Download Forms Don FDA Deviation Investigations 2008

7/27/2019 Download Forms Don FDA Deviation Investigations 2008

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DEVIATION

INVESTIGATIONS

A Proper Objective Perspective

FDA USP Conference

Irvine, CA

December 5, 2008


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Investigations

Deviations (All departments)

Out-of-Specification (QC Lab) Out-of-Trend (QC Lab)

Raw Materials

Components

Containers/Closures

API

Finished Drug Product


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Deviations

Associated with limits vs. specifications

GMP mistakes or errors

Reprocessing or Rework

Unapproved changes

Performing an activity without proper training

Outside of operating parameters or in-processcontrol limits

Failure to follow written SOPs or approvedbatch record instructions


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Deviations

GMP mistakes or errors

Good documentation errorsmissing entries,

unexplained entries, improper corrections or editsto official records

Environmental Monitoring over alert or actionlimit excursions

Out of calibration

Unplanned preventive maintenance or repairs toqualified equipment or systems


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Deviation Investigations

Root Cause(s)Thorough Investigations

What vs. Why or How

The 20 : 80 (what : why/how) Rule

Corrective Actions

Batch release dependent

Preventive Actions

Batch release independent


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Deviation Investigations

Deviation investigations must not be biased fromthe startFrom an FDA or cGMP perspective, the purpose of

conducting a deviation investigation is not to release thebatch.

The true purpose of a deviation investigation is to determine the root cause for the deviation\

implement appropriate and meaningful corrective actions, and evaluate the implicated system (e.g., the training program) once

a pattern of repeating deviations is noted.


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Deviations Investigations

vs. Batch Release

(Product Impact Assessments)

Batch release should be considered a separate and distinct QA

function and activity!

Product Impact Assessments should be done collectively(summation of all deviations) after an appropriate deviationinvestigation has been completed.

All deviations must then be collectively evaluated at the timeof final batch release.


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Deviations

Root Cause(s)

Documenting all attempts to identify, determine,

confirm, or rule out potential root cause(s) Why and how did it occur

Detailed descriptions (what, where, when, andwho) of the deviation vs. root cause investigation

or assessments Definitive or Potential Root Cause(s)


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Root Causes

Definitive vs. Potential Root Causes

THERE IS A BIG DIFFERENCE BETWEENWHAT HAPPENED VS. WHY OR HOW

SOMETHING HAPPENED!


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Corrective Actions

Short term, immediate actions taken to corrector address the potential root cause(s) for each

reported deviation Actions designed to eliminate or minimize the

potential for recurrence of the deviation

Must be initiated (accountability in a formal

quality system) or completed prior to closing outof the investigation

Corrective actions should be tracked and trendedin a quality system


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Corrective Actions

General FDA 483 Observation

Corrective actions do not match or support

definitive or potential root causes.


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Deviations

Preventive Actions Longer term actions designed to determine the

effectiveness of corrective actions

Actions designed to ensure the prevention or

recurrence of deviations

Preventive actions do not have to be initiated or

completed prior to closing the investigation Preventive actions should be tracked, monitored

for completion, and trended in a quality system


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Preventive Actions

Preventive actions must focus on systemevaluations and system level continuous

improvement.

Quality system improvement is more important

to FDA than corrective actions (band-aid fixes

necessary to just release a batch).


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DeviationsFDAs Chronologic Expectations

Deviation reported in real time

Timely notification of QA (within 24 hours)

Thorough root cause investigation

Timely investigation (within 30 days)

Corrective actions proposed and initiated or completed

Investigation closed Implicated batch(es) released or rejected

Preventive actions initiated and closed


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Planned Deviations

Planned deviations should be handled through theQA approved change control procedures.

All changes should be evaluated for product

impact, significance The need for requalification or revalidation

Changes ultimately approved or rejected by QA.

QA should insist that planned deviations not beused; all deviations should be unintentional,unplanned, or unexpected.

Shutdown or validation protocols can also be usedin lieu of planned deviations.


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Deviation vs. Out of Specification

Preliminary investigation

Purpose: Investigate to determine if the initial OOS test

result is valid or invalid based on a review of the bench;do not discard sample preparation, pipettes, etc.

Analyst error

Sample preparation error

Instrument error

Reference standard

Calculation error

Failure to follow test method


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Deviation vs. Out of Specification

Once confirmed, invalid OOS test results

should be converted to deviation

investigations Confirmed valid OOS test results should be

investigated through the OOS procedure

Link to the failure investigation procedure forrejected materials, API, and/or finished product


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Deviation Management

Business Perspective Measures of efficiency and productivity

Qualified suppliers

Higher yields Process Optimization

Routine global senior management visibility Competitive business strategic plans

QA quality systems evaluation

Regulatory insurance policy (CGMPs) Mission or Vision Statements

Do it right the first time

Quality First


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Final Thoughts

Deviation investigations are not an unusual orforeign concept to industry or in our normaloutside of work life

Workers compensation or injury at work Consider steps taken with respect to EHS (safety or

injury related) investigations, corrective action, andpreventive action program.

Corrective actions are designed to target root cause(s). Preventive actions are designed to ensure corrective

actions are effective in avoiding work related injuriesthrough appropriate system level improvements.


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Contact Information

CDR Jeffrey T. Yuen, MPH, MBA

PresidentPrincipal Consultant

Jeff Yuen and AssociatesP.O. Box 6026

Orange, CA 92863-6026

Phone: 714 282-1014

E-Fax: 240 597-8351

E-mail: [email protected]


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Reproduction or Copies

Further reproduction, copies, or use of this presentationwithout explicit permission from Jeff Yuen and

Associates is strictly prohibited.

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Download Forms Don FDA Deviation Investigations 2008