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.
21 CFR 211.100(a)
Changes to Procedures Not Reviewed, Approved
Changes to written procedures are not [drafted, reviewed and approved by the appropriate organizational unit] [reviewed and approved by the quality control unit]. Specifically, ***
21 CFR 211.160(a)
Lab controls established, including changes
The 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, ***
21 CFR 212.20(c)
Adverse effects of changes made
You did not demonstrate that any change does not adversely affect the [identity] [strength] [quality] [purity] of your PET drug. Specifically,***
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:
21 CFR 820.30(i)
Design changes – Lack of or Inadequate Procedures
Procedures for design change have not been [adequately] established. Specifically,***
21 CFR 820.40(b)
Document change records, maintained.
Records of changes to documents were not [adequately] maintained. Specifically, ***
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, ***
21 CFR 820.75(c)
Process changes – review, evaluation and revalidation
A validated process was not [reviewed and evaluated] [revalidated] when changes or process deviations occurred. Specifically, ***
21 CFR 820.40(b)
Change records, content
Records 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, ***
21 CFR 820.50(b)
Supplier notification of changes
There is no agreement with [suppliers] [contractors] [consultants] to notify you of changes in the product or service. Specifically, ***
21 CFR 820.75(c)
Documentation – review in response to changes or deviations
There is no documentation of the [review and evaluation of a process] [revalidation of a process] performed in response to changes or process deviations. Specifically, ***
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.
Today I spoke at the ASQ Lean and Six Sigma Conference on sustaining change. Great crowd (though I felt bad for the folks sitting on the floor) and the session has spawned a bunch of great conversations that I hope continues in the future.
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.
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).
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
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.)