Goals
When you have completed this unit, you should be able to:
a. Perform an audit of a change management system.
b. Use a range of tools and information, including the contents of this unit and the internet to support the audit of a change management system.
c. Understand and apply appropriate GMP standards/regulations to an audit of a change management system.
d. Recognize compliance or non-compliance of a change management system to applicable regulations.
Definitions
Change Control: A formal process by which qualified representatives of appropriate disciplines review (including technical and operational impact assessment), authorize, approve and close proposed or actual changes to facilities, systems, equipment and processes to ensure that they are maintained in a controlled manner.
Explanation of Topic
Introduction
Planned changes may be proposed to a starting material, product component, process equipment, process environment (or site), method of production or testing or any other change that may affect product quality or reproducibility of the process. Written procedures should be in place to describe the actions to be taken if such a change is proposed. Change control procedures should ensure that sufficient supporting data are generated to demonstrate that the revised process will result in a product of the desired quality, consistent with the approved specifications.
All changes that may affect product quality or reproducibility of the process should be formally requested, documented and accepted. The likely impact of the change of facilities, systems and equipment on the product should be evaluated, including risk analysis. The need for and the extent of re-qualification and re-validation should be determined and the rationale captured in the documentation.
Basic Components of a Change Management System
If a piece of equipment or a process needs to be modified, it should follow an established and approved change control process as outlined in a detailed approved procedure. This procedure should include direction and guidance and answer the following questions:
Ø What is the proposed change?
Ø How will it be implemented?
Ø Who are the necessary parties to approve it?
Ø How will it be tested or validated once the change has been made?
Ø What is the rationale for the change?
Ø What is the timing of the change?
Ø What is the impact to quality once the change is implemented?
A change management request should be issued and circulated to designated parties to review and approve the change.
Each site should have a formal and documented change management system, which evaluates the effectiveness of each change proposed, defines clear roles and responsibilities and assesses the impact of change on the validation/stability and/or registration status of the change.
Audit Strategy
To determine the effectiveness of the change management program, one strategy is to identify a completed change that has taken place at the site and follow it through the change management process. Depending on the actual change, several GMP systems may be impacted.
The site’s change management program should be established as part of the Quality system.
Under the Quality system, the site’s requirements for change control should be described.
Any change made as part of the change management program should be:
Ø Documented
Ø Evaluated
Ø Approved
Ø Tracked to completion
Ø Assessed for impact
Ø Closed
If the change is a production change, within the production GMP system, it should be part of the change management system and assessed to determine if it requires validation, a stability study, communicated to or approved by the regulatory authorities. For each site or contractor, it is important to determine if the proposed change requires global approval.
Change Request
To initiate any type of change a change request must be generated. Minimum information that should be included is the following:
Ø A description of the proposed change including scope
Ø Where the change will take place
Ø The anticipated plan to include schedule for task completion and proposed date(s) of implementation
Ø Affected documents: specifications, methods, standard operating procedures
Ø Estimate of resources needed to bring about the change
Ø Justification/reason for the change
Ø Supplemental documents supporting the change
Ø Whether the change requires validation or stability studies
Ø Risk assessment of the change
Ø Date of submission of change form
Ø Regulatory assessments
Ø Implementation information (date, dependencies)
Ø Impact on product supply
Ø Multiple/cross-site Impact
Ø Assessment to packaging and labeling
Additional information may also be needed:
Ø A description of the status of the facility, process, equipment without the change
Ø Available alternatives for the change
Ø Approval by a global or executive group if the change will impact various sites and has worldwide ramifications.
Ø Any necessary documents, prints, studies, position/concept papers, data to support the change.
Ø Subsequent change assessment
Systems may require implementation information (i.e., date of change, first batch impacted, etc.) as part of the change documentation. Depending on the policy of the site, changes may be combined (“bundled”), for example, if multiple systems are impacted, the system changes may be bundled.
Change Approval
All changes that are GMP related are to be approved by a representative of quality assurance.
While it is responsible for approving all changes, Quality Assurance is not necessarily responsible for coordination of the change.
Approvals may vary based on the type, classification and the location of the change. The change must be evaluated to determine appropriate groups involved are informed and communicated about the change and are given appropriate information.
Change Coordinators and Initiators are usually the individuals who use the process or are impacted by the change and are usually the persons responsible to present and evaluate the change. They are responsible to provide the information associated with the proposed change. This includes providing clear, documented descriptions, assessments and providing clarifications if needed. In addition, they are responsible to determine appropriate approvers who would be applicable to evaluate the change from a regulatory impact, impact on validated systems and departmental impact.
Approvers should work with the Change Coordinators. Their responsibility is to evaluate and analyze the content of the proposed change, be sure the change and it’s technical aspects are clearly stated, that it involves the appropriate actions and is all inclusive of all processes/systems affected. They are expected to critique for clarity and state relevant comments. Approvers are those individuals with authority to accept or reject the change.
As an approver, they have three responsibilities. The first is that they accept the concepts, requirements and responsibilities within the change as they apply to their area. The second is that they verify the accuracy of all functions directly affecting their area of responsibility.
The last responsibility is to provide the required resources to facilitate implementation of the change, whether specific or implied.
If changes to the proposal document are needed prior to approval, the Change Coordinators, Initiators and Approvers should work together to facilitate. If during the review process a change is determined as not needed or additional changes or modifications to the proposal are warranted, the process may have to be reinitiated or require the generation of additional change requests.
Only after documented approval is attained can implementation of any change commence.
Change Implementation
The change as described in the approved request can proceed to implementation according to the plan. If needs for additional changes are encountered during the implementation process, that were not approved as part of the original proposal, then additional change request approvals may be necessary.
Assessment of the Change as Implemented
Procedures should be in place to evaluate and assess implemented changes. The intention is to provide confirmation the original change had the intended effect based on the original justification. For a minor or evident change the assessment can be performed as part of the implementation process. However, for changes that are wider in scope and impact, the assessment could be done initially and/or after appropriate data points are available (based on data generation).
Change Closure
The change request is closed when the change has been implemented, documentation updated, outstanding actions completed, follow-up assessments performed and concluded as effective, and regulatory commitments have been communicated.
Summary
Any change that affects a GMP system or the regulatory compliance of a product or process is to be controlled through a formal approved change control system/process. The change control system should include information from the submission, through to the implementation and effectiveness assessment of the change.
A representative of the Quality unit must approve proposed changes that have the potential to have an impact on the quality, purity, identity, and safety of a drug product. All changes that have regulatory impact must be reviewed and assessed with respect to the product submission by Regulatory personnel.
Changes are usually categorized and tracked. Depending on the site criteria, changes may be prioritized differently and be subjected to different types of implementation strategies, as well as proposal and approval. Quality unit involvement should be early on in the process, through to final closure.
Key Parameters in Auditing a Change Management System
Prior to the Audit
Review the inventory list of the site’s critical equipment, instruments and systems and determine if there have been changes to them.
Determine if there are any outstanding corrective actions from either internal audits or regulatory inspections involving change management.
During the Audit
Ensure that any change made to facilities, equipment, materials, processes, documents or informational technology is part of a site’s change management program.
Ø Verify that there is a written policy, guidance or procedure in place that identifies all aspects of the change management program.
Ø If more that one change management system exists, determine what system governs what type of change and how they are connected..
Ø Determine if the site has different levels of changes.
Ensure that there is a procedure that identifies the activities for each level of change. Ensure that there is appropriate documentation for each level of change.
Ø Determine if there is a standard method of approval for documents and that the approval process is documented.
Ø Ensure that if changes are made to the proposed original change after the review process, that the revised changes are documented.
Ø Verify that GMP changes are approved by the Quality group.
Ø Verify that no change, with potential regulatory impact, is implemented until it has been approved by regulatory affairs.
Ø Verify that changes requiring regulatory approval do not progress prior to receiving regulatory approval.
Ø Ensure that there is a list of approvers or approver titles for various levels of change.
Ø Ensure the supplier or contractor as part of the change management process include a step for approval or notification to the sponsor company of changes to manufacturing, specification or testing requirements
Ø If approvers have delegated their authority to another individual, ensure that there is a memo reflecting this.
Ø Ensure that if changes are made to the change approval process that they are documented.
Ø Ensure that there is a method to coordinate a change in all affected documents.
Ø If the same product is produced at multiple sites, determine how each site is notified and the change is implemented.
Ø If a change has been made to an electronic system, ensure that training on the system has taken place.
Ø Determine what the site’s procedure is on bundling changes.
Ø Verify that the status of changes is tracked and accessible.
Ø Determine if there is more than one level of approving bodies for a change, e.g. global changes.
a. Determine who the approvers are at each level.
b. Determine the criteria for approvals at more than one level.
Ø Ensure that before implementation of a change requiring regulatory affairs approval takes place, it has been approved by regulatory affairs
Verify that the user area is formally notified of the approval.
Ensure that all personnel are trained on the change being effected, if appropriate.
Ø Verify that all training is documented.
Ø Verify temporary employees and consultants are trained if working on or with equipment or processes that have changed.
Review the Quality System.
Ø Verify that there is an established and approved Quality System/Quality Policy that is endorsed by management.