2020 FDA 483s around change

The yearly database of 483s has been updated by the FDA. Lots will be written on themes as we end the year, so I decided to give a few of my immediate observations.

I find that over time what I focus in on changes, as my jobs evolve and change, and the interests I have shift. However, some things never change, so let us talk change.

Reference NumberShort DescriptionLong Description2020 Frequency2019 Frequency2018 Frequency
21 CFR 211.100(a)Changes to Procedures Not Reviewed, ApprovedChanges to written procedures are  not [drafted, reviewed and approved by the appropriate organizational unit] [reviewed and approved by the quality control unit].  Specifically, ***8139
21 CFR 211.160(a)Lab controls established, including changesThe establishment of [specifications] [standards] [sampling plans] [test procedures] [laboratory control mechanisms] including any changes thereto, are not [drafted by the appropriate organizational unit] [reviewed and approved by the quality control unit].  Specifically, ***41817
21 CFR 212.20(c)Adverse effects of changes madeYou did not demonstrate that any change does not adversely affect the [identity] [strength] [quality] [purity] of your PET drug. Specifically,***111
483s related to changes

I think its fair to say the decreases as a result of the pandemic and the reduced inspections.

Over on the device side of things we see:

Reference NumberShort DescriptionLong DescriptionFrequency
21 CFR 820.30(i)Design changes – Lack of or Inadequate ProceduresProcedures for design change have not been [adequately] established.  Specifically,***26
21 CFR 820.40(b)Document change records, maintained.Records of changes to documents were not [adequately] maintained.  Specifically, ***6
21 CFR 820.70(b)Production and Process Change Procedures, lack of or Inad.Procedures for changes to a [specification] [method] [process] [procedure] have not been [adequately] established.  Specifically, *** 5
21 CFR 820.75(c)Process changes – review, evaluation and revalidationA validated process was not [reviewed and evaluated] [revalidated] when changes or process deviations occurred. Specifically, ***5
21 CFR 820.40(b)Change records, contentRecords of changes did not include [a description of the change] [identification of the affected documents] [the signature of the approving official(s)] [the approval date] [when the change became effective].  Specifically, ***



3
21 CFR 820.50(b)Supplier notification of changesThere is no agreement with [suppliers] [contractors] [consultants] to notify you of changes in the product or service.  Specifically, ***3
21 CFR 820.75(c)Documentation – review in response to changes or deviationsThere is no documentation of the [review and evaluation of a process] [revalidation of a process] performed in response to changes or process deviations.  Specifically, ***1
Device 473s around change

I’m a firm believer that pharma should always pay attention to the medical device side for 483s. A lot of us are combination products now (or will be) and there is always good trends to be aware of.

My key takeaways:

  1. Think change management and not just change control and document control
  2. Computer change controls need to be holistic and system orientated
  3. Have a process that ensures changes are appropriately reviewed and approved
  4. Risk based and evaluate validation
  5. A robust supplier management program is critical, plan for change

Here’s a more detailed checklist to help you evaluate your change system.

Understanding the Levers of Change

As part of my presentation “Sustaining Change – Executing a Sustainability Plan” at the ASQ Lean and Six Sigma Conference tomorrow I’ll be talking about levers of change.

Understanding the change landscape

Change Management practitioners usually talk about seven levers:

  1. Infrastructure – Investing in the tools, processes, and other resources that employees need to be successful with the change initiative.
  2. Walk the Talk – active leadership is about ownership; it includes making the business case clear, modeling behaviors, clearing obstacles and making course corrections.
  3. Reward and Recognition – acknowledgement and compensation for employees who work to move the initiative forward
  4. Mass Exposure – getting out information about the change through broadcast messages and other communication pathways
  5. Personal Contacts – creating opportunities for advocates to share their experience of the change with peers who feel disengaged
  6. Outside advocates – bringing in resources (internal or external) to gain expertise for the change initiative
  7. Shift Resisters – moving people to areas less affected by the initiative.
7 levers of change

Conference Speaking -2020 Lean and Six Sigma

In February I will be presenting at the 2020 ASQ Lean and Six Sigma Conference in Phoenix on Sustaining Change – Executing a Sustainability Plan.

Here’s the presentation summary:

For Lean and Six Sigma projects a central question should always be “how do we sustain this change?” Sustainability is a major part of all the major change models but is often the easiest to neglect. This session will engage the participant in building a Sustainability Plan, a key tool to ensure the change is anchored and embedded in the organization. Through three case study examples of changes at the three major change levels -transactional, organizational and transformational – the participant will gain the knowledge to create and execute an effective change plan.

During this session examples will be given for each component of a sustainability plan:

  • Communication: Mechanisms for persuasive communication and ongoing socialization of the change, rites of parting (saying goodbye to the old ways of doing things), and rites of enhancement (acknowledgment of quick wins and continued adoption)
  • Metrics Tracking: How to identify and execute consistent and effective ongoing measurement and results reporting to track progress and ensure sustained results • Performance Management: Process for observing and objectively measuring desired behaviors and attitudes, including performance appraisal process, promoting, demoting and transferring, and training and development
  • Rewards and Recognition: Program of intrinsic and extrinsic incentives to reinforce desired behaviors and attitudes
  • Sustaining Ownership: Consistent process for ensuring sustained ownership of the change through the ongoing transfer of experience and knowledge
  • Continuous Improvement: Mechanisms for responding to changing requirements and implementing improvements based on feedback, observations, and metrics

The following questions will be explored, and tools for finding answers will be provided:

  • How should organizational achievements reinforcing the change be commemorated
  • What behaviors should be observed and measured on a regular basis?
  • What results should be observed and measured on a regular basis?
  • What metrics should be used for measuring behaviors and results?
  • What mechanisms should be used for reporting results? • What criteria should be used to allocate rewards and promotion?
  • What mechanisms should be used for training, coaching, and role modeling?
  • What processes and procedures should be put in place to ensure sustained ownership of the change?
  • What continuous improvement mechanisms will address low adoption rates and ensure the change becomes part of the organization’s normal functioning?

At the end of the session the user will have a template for creating a sustainability plan and will have been provided tools to successfully execute the sustainability phase of a change.

Learning Objectives 1. Assess the role of sustainability in the major change management methodologies and apply to lean and six sigma projects. 2. Facilitate the sustainability phase of change management. 3. Compose a sustainability plan.

PIC/S on Change Review and Effectiveness

Starting from the end, let’s review some of the requirements in the new draft PIC/S guidance.

Prior to change closure

RequirementImportant Points
Changes meet their intended objectives and pre-defined effectiveness criteria. Any deviations from those criteria are adequately assessed, accepted and managed/justified. Whenever possible, quantitative data are leveraged to objectively determine change effectiveness (e.g. statistical confidence and coverage).Clearly delineating what effective means as a date is critical to generate data.

CQV activities can tell you if the intended objective is met. Effectiveness reviews must be made up of:

Sufficient data points, as described in the implementation plan, gathered to a described timeline, before an assessment of the change is made.

The success criteria should be achieved. If not, reasons why they have not been achieved should be assessed along with the mitigation steps to address the reasons why, including reverting to the previous operating state where appropriate. This may require the proposal of a subsequent change or amendment of the implementation plan to ensure success.

Data and knowledge gathered from implementation of the change should be shared with the development function and other locations, as appropriate, to ensure that learning can be applied in products under development or to similar products manufactured at the same or other locations
As part of the quality risk management activities, residual risks are assessed and managed to acceptable levels, and appropriate adaptations of procedures and controls are implemented.These are action items in the change control.

As part of the closure activities, revise the risk assessment, clearly delineating risk assessment in two phases.
Any unintended consequences or risks introduced as a result of changes are evaluated, documented, accepted and handled adequately, and are subject to a pre-defined monitoring timeframe.Leverage the deviation system.

Prior to or after change closure

RequirementImportant Points
Any post-implementation actions needed (including those for deviations from pre-defined acceptance criteria and/or CAPAs) are identified and adequately completed.If you waterfall into a CAPA system, it is important to include effectiveness reviews that are to the change, and not just to the root cause.
Relevant risk assessments are updated post-effectiveness assessments. New product/process knowledge resulting from those risk assessments are captured in the appropriate Quality and Operations documents (e.g. SOPs, Reports, Product Control Strategy documents, etc.)Risk management is not a once and done for change management.
Changes are monitored via ongoing monitoring systems to ensure maintenance of a state of control, and lessons learned are captured and shared/communicated.Knowledge management is critical as part of the product management lifecycle.

Lessons learned are critical.