A fully-integrated quality system uses worldwide regulations and standards as a baseline for quality assurance. Since these may change over time, it is important to scout continually for any variations and implement them across the organization as efficiently as possible. This process ensures compliance and can be streamlined by proceduralizing centers of excellence and forming quality teams that span multiple sites to support key components of the quality system.
A transparent regulatory history informs reliability
A chronological overview of the regulatory history of a CDMO provides an excellent indication of reliability and commitment to quality. Product-specific and good manufacturing practice (GMP) certificates or records are maintained at each site, however elevation to a global level prevents site-specific change by ensuring any corrections are company-wide.
A fully integrated quality system drives continuous improvement
An effective quality system is built of multiple components, each of which is clearly defined to avoid ambiguity. These include management responsibilities, risk management, documentation, change management, corrective and preventive action (CAPA), and process performance and product quality. Since a CDMO will manufacture and package many different products for patient use, at a range of different scales and using a variety of external suppliers, the quality system should be designed to account for and control this diversity. A global IT infrastructure is key to support this.
- Management responsibilities
A structured management system is pivotal to maintaining product quality and safety. Management is accountable to ensure that products are fit for their intended use and comply with appropriate regulatory requirements, meaning that management responsibilities must be clearly-defined. These include establishing, implementing and communicating the organization’s quality policy; developing policies, procedures, and plans that define those elements necessary to meet the quality policy along with regulatory and customer requirements; and ensuring that quality policies, procedures, and instructions are understood, implemented, maintained, and accessible to the appropriate personnel.
Management is also responsible for resource management; recruitment of and organization of training for appropriate personnel; establishment and maintenance of controls related to suppliers and external services providers; quality planning; and regulatory reporting. A well-designed CDMO will be able to provide a clear overview of the organization’s management structure, detailing how this structure fits within the quality system. Through a comprehensive understanding of cross-site responsibilities, management should ensure that both they and their reports are fully aware of the importance of adhering to and sustaining a current knowledge of the organization’s quality policy.
According to ICH guidelines, risk is defined as the combination of the probability of occurrence of harm and the severity of that harm1. To manage risk, drug development and manufacturing is reliant on effective quality risk management (QRM) - a systematic process for the assessment, control, communication and review of risks to the patient and to the quality of the drug product across the product lifecycle.
Following initiation of the QRM process, consideration of each element should be commensurate with the level of risk. This informs improved decision-making should a quality issue become apparent.
Robust QRM can provide regulatory bodies with greater confidence in a CDMO’s capacity to deal with risk, a potential benefit being that the extent and level of direct regulatory oversight may be tailored accordingly.
Clear documentation is crucial to a robust quality system and should meet established quality standards to effectively manage knowledge. World Health Organization (WHO) good documentation and quality management principles state that documentation should provide correct, complete, current and consistent information to meet customer and regulatory requirements2. Documentation should also be concise, legible, accurate and fully traceable.
Quality documentation may include policy documents to describe requirements that must be met; process documents that detail activities through which policy requirements are fulfilled; procedure documents explaining specific actions necessary to execute a task in a way that produces consistent results; and guidelines to provide additional information, instruction, or tools to support various activities in a manner consistent with higher-level documentation. Additional documents such as forms to record information, templates to aid document creation, and documentation to summarize quality meetings are also highly informative.
It is important that documentation is reviewed and approved by appropriate individuals, and that any updates are issued with a new revision number to prevent obsolete documents from use. All documentation should be suitable to meet local requirements. The level of documentation required is generally proportional to the stage of the product lifecycle.
Change is an inherent part of the quality system, intended to identify and implement appropriate quality innovations and improvements throughout the product life cycle. To control change, any modification with the potential to impact quality, safety and efficacy should undergo a process of proposal, evaluation, implementation and review. This includes any change to the product; the equipment, instrumentation and process employed to manufacture it; and the facility at which it is produced. Change management is also applicable to documentation, computer systems, training and regulatory filings.
The underlying principle of change management is to plan, evaluate, approve and implement change efficiently. A structured change management process should be clearly documented and comprise identification and justification of the change; notification of areas impacted by the change; assessment to evaluate the impact of the change; implementation of the change, including appropriate application of change control systems and updates to regulatory documents if required; and evaluation of the change to confirm the change objectives were achieved and that there were no unintended consequences of the change on product quality.
- Corrective and preventive action (CAPA)
The FDA states that the purpose of a CAPA system is to collect and analyze information; identify and investigate product and quality problems; and drive appropriate and effective corrective and/or preventive action to prevent their recurrence3. The CAPA process supports continuous process improvements in quality system metrics, helping to ensure effectiveness and compliance.
A robust and transparent CAPA strategy is fundamental to maintaining control. It is used to monitor, measure, analyze and improve the quality system through a process of identification, evaluation,
investigation, resolution, implementation and assessment of effectivity. Sources of input to the CAPA system include processes and operations, concessions, quality audits, quality and service records, product complaints/returns, regulatory inspections, vendor qualifications, management review data, and other sources of quality data.
Any activities conducted in support of the CAPA process should be fully documented. Electronic systems provide an easily-accessible, global alternative to paper-based documentation and can streamline CAPA progression via automated routing, notification, approval, and escalation. Additional advantages of an electronic CAPA system include superior reporting and analytics, user-friendly documentation, and streamlined integration with other electronic systems.
- Process performance and product quality
An effective process performance and product quality monitoring system is required throughout the entirety of the product lifecycle to ensure safety, efficacy, and consistent manufacturability for commercialization. This should include process and product monitoring throughout product development to establish a control strategy for manufacturing; monitoring during technology transfer and scale-up activities to further develop the control strategy; application of a well-designed system within commercial manufacturing to ensure performance within a state of control and to identify improvement areas; and post-manufacture monitoring such as stability evaluation to guarantee continued regulatory compliance.
Supply chain and distribution controls also fall within the scope of process performance and product quality evaluation. These include rigorous testing of materials or consumables provided by third party organizations, and auditing of partners to safeguard product quality and safety. Automated systems to monitor process performance and product quality promise the potential for real-time control and more frequent testing.
A robust and flexible quality system supports clinical success
Nowhere is quality more important than in assuring patient safety. A well-designed quality system will consider every aspect of the drug development and manufacturing process to deliver a safe and efficacious product on time and within budget. With the flexibility to meet exacting customer needs and adapt readily to changes in global regulatory requirements, an effective quality system can expedite time-to-clinic by streamlining processes and procedures worldwide.
Customers choosing to partner with a trusted CDMO for drug development and manufacture can benefit from an established quality policy addressing management responsibilities, risk management, documentation, change management, CAPA, and process performance and product quality. Leveraging the expertise of a CDMO to assure product safety is a proven approach to product realization.
With our Lake County sites used regularly as a training facility for the FDA, AbbVie is recognized as a leader in quality assurance. Our global quality system provides the necessary flexibility for customization to meet the specific requirements of your product, both during product development and further downstream. Contact us to discuss your specific requirements and learn how we can expedite your drug product to market.