Jean Smart, RAP
March 2012

Setting up a GXP or quality environment in a research institution, agency or company where none exists can seem a very daunting task. This is certainly the case where there are limited resources and personnel with quality expertise along with a lack of understanding of what is involved in taking on quality initiatives.

There are new initiatives being discussed in British Columbia and in other Canadian jurisdictions for the establishment of a regulatory compliance quality program with systems that can be used as templates for research institutions and agencies. This approach would provide organizations with pre-developed quality management tools, quality education and assistance with the implementation. The main objectives are to achieve regulatory compliance and move into the realm of quality improvement for research.

This article presents some of the main quality terminology, definitions and provides a brief outline of the main quality systems used and expected for research in Canada.

It Starts at the Top

To start, the organization needs to be committed to quality. The organization should have a Quality Policy to define this commitment. The quality policy statement describes an organization’s general quality orientation and indicates the basic intentions. From this, Quality Objectives are developed as a framework for an overall quality program. A Quality Plan is developed from the objectives. A visual framework is often made to show the outline of the program. Functional quality roles are also defined. It is important the quality personnel report to the top, so that they have the leeway to evaluate all aspects of quality in the research organization from top to bottom.

Quality Management

Quality Management has a specific meaning within many business sectors. Within the research sector it means to ensure that an organization is consistent and can be considered to have four main components established: Quality Planning, Quality Control, Quality Assurance and Quality Improvement.

  • Quality Planning – setting the quality objectives and documenting the resources and operational processes that will be needed to achieve the objectives
  • Quality Assurance – refers to the planned and systematic activities that are established to ensure that quality requirements will be fulfilled in compliance with applicable regulatory requirements and standards. It includes the systematic review, analysis of auditing of processes against standards.
  • Quality Control – the routine technical activities that are done within the Quality Assurance system to verify that the requirements for quality have been met. This includes consistent checks to ensure that processes are documented. Data is checked for integrity, correctness and completeness and errors and omissions are identified and addressed.
  • Quality Improvement – anything that enhances an organization’s ability to meet the quality requirements.

Quality management is focused not only on quality, but also the way to achieve it. Quality management essentially uses quality assurance and quality control of processes to achieve more consistent quality. Quality management encompasses all of the activities that organizations use to direct, control and coordinate quality. These activities include the formulating the policy, setting the objectives and planning and conducting quality control, quality assurance and quality improvement. Quality is implemented through the use of a quality management system or systems. The quality policies, objectives, plan and systems are outlined in a Quality Manual or equivalent document.

Quality Management Systems

A Quality Management System (QMS) is a system or a set of systems put in place to direct and control an organization with regard to quality. In research we use a set of interrelated or interacting systems or processes to direct and control how the quality policies will be implemented and how the quality objectives will be achieved. This is also known as a systems approach to quality management.

The common subsystems used in research are: Document Management System (DMS), Auditing System, Corrective Action and Preventative Action system (CAPA), Investigation System, Deviation System, Vendor qualification and Surveillance System and the Continuous Quality Improvement System (CQI). These are all part of the QMS.
The Document Management System is the system that handles controlled documents. Controlled documents include: policies, standard operating procedures, working practices or work instructions, guidelines, forms and templates (optional). A robust DMS has processes for registration, review, change control, archive, control of external procedures and control of internal procedures and indices being released externally. Controlled documents are classified, numbered and versioned. This system is interrelated with the training system.
The Audit System handles internal audits (examples: departments, studies, processes, documentation) and the hosting of external audits. It is related to the observation and CAPA system directly and indirectly to the deviation system in that an audit can identify deviations from procedures or policies.
The CAPA System covers corrective and preventative actions. Corrective actions are steps that are taken to remove the cause of a non-conformity, deviation or undesirable situation. It is designed to prevent the reoccurrence of the non-conformity or deviation by eliminating the cause. Corrective actions address actual problems and this is a problem solving process within the system. Preventative actions are steps that are taken to remove the causes of potential non-conformities or potential problems. This process within the system is designed to prevent the occurrence of nonconformity by eliminating the cause. This is closely linked to risk analysis processes. An advanced CAPA system includes CAPA analysis and root cause analysis. Corrective actions prevent reoccurrence and preventative actions prevent occurrence. The CAPA system is linked to CQI, deviation/observation and audit systems.
The Investigation System is an independent means to investigate an issue. The issue can be a potential or actual problem. Entry into this quality system comes from Observations, audits, assessments, privacy incident reports or incident reports. It is a means for the quality manager to assess a situation to information needs to be gathered, risk ascertained, determination of status. Solutions are presented if necessary. This system is interrelated and feeds into the CAPA system, CQI system and some other agency systems such as privacy system if it exists.
The Deviation System monitors deviations from policy, procedure or approved working practices. Deviations can be planned or unplanned. Identified deviations are recorded and tracked. Unplanned deviations can be indicators that a policy or procedure is not working. They can also indicate that there is a training problem. Planned deviations identify when a procedure is not going to be followed due to circumstance. All planned deviations are tracked and monitored for quality. An example of a planned deviation is when an organization follows another agencies operating procedure for a specific project or study. The deviation system feeds into the CAPA system when unplanned deviations are logged.
The Vendor Qualification and Surveillance System is set up to qualify and monitor any vendors used to support general internal services, infrastructure or operations. This is commonly done for agencies or organizations or individuals that will be providing services for which there is a major transfer of responsibility. Qualification of vendors may involve review of qualification documentation, remote review, site inspection or full audit. A Qualified Vendors is a vendor that currently meets the institution or agencies standards and/or regulatory requirements to be a vendor. The surveillance element of the system includesongoing review to ensure that the standards are the same or are improved upon from the time of initial qualification. The qualification time period is defined within the qualification Surveillance program. Vendor qualification is a regulatory requirement for clinical trials in Canada.
Continuous Quality Improvement System works within the framework of continual improvement. It is a system with a focus on linear, incremental improvement within an existing process. There are many types or model for CQI. Generally, they are stepped models for carrying out change. Steps in the process are evaluated and repeated with modifications and further evaluation until improvement is achieved. The main focus of CQI is to continuously assess the results. The models and processes within this system usually include planning, implementation on a small scale, evaluation using measurable outcomes and implementation on a wider scale. This system is interrelated with the CAPA system and root cause analysis and associated with risk analysis programs.

Validation

Validation is the quality process that stands alone. In research, the computerized systems that we use are required to be validated. Validation is the process that uses objective evidence to confirm that the requirements which define an intended use or application have been met. A standard methodology is used. The documented evidence provides a high degree of assurance that the computerized system will consistently meet its predetermined specifications and quality attributes. The process of validation is usually carried out in a simulated use or test environment before going into production. However, realistic use conditions can be used in some instances. When all requirements have been met a validated status is achieved and the system can be authorized for release by the quality manager for use.

Institutions and agencies create highly defined procedures for computerized systems validation, along with template plans for validation and migration projects. Incremental Validation exercises are performed if there is a planned change on a previously validated system. Ongoing general review and reassessment are part of the validation process. Quality assurance is done in the planning stages and at each and every step of the validation process.

The Bottom Line

We have been talking about the requirement for quality in research for two decades. The ICH E6 Good Clinical Practice with the requirement for having Quality systems and procedures was adopted in Canada in 1997 and was passed as regulation in 2001. Internationally, GCP has since become the basis for good research practice.

Interestingly, it is still not uncommon to find quality management in place and well established on the clinical side of an agency but absent on their research side. Health Canada’s GCP Compliance program’s most recent Inspectorate’s Report “Summary Report of Inspections of Clinical Trials Conducted from April 2004 to March 2011 suggests that quality systems and procedures are still missing in Canada. It was the number one finding over the seven year period coming at 27% of all findings. Many global regions also recognizing this, have starting developing collaborative and accessible quality programs.

There is no question quality management requires a commitment on the part of the organization. It also requires expertise and resource. It is definitely time to make the move towards a introducing a collaborative effort towards the development of quality management programs so that they are available for all.

References

Government of Canada, Food and Drugs Regulations Division 5 Amendment Schedule 1024, July 2001. c05.012 and c05.013.

Health Canada, GUIDE 0068 Guidance for Records related to Clinical Trials, June 15, 2006.

Health Canada, Summary Report of Inspections of Clinical Trials Conducted from April 2004 to March 2011, March 2012

International Conference on Harmonisation. Guidance for Industry: Good Clinical Practice – Consolidated Guidelines, ICH Topic E6: Technical Requirements for the Registration of pharmaceuticals for Human Use. 1996. Adopted by Health Canada in 1997. Enacted July 2001.
International Organization for Standardization (ISO), Standard 9000:2005: Quality Management Systems – Fundamentals and Vocabulary, ISO, Edition 3, October 16, 2005, pgs 30.
International Organization for Standardization (ISO), 9001:2008 – Quality Management Systems Requirements, ISO, 4th Edition, November 15, 2008, pgs 36. (Replaced ISO 9001:2000).
Pharmaceutical Inspection Convention Pharmaceutical Inspection Cooperation Scheme, PICS Annex 11, Guide to Good Manufacturing Practice for Medicinal Products – Computerized Systems, 5 April 2007.