged, captured, assessed, prioritized and rewarded|
(1) Refer also: ICHQ12-Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management, Published in Nov 2019
(2) Refer also: PI 054-1: How to Evaluate and Demonstrate the Effectiveness of a Pharmaceutical Quality System in relation to Risk-based Change Management, Published in July 2021
Obstacles When Implementing Continuous Improvement Initiatives
One obstacle to implementing continuous improvement initiatives may be that a process or product change cannot be implemented until a regulatory PAC (Post Approval Change) has been submitted to the regulator in each market and in some cases must be approved by the regulator, before being implemented.
Another reason could be a culture of ‘why change it if it’s working’, as a change, in general, may be perceived as resource intense, non-value added and expensive. This strategy may work in the short term, but planning could prove better than having to deal with multiple breakdowns and failures, e.g. an ageing facility with ageing equipment. Risk Assessment is a useful tool, and equipment should include, for example, estimations of equipment ‘lifespan’. After this lifespan is reached, the asset is decommissioned (or at least reviewed, and with justification, the lifespan is extended), recognizing that all equipment will deteriorate and eventually fail.
In conclusion, more recent publications, and in particular the white paper from FDA are providing more details on future regulatory expectations in relation to pharmaceutical companies demonstrating the integration of continuous improvement within the Pharmaceutical Quality System and going beyond just “compliance with GMP”.
Compliance alone will likely no longer be considered acceptable, and the industry will over time be pushed to demonstrate a mature, effective PQS. It will be interesting to see how FDA and other regulatory agencies go with this in the years to come.
And finally remember: Continuous Improvement is as Journey, not a Destination.
PharmOut has been involved with helping countries in the past with PIC/S compliance, including non-member countries, read more and read here about one of our colleagues helping the Saudi Arabian health authorities.
If you would like more information or advice on compliance with PIC/S GMPs, feel free to contact us at one of our offices around the world and we will try to help.
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