Interim Controls within a Change Control

The PIC/S recommendation on change control section 5.3 “Change Planning & Implementation” recognizes that changes often address issues that need to be remediated:

  • Potential risks with the current state (until changes are implemented) and any risks that might be temporarily introduced during the change process are adequately assessed.
  • Interim controls (short-term measures), as needed, are identified and implemented in a timely manner to monitor/mitigate risks associated with the current situation (until change implementation).

This section also recognizes that changes introduce an interim set of conditions that lead to implementation – from opening a machine through massive construction activities, and just about anything else.

A good change control does not just address what is necessary to implement the desired future state. It also contains interim controls for managing the current state until the future is implemented, and addresses all of the potential risks during the process of implementation.

Change plans address current, interim, and future states

Often the change control stems from an action plan in a CAPA record, where the interim controls are specifically called out and detailed. These may be adequate for a relatively brief period but are not realistically sustainable. Remember that these interim controls must also go through the appropriate change control process. Which may have been a separate change control or be part of this change control. In all cases, the change control should either determine that the CAPA plan is adequate or identify additional risks that were identified during change planning.

Risk assessments for change control should really have three basic risk questions:

  • What are the risks of the current state as we implement the change?
  • What are the risks of the implementation process?
  • What are the risks of the future state?

As discussed elsewhere, these questions are really branching trees.

The Risk Question branches in changes

Interim controls in a change are usually little temporary changes in the change plan that either mitigate occurrence or impact.

Interim Control TypeMitigate OccurrenceMitigate Impact
ExamplesEvery record processed will be reviewed for the event error before completion. Revised preventive maintenance procedure to require vibration test at next preventive maintenance. Increase cleaning frequency of incubator.Add emergency response steps to address a valve that is malfunctioning. Add engineering check for pump prior to each use. Perform cleaning log review prior to use.

As temporary changes, it is important to determine how they will be implemented, if they require monitoring, and how they will go away. Often the process of implementation of the change removes the temporary changes, but that is not always the case.

Changes that impact multiple product

Dear all, regarding question 20 “Is the effective date of the change (completion date) recorded and when appropriate the first batch manufactured recorded?” we are not sure how to handle it for multi-product changes. At our site we manufacture products of different customers. Sometimes we have changes, where f.e. documents of several products need to be adapted. How are the requirements defined in such cases? Do we need to report the first batch only once or for each product

Correspondent

This request comes from my post “29 questions to ask about your change management/change control system.”

At heart, this requirement is to help meet the regulatory requirement that “After implementation, an evaluation of the change should be undertaken to confirm the change objectives were achieved and that there was no deleterious impact on product quality.” (ICH Q9 part IV.B.3.d)

In order to perform an evaluation, you must be able to know when to start. This evaluation must be able to be performed on each and every product. It is from here we can settle on 1st batch. There are lots of ways to do this. The requirement is, for each and every product, to be able to state definitively when the change was first applied to the product.

We can drill down to the most definitive guidance on GMP Change Control, the PIC/S Recommendation “How to Evaluate and Demonstrate the Effectiveness of a Pharmaceutical Quality System in relation to Risk-based Change Management” which further strengthens the requirement:

SectionRequirementMeans
5.4. Change Review and EffectivenessChanges are monitored via ongoing monitoring systems to ensure maintenance of a state of control, and lessons learned are captured and shared/communicated. (Note: Activities such as Management Review, Annual Product Quality Review, Continuous Process Verification, Deviation Management and Complaint Monitoring can be useful in this regard.)Having that definitive point allow all these activities to be effective.

The requirement is clear. We need to be able for any given change identify when it started impacting product.

All of the various Annual Product Review/Product Quality Review requirements also require the ability to evaluate all changes to the product in a given time frame.

There is also the need, for release purposes, to determine if a batch is impacted by a change.

Like many such requirements, there are multiple ways to do this. I think the requirement to capture first batch in a change control really stems from it, in many ways, being the easiest to do as you only have to manage it in the change control workflow. Though, in all honesty, it is also darn annoying with changes potentially being open more than a year to capture all possible products.

Based on our core requirement, there are several factors to consider:

  • There must be a way for a user to easily determine when a given change impacted a given product and to determine if a given batch was impacted by the changes
  • The user must be able to link any batch to all the changes that impacted it
  • The user must be able to run a report of all changes that impacted a product in a time frame

There are multiple ways of solving for this from the put a field in the change control to set of interfaces between the ERP and eQMS (and maybe MES).

Change Management is Bigger than Change Control So Think Beyond Individual Changes

As a pharmaceutical GXP professional with one foot in the GXP Quality camp and another in the organizational change management camp, I have a few pet peeves. And one of my biggest is whenever someone uses a phrase like “Change management may be known by different terminologies (e.g., change control, change requests, change orders).” That’s a reductionist statement that can really lead to a lot of confusion in an organization.

Change management is the how of change – assess, handle and release. Change control is the what, the execution steps. Change management is a big picture system that looks systematically at people, technology, process, and organization. Change control is the set of mechanisms for controlling the introduction of that change to the organization.

A lot of different systems and processes have change control elements. As many of these processes are supported with specific technologies, it can be very important to think about how they fit together like a puzzle.

This puzzle is usually made up of core requirements. Based on how much the change impacts them decides the rigor of the change control process.

Take for example a pharmaceutical manufacturing site. It is fairly typical to have one process for maintenance, another for IT, another for documents, etc. And then you have a change control system for things that impact established conditions, including validated state and regulatory submissions. Maybe you work at some technological utopia with a single system that manages all changes with all the deliverables, but at most places, you are trying to balance efficiency with effectiveness, and have a real need to avoid unnecessary duplication.

ICH Q12 helps by giving a nice breakdown of the major families of changes.

This helps somewhat, but for the average user it is not very specific. We need to translate it. First, we establish that only one system will be used for regulatory impact (“Tell and Do”, “Do and Tell” “Do and Report” and some of “Do and Record”), then we put the major activities that go into it. This breakdown might look like:

We are utilizing a few major criteria:

  1. Impact of regulated state
  2. Impact of validated state
  3. Risk level of change
  4. Scale of change to the organization

Using these criteria we can even drill down further, for example:

FEU Changes as a flowchart

It is usually a good idea to go down to an even deeper level to help the end-user.

Requires CCR

Does Not Require CCR

Any change that impacts the integrity of controlled classified areas, including all room and equipment surfaces

 

Changes that do not impact integrity of controlled classified areas by meeting the following criteria:

·     Does not change airflow

·     Does not impact structural integrity and maintains a smooth cleanable surface

·     Does not change means of ingress/egress

·     Does not impact current sampling sites from the Environmental Monitoring Program

·     Materials used are resistant to cleaning agents used in the area as defined in the building specifications

·     Materials are included in disinfectant effectiveness study

Any change that impacts air balancing

Work that is part of routine or preventive maintenance or calibration

Changes to equipment or replacements with a functional equivalent or different component

Changes to equipment with an exact component

Changes to facility floor layout

Instrument calibration including adjustments to field instrumentation

Changes to equipment operating and control parameters

Removal/storage of portable equipment

Changes to equipment, material and personnel ingress, egress and flow procedures

Replacement of system instrument hardware with exact components (hardware)

Changes to room classifications

Engineering studies that do not change the validated state or change anything requiring a CCR per this procedure

Changes that impact the environmental integrity of a room

Alarm set point changes that return to the previous qualified/validated state

Replacement and/or decommissioning of equipment, utilities or facilities

Remediation work (such as mechanical polishing, weld repairs, electro-polishing, filling of pits, de-rouging and chemical cleaning with already approved material)

Alarm set point or classification changes

Addition, modification or deletion to Potable Water, Plant Steam, Chilled Water, Cogeneration System, or pre-treatment reverse-osmosis

Changes in intended use of a room or area

Modification to piping tied to Potable Water, Plant Steam, Chilled Water, Cogeneration System, or pre-treatment reverse-osmosis

Changes to Preventive Maintenance that includes:

·     Decreasing frequency of preventive maintenance (i.e. making less frequent)

·     Change in intent of a preventive maintenance task

·     Adding or removing tasks

Changes to Preventive Maintenance that include:

·     Increasing frequency of preventative maintenance (i.e. making more frequent)

·     Administrative changes

·     Adding clarity to a task (e.g. changing instructions on how to execute a task without altering the intent of the task)

·     Reordering task(s) without changing intent of the task(s)

·     Changes of tools needed to execute a task; room dedicated tools must remain in the designated area

·     Changes to quantity of materials

Changes that decrease the calibration frequency (i.e. make less frequent) for GMP Critical equipment (e.g. directly related to operational control of the product)

·     Changes that increase calibration frequency (i.e. make more frequent) for GMP Non-Critical equipment (e.g. indirectly related to operational control of the product)

Tuning parameter, adjustment to the gain, reset and rate of a PID controller

New or replacement analytical equipment or instruments identified as Category A or Category B-Calibration Only with an exact component

Changes to the calibration frequency of GMP critical equipment (e.g. directly related to operational control of the product)

Changes to manufacturing report properties

Changes to the Environmental Monitoring Program, including addition, deletion or change to a sample location

Changes to alarm paging/notification recipients

Changes to the program for disinfection of a facility or equipment exterior

Creating/modifying individual user accounts

Change of materials of construction or class of polymeric materials (e.g. elastomers, tubing, gaskets and diaphragms)

Add an instrument to the calibration system during pre-commissioning

Changes to hardware or infrastructure associated with a validated system, equipment or utility

Changes to requalification frequency that do not change the intended use or validated state of the equipment or utility

Upgrade of application software or operating system for validated systems, equipment or utility

Corrective changes to an SOP to align it to the validated state

Changes to an SOP to align it to the validated state with impact to one or more regulatory filings

A corrective change to alarm set points to align with the validated state

Creating user groups and/or modifying user group privileges as part of a larger process change associated with validated systems, equipment, or utilities

Addition of a new calibration standard to be used with a new type of instrument at the Alachua site

Creating user groups and/or modifying user group privileges associated with validated systems, equipment, or utilities

Changes to alarm paging/notification recipients

Addition of a new calibration standard to be used with a new type of instrument at the Cambridge and Lexington sites

 

Modifying a phase prompt or message associated with validated systems, equipment, or utilities

 

Addition / change of a graphic associated with validated systems, equipment, or utilities

 

Addition or changing an interlock/permissive trigger

 

Addition/removal of I/O of validated systems

 

Changes to the Environmental Monitoring Program, including addition, deletion or change to a sample location

 

Changes to alarm paging/notification functionality

 

Historical data collection configuration

 

Change of equipment and spare parts storage site, including transfers between facilities and transfers to a contracted third party

 

 

All of this is change management. We utilize multiple change control mechanisms to manage the change.

Also, don’t forget that change controls can nest. For example a change to the EQMS has IT changes, document changes, training changes, and probably more.

Implementing a Quality Ambassador Program

Quality ambassadors can influence their peers to prioritize quality, thereby strengthening the culture of quality in the organization. Quality leaders can use this guide to develop a quality ambassador program by identifying, training, and engaging ambassadors.

Utilizing Kotter’s eight accelerators for change, we can implement a Quality Ambassador program like this:

AcceleratorActions
Create a strong sense of urgency around a big opportunityDemonstrate the organizational value of Ambassadors by performing a needs analysis to assess the current state of employee engagement with quality.
Build and evolve a guiding coalitionBring together key stakeholders from across the organization who will provide input in the program’s design and support its implementation.
Form a change vision and strategic initiativesIdentify the key objectives for implementing a Quality Ambassador program and outline the lines of effort required to successfully design and pilot it.
Enlist a volunteer armyReach out and engage informal leaders at all levels of the organization. Find your current informal Ambassadors and draw them in.
Enable action by removing barriersBe vigilant for factors that impede progress. Work with your Ambassadors and senior leaders to give teams the freedom and support to succeed.
Generate and celebrate short-term winsPilot the program. Create success stories by looking at the successful outcomes of teams that have Quality Ambassadors and by listening to team members and their customers for evidence that quality culture is improving. Your goal will be to create an environment where teams that do not have Quality Ambassadors are asking how they can participate.
Sustain accelerationScale the impact of your program by implementing it more broadly within the organization.

Define the Key Responsibilities of Quality Ambassadors

  
What activities should Quality Ambassadors focus on?  Example: Reinforce key quality messages with co-workers. Drive participation in quality improvement projects. Provide inputs to improve culture of quality. Provide inputs to improve and maintain data integroty
What will Quality Ambassadors need from their managers?    Example: Approval to participate, must be renewed annually
What will Quality Ambassadors receive from the Quality team?    Example: Training on ways to improve employee engagement with quality. Support for any questions/objections that ariseTraining on data integrity  
What are Quality Ambassadors’ unique responsibilities?    Example: Acting as the point of contact for all quality-related queries. Reporting feedback from their teams to the Quality leadership. Conveying to employees the personal impact of quality on their effectiveness. Mitigating employee objections about pursuing quality improvement projects. Tackling obstacles to rolling out quality initiatives
What responsibilities do Quality Ambassadors share with other employees?    Example: Constantly prioritize quality in their day-to-day work  
Expected time commitment    Example: 8-10 hours/month, plus 6 hours of training at launch

Metrics to Measure Success

Type of MetricsList of MetricsDirect Impact of Ambassador’s workRecommendations
Active Participation LevelsPercentage of organizational units adopting culture of quality program.
The number of nominations for quality recognition programs. Quality observations were identified during Gemba walks. Participation or effectiveness of problem-solving or root-cause processes. The number of ongoing quality improvement projects. Percentage of employees receiving quality training  
HighAmbassadors should be directly held responsible for these metrics
Culture of Quality AssessmentsCulture of quality surveys. Culture of quality maturity assessmentsMediumThe Quality Ambassador program is a factor for improvement.
Overall Quality PerformanceKey KPI associated with Quality. Audit scoresCost of poor qualityLowThe Quality Ambassador program is a factor for improvement.

Engaging for Quality

When building a quality organization, we are striving to do three things: get employees (and executives) to feel the need for quality in their bones; get them to understand what quality is and why it is important; and build the process, procedure, and tools to make quality happen. Practitioners in change management often call this heart, head, and hands.

Engage the heart, head and hands to build a quality culture

In our efforts we strive to answer give major themes of questions about why building a culture of quality is critical.

ThemeQuestions
WhyWhy do we need quality? Why is it important? What are the regulatory expectations? What happens if we do nothing?
WhatWhat results are expected for our patients? Our organization? Our people? What does out destination look and feel like?
HowHow will we get there? What’s our plan and process? What new behaviors do we each need to demonstrate?
YouWhat do you need to fulfill your role in quality? What do we need from you?
MeWhat do I commit to as a leader? What will I do to make change a reality? How will I support my team?
Five Themes of Change

The great part of this is that the principles of building a quality culture are the same mindsets we want embedded in our culture. By demonstrating them, we build and strengthen the culture, and will reap the dividends.

Be Preventative: What actions can be taken to prevent undesirable/unintended consequences with employees and other stakeholders. We do this by:

  • Involving end-users in the design process
  • Conduct risk assessments and lessons learned to predict possible failures
  • Ensure the reason for change is holistic and accounts for all internal and external obligations
  • Determine metrics as soon as possible
  • Focus on how the organization is responding to ongoing change
  • Think through how roles need to change and what employees need to be accountable for

Be Proactive: What actions can be taken to successfully meet objectives?

Be Responsive: What evidence-based techniques can be used to respond to issues, including resistance?

This is all about leveraging the 8 change accelerators and effectively developing strategies for change.