MetricStream's Quality Solutions - Power Your Enterprise

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Quality issues facing the pharmaceutical industry
Pharmaceutical companies need to comply with multiple regulations imposed by various organizations. These include the US Food and Drug Administration (FDA), the European Agency for the Evaluation of Medicinal Products (EMEA), the Environmental Protection Agency (EPA), and the Occupational Safety and Health Administration (OSHA). In addition to adhering to the regulations of these authorities, pharmaceutical companies must follow established practices such as Current Good Manufacturing Practices (cGMP), Good Laboratory Practices (GLP), and Good Clinical Practices (GCP). Many of the guidelines and regulations are complex and present a number of practical difficulties in adhering to them and increase the requirements placed on pharmaceutical manufacturers. Notable examples include FDA guidelines on general principles of validation and 21 CFR part 11 guidelines related to electronic records and electronic signatures. The FDA also closely scrutinizes the production validation and complaint management processes, and recent guidelines have placed equal importance on the documentation and corrective action procedures. In addition, there is a strong emphasis on supplier qualification and how it ties into the inspection process of incoming materials (IQA).

Due to the precise nature of pharmaceutical manufacturing, regulatory requirements require that strict controls be integrated to assure precise batch and lot traceability as well as stringent quality control and testing procedures. Sometimes, production is placed on hold until quality experts (QC) approve subsequent processing steps resulting in significant delays due to the variety of tests required.

Historically, companies have not been proactive enough to develop a systematic process to deal with FDA regulations. It is estimated that 30% to 50% of all 483 citations by FDA are related to Corrective Action & Preventive Action (CAPA). In the absence of a CAPA system, compliance system in most companies represent a combination of manual and paper based processes, quality databases and Laboratory Information Management (LIMS) systems. In the absence of an integrated approach, the gaps in quality management process do not permit systematic approaches to identifying root cause problems and managing corrective actions proactively.

Maintaining GxP (the collective term for good laboratory practice, good clinical practice, and good manufacturing practice) environment while upgrading quality systems and moving from paper based systems to electronic records requires a comprehensive and fail-proof method of tracking all quality-related issues and exceptions in real time throughout the organization.

Issues related to 21 CFR Part 11
The FDA introduced 21 CFR Part 11 to guide pharmaceutical manufacturers' handling of electronic records, signatures, authorization processes and traceability. These requirements must be adhered to if an organization chooses to maintain electronic records, including electronic signatures, as part of its compliance procedures. However, compliance to 21 CFR Part11 requires an integrated approach from the pharmaceuticals manufacturers as a fragmented approach will lead to increased information technology (IT) costs, productivity losses and adverse publicity in case of warnings and sanction letters from FDA.

The FDA is becoming more rigorous in its enforcement of Current Good Manufacturing Processes (cGMP) and not just on the control of variability as measured by final product specifications. Post-inspection citations are increasingly referring to 21 CFR 211.110(a) of the FDA's cGMP for finished pharmaceuticals. The strict enforcement of 21 CFR Part 11 has forced pharmaceutical companies to re-evaluate the technology necessary to maintain regulatory compliance. In spite of increased regulatory scrutiny, it is estimated that less than 40 per cent of pharmaceutical, biotechnology and contract research organizations are close to reaching compliance in the lab or with their automated systems (Part 11 Compliance Report, April 17, 2002). Implementation delays are mainly on account of existing manufacturing processes, availability of suitable software and interface issues with the existing legacy systems. Effective compliance with Part 11 calls for an integrated strategy involving users and goes beyond the IT issue involved in compliance.

How companies are responding to the challenges?
Increased FDA pressures are forcing pharmaceutical companies to take a proactive and integrated approach to their quality management strategies. Companies are now focusing on a comprehensive integrated quality management strategy that factors in all quality management factors across all areas of manufacturing operations. Companies are increasingly using IT enabled enterprise, wide quality management systems and web-based platforms such as a CAPA system to navigate through the regulatory maze as well as to realize better operational efficiencies.

What is required for successful enterprise quality management?
As a result of the inability to comply with FDA regulations, the agency has increased its enforcement actions. The companies that have been at the receiving end include Abbott, Eli Lilly and Schering Plough. Abbott's $100 million fine and consent decree, Wyeth's $30 million penalty, the inspection and re-inspection of Eli Lilly and Company resulted in delayed approvals and reduced earning forecasts. Manufacturing problems at several Schering-Plough Corporation facilities led to a delay of FDA approval and loss of bonuses

In order to establish an enterprise quality management system, companies must be prepared to take the most important first step of changing the mindset about how they do business at present. This change must begin at the top and those at the highest level of the company must view quality as an essential business initiative closely tied to the company's competitive advantage. Having responsibility and accountability for quality is a critical role, which cannot be delegated or outsourced. In this regard, it is important to remember that quality is not a line item, or an individual, or a department. The quest for enterprise quality is a culture that needs to be imbibed by all.

As W. Edwards Deming put it: "It is not enough that top management commits itself for life to quality and productivity. They must know what it is that they are committed to--that is, what they must do. These obligations cannot be delegated. Support is not enough; action is required."

Quality is essential for the long-term viability of any business, especially for the pharmaceutical industry. Given the importance of quality management, the top management plays a key role in promoting and supporting the quality culture. The top management should get involved in establishing quality policies and standards for the corporation, provide direction to the quality initiative and benchmark to determine the best quality practices appropriate for the corporation.

Successfully executed Enterprise Quality Management (EQM) initiatives contain the following elements:

• Identification, understanding and documentation of the current quality management processes of the organization
• Understanding of the gaps between the current processes and required processes for implementing enterprise quality management.
• Development and documentation of strategy to satisfy each of the requirements identified by developing a plan describing the organization, quality mission, responsibilities and policies for each element of the business and describing the purpose and scope of each activity the company performs.
• Formation of a project team and management committee to oversee and monitor the implementation milestones, trouble shooting of the problems during implementation and giving overall direction to the efforts.
• Development/modification of draft procedures which meet the business needs of the organization and its comparison with the regulatory requirements to determine whether requirements are being met or not
• Implementation of identified procedures with predefined milestones in terms of time as well as procedures modification
• Carrying out internal audit to determine whether procedures are being understood and followed
• Review by an external consultant knowledgeable in FDA regulations to ascertain whether system meets the FDA requirements in terms of CGMP, 21CFR Part 11 etc.

Factors that can affect the success of Enterprise Quality Management implementation include:

• Lack of top management support: This is one of the biggest implementation pitfalls. If there is no commitment and support from the top management and only a lip service is paid to quality, then the whole effort will be wasted.
• Lack of understanding about the existing processes: Lack of understanding about how existing processes/procedures currently meet the regulatory requirements and the gaps involved in the processes
• Lack of clear communication: Not communicating the objectives/rationale behind the EQM efforts and how it impacts the business.
• Failure to involve everyone in the process: Not involving all employees /teams that will be affected by the implementation.
• Lack of follow-up /Review: Not monitoring the progress of the implementation schedule and working towards a deadline, thereby increasing the amount of time /costs.
• Lack of validation: Failing to conduct internal audits in an atmosphere of freedom to tell the truth and with an effort to understand why the procedures may not have been implemented
• Premature implementation efforts: Jumping into implementation before being ready for it. Not conducting proper gap analysis/requirements analysis thereby incurring additional time/resources and missing out on key issues

Technological developments
Pharmaceutical manufacturers need solutions that can access raw data from multiple legacy sources and new data sources, analyze the data for trends in variability, identify root causes, provide visualization and present an environment that enables real-world manufacturing professionals to improve manufacturing operations while enhancing compliance.

Traditional solutions offered by standalone solution providers provided limited functionality targeted to specific areas of operations, such as clinical trials and non-conformance situations dealing with cGMP, cGLP practices. However, these solutions lacked robustness and lacked integration with other functions and business processes.

The software solution needs of the industry are complex requiring a number of features and interfaces in an integrated manner. Some of the requirements of the industry include:

• Compliance with FDA regulations such as 21CFR Part 11
• Corrective and Preventive Action (CAPA) functionality enabling real time reporting of problems
• Ability to track supplier metrics
• Integrated document and content management
• Interfaces enabling internal and external audits
• Training modules and tools for the users
• MIS capabilities about quality such as cost of quality etc

The pharmaceutical industry stands to benefit significantly through the use of software solutions that enable regulatory compliance and increase operational efficiency. The adoption of CAPA systems is expected to become widespread because of their enabling role in mitigating significant business risks.

The introduction of new process analytical technologies (PAT), i.e. new probe technologies for in-process measurement of quality, is expected to provide new ways for measuring the manufacturing process in real time, providing additional data that will accumulate in new and legacy systems. The FDA has formed a sub-committee dedicated to understanding the potential of this technology and developing guidelines for its use. PAT holds the promise of getting more information quickly into the hands of decision-makers, empowering them to improve quality compliance and improve global operational efficiency.

The new technologies such as CAPA and PAT are expected to enable:

• Review of process and final product parameters in real time
• Defining specifications aligned and consistent with process capability
• Investigation of atypical batches in a faster and reliable manner
• Improved validation of manufacturing processes
• Monitoring and analysis of production trends in a consistent manner
• Speedier preparation of Annual Product Reviews (APRs)

The new technologies will provide the ability to achieve greater process control and stability resulting in shortened process start-up/scale-up times, reduced trouble-shooting time/adverse trend reversal, faster batch release, improved productivity and quality and improved return on net assets (RONA). They will also help mitigate the risks associated with an enterprise-wide compliance strategy, especially when used in conjunction with a phased approach that prioritizes which elements of the manufacturing operation must be brought into compliance first.

The MetricStream Solution - Power Your Enterprise
The MetricStream QMS is a focused, progressive & pioneering compliance solution for the pharmaceutical industry. Its robust and tightly integrated application modules clearly address the process automation and regulatory requirements of pharmaceutical enterprises. Quality*Stream provides standards-compliant solutions to key industry issues using 100% Java and XML -based server architecture. This powerful, pre-packaged solution models industry-wide best business practices within quality management and comprises the following modules:

• CAPA
• Audit Management
• Document Management
• Equipment Management
• Supplier Quality Management
• Inspection
• Training

MetricStream addresses the industry's key business needs through the following product features and functionality.

• The unique Dashboard system provides real-time snapshots of the quality measures across the extended supply chain including cost of quality, unresolved corrective actions and supplier performance parameters.
• A powerful document control module enables the creation, maintenance and retrieval of critical process and quality compliance documents relating to suppliers and internal quality through a secure web interface. The workflow feature also enables the automation of document approvals and escalation procedures.
• The highly configurable alert notification feature allows monitoring and tracking of adverse events, as well as generates sophisticated containment and corrective actions based on root-cause analyses.

MetricStream provides a seamlessly integrated suite of products that facilitates enterprise-wide deployment in a flexible and efficient manner.

Technical Details

• Fully web-based with an intuitive, easy-to-use user interface.
• J2EE and XML compliant, n-tier architecture
• Runs on Windows NT and Solaris
• Tightly integrates with Oracle Manufacturing, Financials, HR and other third party applications.

Fundamentally, progressive and agile systems have successfully pioneered enterprise wide solutions for organizations. The experience, knowledge and skills that converge on a single platform provide the foundations for speed, reliability, scalability and compliance to help migrate 'best of class' enterprise compliant solutions onto large corporations.

MetricStream’s quality and performance management solutions help Pharmaceutical organizations benefit significantly through the use of software solutions that enable regulatory compliance and increase operations efficiency. Through our enterprise-class quality management solutions (QMS) we can help power organizations by reducing administrative and operating costs, achieve business objectives, competitive advantage and increased market share. For more information on implementing solutions for your enterprise, please contact us at 1-650-620-2955, or by email at info@metricstream.com.