Why Pharmaceutical Companies Need an Enterprise Quality Management System WHITE PAPER
Overview
Most pharmaceutical executives view quality management as a cost center for the organization despite its potential to generate revenue. Pharmaceutical manufacturers typically lack control over and visibility into quality processes throughout the organization, which remains a profit challenge in today’s market. While all manufacturers have standard operating procedures (SOPs) in place for quality operations, how do executives know if individuals across the company’s various business units and geographic regions are following procedure? The pharmaceutical industry is displaying a growing trend in outsourcing clinical trials and using contract manufacturers and offshore raw materials suppliers in the development of drug products. For drug companies, it is often difficult to determine the source of quality issues arising when third party contractors are employed and to maintain ownership and responsibility for the quality of the end product. Global pharmaceutical manufacturers are turning to enterprise quality management systems (EQMS) to take control over quality operations and ensure everyone at every stage of the drug development process in every business unit and region—both internal resources and external third parties—are complying with SOPs, ICH Q10 and Food and Drug Association (FDA) compliance regulations to deliver safe and effective drug products to the marketplace. EQMS provides manufacturers with immediate access to comprehensive information on quality operations. As a result, manufacturers can quickly identify and address deviations and complaints, uncover potential issues and implement global continuous quality improvements to cut quality management costs by up to 30 percent. In this paper, we examine the regulatory, operational and economic challenges facing pharmaceutical executives today as they work to deliver safer drug products in an increasingly regulated and competitive business environment; how a piecemeal approach to quality management increases risks and costs for global pharmaceutical manufacturers; and, how an EQMS implemented as part of a company’s overall business strategy delivers operational and cost benefits that transform quality management from a cost center to a revenue driver.
Challenges Facing Global Pharmaceutical Manufacturers While industry and government regulations clearly spell out the steps pharmaceutical manufacturers must take in order to achieve and maintain compliance, companies are conducting business in an increasingly complex environment. Today a global pharmaceutical manufacturer’s operations are rarely conducted within its four walls. Instead, most manufacturers rely on a wide variety of third parties scattered across the globe—and are responsible for ensuring each one is operating in full compliance with standard operating procedures (SOPs).
Quality Process Variability
While all pharmaceutical companies have in place standard operating procedures (SOPs) around quality operations, how many have the capability to ensure all parties in the drug development and manufacturing processes—both internal and external—are following these procedures? Most pharmaceutical manufacturers today are relying on disjointed systems to manage quality operations. Furthermore, quality process can vary widely from one site to another and manufacturers typically have little visibility into the activities of third party contractors.
Lack of global visibility into quality operations
While pharmaceutical executives are committed to ensure the quality of company branded products , most do not have the
www.spartasystems.com
technology in place to gain an enterprise-wide view of quality operations. In many cases, different departments, business units and sites use individual systems and processes for monitoring product quality, identifying and tracking deviations and incidents, applying corrective and preventive actions (CAPAs), handling complaints and managing change. Without a way to see the “big picture,” pharmaceutical executives cannot confirm that operations are being conducted in accordance with SOPs, placing both the company—and themselves—at risk for noncompliance with ICH Q10 and other regulations, and jeopardizing the quality of products entering the marketplace.
Reactive versus proactive quality management
Those global pharmaceutical manufacturers that lack enterprise quality management systems often find that processes for uncovering and addressing quality issues at the site level are reactive versus proactive. Rather than having access to detailed, accurate and timely quality data and reports that enable the prediction of potential problems, manufacturers are forced to put out fires as they happen. This poses the risk for minor problems escalating into major setbacks that go undiscovered by the company.
Implementing change in a silo
Another drawback of not having a global view into quality operations is that change must take place in a silo. A site uncovers a problem and implements a procedure to fix it but
2
it is difficult for the company to determine whether that same issue could happen elsewhere. As a result, pharmaceutical manufacturers become locked in a cycle of identifying an issue at site level, resolving it and then waiting to see where that problem might happen next. Implementing change in this manner is both inefficient and costly.
The dangers of disparate processes
Without a global change control process in place, changes to quality operations are often made at the site level. Over time, as sites implement changes to resolve issues, processes can become so disparate that finished products are no longer identical. One global pharmaceutical manufacturer experienced this issue during the production of a blockbuster drug. The company’s sites in the U.S. were making independent changes, and with no change control process, executives were unable to identify and address the deivations. When the U.S. Food and Drug Administration (FDA) conducted an inspection of the plants, it determined that so many separate changes had been made that there was no way to verify each site was producing the same drug. The agency subsequently pulled the license on the company’s product. Today, that company is a poster child for the implementation of their global quality management system.
Evolving Regulatory Environment
Oversight of today’s global pharmaceutical marketplace is the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). It is comprised of regulatory authorities and pharmaceutical industry representatives from Europe, Japan and the U.S. who convene to discuss the scientific and technical aspects of drug registration.” The organization’s ICH Q10 Pharmaceutical Quality System guideline describes what a pharmaceutical manufacturer’s quality system must entail based on International Organization for Standardization (ISO) quality concepts and applicable good manufacturing practice (GMP) regulations. The guideline also clearly calls out how the pharmaceutical company’s management is ultimately responsible for product quality. In regards to the quality system itself, ICH Q10 states that the system must include capabilities for process performance and product quality monitoring, corrective and preventive action (CAPA), change management and management review. This includes “appropriate processes, resources, and responsibilities to provide assurance of the quality of outsourced activities and purchased materials.” As for senior leadership’s role in quality system implementation and management, ICH Q10 states that it is the responsibility of senior management “to ensure an effective pharmaceutical quality system is in place to achieve the quality objectives, and that roles, responsibilities, and authorities are defined, communicated, and implemented throughout the company.” It goes on to state how senior management should be responsible for the continuing suitability and effectiveness of their company’s quality management system and “assess the conclusions of
www.spartasystems.com
periodic reviews of process performance and product quality and of the pharmaceutical quality system.” Conclusively, pharmaceutical manufacturers are increasingly global and dispersed, conducting operations across multiple business units and sites and relying on third parties to run trials, supply materials and manufacture drug products. But at the end of the day, it is a manufacturer’s senior leadership that owns quality management and will be held accountable for any quality issues that arise—whether they are caused by those employed by the company or an external contractor. Global Impact of ICH Q10 and Food and Drug Association (FDA) Efforts Recently the FDA has established offices in India and Japan, with plans to expand around the globe. The presence of regulatory bodies has placed a deeper emphasis on compliance guidelines for companies in these regions. A particular area of focus is the alignment of quality system with business practices and SOPs with the expectation that regulatory scrutiny will increase to quickly address drug irregularities and inconsistency globally that have been taking place. Both CDER (FDA/Center for Drug Evaluation and Research) for Pharmaceuticals and CDRH (FDA/Center for Devices and Radiological Health) for Medical Devices have been deeply involved in ICH efforts to harmonize regulatory requirements in global markets by actively supporting and participating in the global harmonization taskforce.
Benefits of a Global Integrated Enterprise Quality Management Solution Operational and economic advantages
With regulators requiring pharmaceutical manufacturers to have in place comprehensive quality management systems that enable executives to ensure the quality of products produced, and the cost and risk implications of taking a piecemeal approach to quality management, leading global manufacturers are turning to enterprise quality management systems (EQMS) to gain visibility into and to take operational control.
Global view of quality operations across the enterprise
When an EQMS is integrated with a manufacturer’s key business processes it enables pharmaceutical executives to manage, track and report on their company’s quality management processes across the entire enterprise. The system must include functionality for incident management, corrective and preventative actions (CAPAs), audit management, complaint handling and change control, so that it is directly aligned with the requirements of ICH 10. Having all quality management processes flow through a single
3
system provides pharmaceutical executives a comprehensive view of their quality operations that they can leverage to make accurate, timely and impactful changes during all phases of drug development and manufacture, and across all business units and among third party contractors and suppliers.
Enforce compliance with SOPs
With all quality personnel leveraging the same platform for their activities and reporting, pharmaceutical executives can put into place enforceable processes to ensure compliance with standard operating procedures (SOPs). An EQMS should be configurable so that all individuals involved in product quality—both internal and external—are not only following the right processes but also executing tasks in the correct order. This boosts the effectiveness of quality operations, improves efficiency and reduces the risk for costly and potentially dangerous errors.
Reduce risk and avoid loss through proactive and comprehensive change
Having enterprise wide visibility into quality operations and a single system through which quality activities are processed and recorded provides pharmaceutical executives with the information and insights needed to make proactive changes. Rather than waiting for a quality related failure, executives can identify leading indicators and intervene before a minor issue becomes a critical and costly impediment in the drug development or manufacturing process. The data derived from an EQMS also enables pharmaceutical executives to implement comprehensive change across their operations rather than just at the site level. When a manufacturer identifies a quality issue locally and determines its root cause it can then use its EQMS to determine which other sites have the same conditions and apply preventative actions to stop the same problem from occurring, or at least intervene in a timely manner to lessen its impact. According to one global pharmaceutical manufacturer, using its EQMS in this way enabled it to significantly improve its bottom line by reducing the number of quality events impacting its operations. For instance, when the company’s executives found out that a piece of manufacturing equipment was shaving fine metal particles into its drug product and determined it was because of the equipment’s settings, they immediately identified all other sites using this equipment and applied CAPAs to address the problem before it adulterated the drug product at these sites. Reflecting on this use of its EQMS system, an executive at the company stated, “The amazing thing about having this single, global quality system is that once you put it in place, money falls out of the bottom of it.” Manage change globally for consistency across operations Having an enterprise wide quality system that is fully integrated with business operations provide pharmaceutical executives with the visibility necessary to ensure all parties in the drug development and manufacturing processes are operating
consistently for efficiency, effectiveness and safety. When a change is necessary on the site level, executives can evaluate its impact and determine whether the same change must be implemented at other sites to maintain consistent product quality and ensure organization-wide compliance with SOPs. The employment of systematic changes generates greater efficiency and lower costs compared with applying a piecemeal approach.
Quality management self-assessment
For global pharmaceutical manufacturers, quality operations can be transformed from a cost center to a revenue generator through the use of an EQMS. The enterprise-wide visibility and control provided through such a system enables executives to make accurate, timely and impactful decisions to quickly uncover and address issues, thereby improving operational efficiency, reducing risk, driving down costs and getting products to market sooner. To determine what benefits your organization can derive from implementing an EQMS, use the following questions to conduct an assessment of your current quality management processes: 1. D o you manage quality processes in the same manner across all phases of your drug development and manufacturing process? Variations in quality management processes not only place you at risk for non-compliance with industry and government regulations, but can also add time, labor and cost to your operations. Pharmaceutical manufacturers have reported that deviations in quality processes can increase costs up to 30 percent. 2. D o you manage quality processes in the same manner across all of your business units, and across all countries and geographic regions? Pharmaceutical manufacturers are required to operate according to their established standard operating procedures (SOPs). Can you use your current quality management system to ensure all personnel across your global enterprise are following procedures and performing tasks in compliance with your SOPs? If not, you are placing yourself at risk for potential regulatory action and jeopardizing the quality of your products. 3. D o you manage quality processes in the same manner both internally and externally? Although many global pharmaceutical manufacturers today outsource various aspects of drug development and manufacturing processes and rely on third party suppliers of raw materials, it is the pharmaceutical company itself and its executives who are ultimately responsible for the quality of the final products. Determine whether your current quality management system is configured to ensure all parties —both internal and external—are following the required procedures to generate products that meet your quality standards.
FDA Regualtions for Quality Management Systems Regulation/Standard
Description
21 CFR Part 4
FDA published 21 CFR Part 4 “Current Good Manufacturing Practices for Combination Products” (Docket No. FDA-2009-N-0435) effective July 2013. This cGMP rule does not create any new cGMP requirements, but rather, it clarifies which cGMP rules are needed to be enforced when producing a combination product as in the following: If the constituent parts of a pharmaceutical or biotechnology product are manufactured and
marked separately and also cross labeled, they remain separate for the purpose of applying cGMP regulations and need to be manufactured under the separate drug device or biologic cGMP’s Companies have two options for single entity and co-packaged combination products
- Demonstrate compliance with the specifics of all cCGMP regulations applicable to each of the constituent parts included in the combination product - Demonstrate compliance with the specifics of either the drug cGMP’s or the device quality system regulation, rather than both, when the combination contains both a drug and device under certain conditions. These conditions include demonstrating compliance with specified FDA provisions from the other of these two sets of CGMP requirements. 21 CFR Part 11
The FDA regulation that defines the criteria under which electronic records and electronic signatures are considered to be trustworthy, reliable and equivalent to paper records. A Quality Management System (QMS) supports this life science industry regulation by ensuring the software is compliant using secure, automated processes including CAPA, complaint management and risk management.
21 CFR Part 58
Good laboratory practice for non-clinical laboratory studies. QMS process software is available to help pharmaceutical companies electronically manage CAPA, audits, complaints, change control and risk management.
21 CFR Part 110
Current good manufacturing practice in manufacturing, packing, or holding human food. An enterprise quality management system ensures compliance, improves quality, and reduces costs by centralizing and integrating quality processes, including management and reporting of deviations, complaint handling, supplier quality, internal and external audits, change control, corrective and preventive actions (CAPA), preventive maintenance and calibration, and others.
21 CFR Part 210
Current good manufacturing practice in manufacturing, processing, packing, or holding of drugs. A quality management systems (QMS) provides compliance, improves quality, and reduces costs by centralizing and integrating quality processes, including management and reporting of deviations, complaint handling, supplier quality, internal and external audits, change control, corrective and preventive actions (CAPA), preventive maintenance and calibration, and others.
21 CFR Part 211
This ruling requires the manager of any regulatory controlled manufacturing company to manufacture all medicinal products so as to ensure that they are fit for their intended use, comply with the requirements of the Marketing Authorization and do not place patients at risk due to inadequate safety, quality or efficacy. A quality management software solution provides automated processes that achieve the highest level of safety and efficiency required by law to meet this FDA standard.
21 CFR Part 1271
Companies are required to create a unified registration and listing system for establishments that manufacture human cells, tissues, and cellular and tissue-based products (HCT/P’s) and to establish donor-eligibility, current good tissue practice, and other procedures to prevent the introduction, transmission, and spread of communicable diseases by HCT/P’s. This requires companies to register and list HCT/P’s with the Food and Drug Administration’s (FDA’s) Center for Biologics Evaluation and Research, whether or not the HCT/P enters into interstate commerce. A quality management software solution addresses the government requirements through automated processes including product registration tracking.
Regulation/Standard
Description
FDASIA (Food and Drug Safety and Innovation Act), Title VII – Drug Supply Chain
In effect as of July 2012, this regulation addresses some of the supplier management challenges, creates new systems and makes other changes to ensure the safety of drugs through domestic and foreign establishment of registrations, inspections and new penalties. A QMS allows companies to automate vital quality processes that enable conformance to this new legal regulation including CAPA, auditing and supplier quality management.
European Union’s Falsified Medicines Directive
In effect as of July 2012, this directive is designed to address counterfeiting in Europe, whereby pharmaceutical manufacturers must audit their suppliers and distributors, who are required to follow good manufacturing practices and good distribution practices. An audit management solution ensures compliance to this directive and improves quality and reduces costs by centralizing and integrating audit processes. Having an audit process that integrates with a quality management system allows for consolidated data management, visibility across the enterprise and single source of truth.
ISO 9001
The most commonly used international standard that provides a framework for a quality management system. ISO 9000 is a name given to a family of standards developed to provide a framework around which a quality management system can effectively be based. A quality management system is a common sense and well documented system that ensures consistency and improvement of working practices. This includes the products and services produced. It is based on standards, which specify a procedure for achieving effective quality management. The ISO 9000 family comprises a number of different standards (ISO 9000, ISO 9001 and ISO 9004). Each covers a different facet of the whole.
ISO/IEC 17025
General requirements for the competence of testing and calibration laboratories are the main ISO standard used by testing and calibration laboratories. It applies directly to those organizations that produce testing and calibration results. The content of ISO/IEC 17025 standard itself comprises five elements that are scope, normative references, terms and definitions, management requirements and technical requirements. The two main sections in ISO/IEC 17025 are management requirements and technical requirements. Management requirements are primarily related to the operation and effectiveness of the quality management system within the laboratory. Technical requirements include factors which determine the correctness and reliability of the tests and calibrations performed in laboratory.
OHSAS 18001
The OHSAS specification gives requirements for an occupational health and safety management system, to enable an organization to control its OH&S risks and improve its performance. It was developed to be compatible with both the ISO9001 and ISO14001 management systems standards. This includes employee and workplace safety, events, observations, etc.
Good Manufacturing Practice (GMP)
GMP refers to the Good Manufacturing Practice Regulations promulgated by the US Food and Drug Administration under the authority of the Federal Food, Drug, and Cosmetic Act. These regulations, which have the force of law, require that manufacturers, processors, and packagers of drugs, medical devices, some food, and blood take proactive steps to ensure that their products are safe, pure, and effective. GMP regulations require a quality approach to manufacturing, enabling companies to minimize or eliminate instances of contamination, mix-ups, and errors.
To learn more about this topic and how Sparta Systems can help, visit www.spartasystems.com Sparta Systems, an industry pioneer and leading provider of enterprise quality management software (EQMS) solutions, enables businesses to safely and efficiently deliver their products to market. Its TrackWiseÂŽ EQMS, a trusted standard among highly regulated industries, is used by quality, manufacturing and regulatory affairs professionals to manage compliance, reduce risk and improve safety across the global enterprise. Headquartered in New Jersey and with locations across Europe and Asia, Sparta Systems maintains an extensive install base in the pharmaceutical and biotechnology, medical device, electronics manufacturing and consumer products markets.
Global Headquarters 2000 Waterview Drive Hamilton, NJ 08691 (609) 807-5100 (888) 261-5948 info@spartasystems.com
European Offices Berlin | London | Tel Aviv | Vienna europe-info@spartasystems.com
Asia Pacific Offices www.spartasystems.com | http://blog.spartasystems.com
Singapore apac-info@spartasystems.com