For decades, the pharmaceutical industry has managed its business by focusing most of its resources on the next blockbuster drug. With changes in regulations, declines in drug approvals and a shift toward developing high value biologics, today’s manufacturers must begin to refocus and address current processes, practices and systems, and take a hard line on improving their overall quality and compliance efforts. This article will explore how one company determined the health of its quality manufacturing systems by assessing its current quality systems, developed Key Performance Indicators and learned best practices to address and resolve all high risk areas. With more than 50 percent of Form 483 observations and warning letters citing Corrective Action/Preventive Action (CAPA) deficiencies, we will provide tips for developing effective CAPAs and define CAPA Effectiveness.
And, with the FDA’s request for more authority to ensure the public’s safety, we will discuss Change Management, including elements of the system and industry challenges. Lastly, we’ll explore Management Review, providing examples of FDA warning letters to highlight current industry issues and reasons why the manager is no longer the manager.
A Quality System is the organizational structures, processes, procedures and resources used to manufacture pharmaceutical products in accordance with applicable regulations. This entails quality planning, quality control, quality assurance and quality improvement for achieving consistent product quality. The objective of a Quality System is to achieve product realization, establish and maintain a state of control and facilitate continual improvement across the different lifecycle stages. The major components of a products lifecycle are pharmaceutical development, technology transfer, commercial manufacturing and product discontinuation.
Key Elements to a Quality System
The elements of a Pharmaceutical Quality System, as described in International Conference on Harmonization (ICH) Q10 Pharmaceutical Quality System Guideline, outline the effective quality systems for the pharmaceutical industry. The systems are designed to be used throughout each stage of the products lifecycle. The Quality System consists of these four key elements: Process Performance and Product Quality Monitoring, Corrective Action and Preventive Action (CAPA), Change Management, and Management Review of Process Performance and Product Quality.
I. Process Performance and Product Quality Monitoring System
A process performance and product quality monitoring system ensures that pharmaceutical companies are operating in a state of control. The system should provide assurance that the processes and controls produce products with safety, efficacy and quality. These systems include risk management, statistical tools, quality control, process excellence tools, supplier/material management, internal/external source review and validation.
An example of a process performance and product quality monitoring system are Key Performance Indicators (KPIs). The following case study illustrates how one company benefitted from outsourcing a quality systems assessment to determine the state of their Quality Systems.
The Benefit of KPIs in a Global Quality System
Overview: A consulting firm was retained by a mid-sized global pharmaceutical company to assess their current quality systems and develop Key Performance Indicators (KPIs) to determine the health of their quality manufacturing systems. A scorecard was developed to monitor the performance of the quality system in terms of achieving the set targets. The client company’s Global Quality Assurance (GQA) organization proactively retained the consulting firm to provide ongoing compliance support for KPI/Metrics evaluation and remediation, as well as overall compliance support in the following areas: Regulatory Intelligence Vendor Management Internal Audits Stability Program.
Scope: The assessment required an understanding of the client company’s existing quality systems, as well as federal and international manufacturing regulations and guidances. The assessment involved several quality systems within the Global Supply Chain. The consulting firm used the DMAIC methodology of Define, Measure, Analyze, Improve and Control to improve the Quality System.
Methodology: During the project, the following key activities for KPI/Metric review were performed:
1. On-site Assessment of the following:
- Corrective Action Preventive Action (CAPA) System
- Deviation/Investigation System
- Change Control System
- Complaint Program
- Training Program
- Internal Audit Program
- Documentation Management System
- Stability Program
- Supplier Control Program
2. A thorough Data System Review of every existing electronic system that is capturing data.
3. Based on Data Review, a Score Card for the Quality System was developed, highlighting statistical targets as well as industry standard targets based on historic performance.
4. A Global Dashboard to provide an overall score indicating compliance risk level for their total quality system.
5. Weekly Global Supply Chain Status Meeting discussions with leadership team to ensure clear communication regarding project progress as well as remediation of issues.
6. Monthly Senior Executive Leadership presentations for the executive board regarding KPI/Metrics progress.
7. Quality System remediation plans for high-risk areas discovered within the quality system.
Deliverables: The consulting firm provided the observations made as a result of the assessment activities during a review with the client company’s key stakeholders in the project. After the review, the firm provided the complete set-up of the dashboards for each quality system and the global dashboard, which included all calculations and targets. The firm also provided an action plan outlining best practices to address and resolve all high risk areas in a timely, compliant fashion which later resulted in the firm implementing the client-approved action plan.