Presentation on Pharmaceutical Deviation, OOS & OOT.

1. DEVIATION
OOS, OOT
Vikas Chauhan
M.Pharm (PQA)

2. Sponsorship Deck
Table of Content
01 02 03 04
05 06 07
DEVIATION IN
PHARMACEUTICAL
INDUSTRY
REGULATORY
EXPECTATION
DEVIATIONS
TYPES
DEVIATION
CLASSIFICATION
CATEGORIES
OUT OF
SPECIFICATION
PROACTIVE
APPROACHES
TO MINIMIZE
OOS
OUT OF
TREND
08 09 10
TYPES OF
OOT
OUT OF TREND
IDENTIFICATION
AND
RESOLUTION
ANNEXURES
FOR OOT
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3. Deviations in the
Pharmaceutical Industry
what damage, if any ,
the product might have
suffered.
FORMAT
When a deviation occurs,
the responsible company
is required to conduct an
investigation to ascertain
what went wrong and
SOP
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4. Sponsorship Deck
Regulatory Expectation
"Any unexplained discrepancy...shall be thoroughly
investigated...The investigation shall extend to other
batches...that can have been associated with the
specific failure or discrepancy. A written record of the
investigation shall be made and shall include the
conclusions and follow-up
21 CFR 211.192
Any deviations from instructions or procedures should
be avoided as far as possible. If a deviation occurs, it
EC Guide to GMP
, should be approved in writing by a competent
Chapter 5 (5.15) person..."
Any significant deviations [from defined procedures
and instructions] are fully recorded and investigated
Any deviation from established procedures should be
documented and explained. Critical deviations should be
investigated, and the investigation and its conclusions
should be documented.
ICHQ7A
4

5. Planned Deviations
A deviation is any unwanted event
that differs from the approved
processes, procedures, instructions,
specifications, or established
standards. Deviations can occur
during the manufacturing, packing,
sampling, and testing of drug
products
GMP requires deviations to
be documented.
Assists With Continuous Improvement
• Planned deviations are temporary deviations from an existing
protocol or process that have been pre-approved.
• They are limited to a specific time period or a number of batches.
• Your organization makes these changes to avoid a potentially
hazardous situation.
• Deviations are planned in such a way that they do not compromise
the safety and efficacy of your products.
Examples of planned deviations in the pharmaceutical industry:
• Change in batch size due to reduced availability of raw materials
• Change in batch size for a specified number of batches
• Change in supplier for excipients
Un-Planned Deviations
• Unplanned deviations are also known as uncontrolled events,
unplanned events, or incidents.
• Unplanned deviations are non-compliances from your designed
protocols or systems at any stage of the lifecycle of a product
manufacturing, testing, holding, packaging, or storage.
Examples of Unplanned deviations in the pharmaceutical industry:
• Interruption of power supply resulting in equipment breakdown.
• Accident at the site due to human error.
• Disruption of utility services
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6. Deviation Classification Categories
MAJOR
DEVIATION
moderate to a considerable
impact on product quality or
GMP system.
• 20 working days
• Equipment breakdown
during processing.
• Raw materials received in
damaged cartons.
• Major variance from a
standard output range.
CRITICAL
DEVIATION
significant impact on the
production quality or GMP
system.
• 15 working days.
• Protocols not followed
during manufacturing.
• Use of contaminated raw
materials.
• Failure of the HEPA filters
in the cleanroom.
DEVIATION
MANAGEMENT
MINOR
DEVIATION
not have any direct impact
on the quality of the product
or the GMP system.
• 30 working days.
• Errors in the documentation
that do not affect data integrity.
• Spillage of a product during the
dispensing process.
• Free samples printed with a
price tag
(eQMS)
Electronic Quality
Management System
Close Event Track, Trend
If a Trend,
Trigger
Investigation
Develop
investigation
plan
Identify casual
factor
CAPA and
Effectiveness
check
Investigate
Assess and
classify risk
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7. Out-of-Specification (OOS)
When the results of a drug substance or drug product fall
outside the predetermined specification or defined established
criteria by the manufacturer or by the laboratory then it is
called Out of Specification (OOS).
Laboratory
Process
related
Sample
Homogeneity
INVESTIGATION
As
per
CDER
(US
FDA)
Phase-1 Laboratory Investigation
Laboratory investigation is related to
the Quality control department along
with rechecking of documents with
same analyst and re-testing with
different analyst with original sample.
Phase – II Investigation:
Manufacturing investigation Process
related investigation is to be carried
out by Production department along
with re-sampling and re- analysis.
Laboratory
Method of
Analysis
Use of Non
Calibrated
instrument
Error in
calculation
Analyst error
Instrument
failure
Process
related
Operation error
Equipment
failure
Deviations from
the validated
procedure
Quality of raw
material/
intermediate
used
In-process
control during
manufacturing
Sample
Homogeneity
Sampling error
Handling of
samples
Pooling of
sample
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8. Proactive approaches
to Minimize OOS Good analytical
methods –method
development/valid
ation/ transfer
Recurring problems
are reviewed in a
timely manner.
OOS/OOT are
reviewed,
investigated and
resolved ASAP
Internal audits
Data are reviewed
in a timely manner
and trended.
Sample flow is
clear and
documented
Follow SOPs
Follow Methods
Training Program
& Experience
Analysts &
Supervision
The OOS process is not applicable for In- process testing while trying to achieve a
manufacturing process end-point, i.e.: - adjustment of the manufacturing process. (e.g. pH,
viscosity), - for studies conducted at variable parameters to check the impact of drift (e.g.
Process validation at variable parameters).
Equipment /
Methods/ Analysts
8
Good
Documentation
Practices

9. Trend
Trend is a sequence of time related events. It
shows the general direction towards which a
particular situation/data is moving.
Trending
Trending refers to the techniques of data
collection, Good trending reflects
manufacturer’s profound knowledge of the
process and thus build confidence in the
manufacturer’s quality risk management.
Trend Analysis
Trend analysis is the widespread practice of
collecting information and attempting to
spot a pattern.
OUT-OF-TREND
01
03
02
For the Pharmaceutical Industry, the microbiological, chemical,
instrumental, and physical analysis of the raw materials and
finished goods samples generates a large amount of informative
data from the Quality Control Labs. Pharmaceutical companies
generally use QC Sample OOT (Out of Trend) to ensure that the
products meet the laid down specifications complying with FDA
21 CFR Part 11, EU Annex 11, cGMP
, GMP, and other
international and national manufacturing standards. A case of
Out of Trend must be investigated when sample results differ or
deviate from the sample’s historical results though they may be
within specifications.
How is the Pharmaceutical industry
benefitting from OOT
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10. Type of Out of
Trend (OOT)
Process Control Alert
A succession of stable information
factors or successive batches of
finished merchandise suggests a
strange sample.
Analytical Alert
When a single result
is aberrant but within
specification limits,
like out-of-trend
assay value.
Compliance Alert
Is the potential for OOT
results to occur before the
expiry date of the product
within the stability study on
the same product.
101

11. Out Of Trend (OOT)
Identification And
Resolution.
OOT
Identification
OOT
Determination
OOT
Verification
Stability
Prediction
New Time
Point Data
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12. ANNEXURES
Annex. No. 01 Format for
Out of Trend Investigation
Report
Annex. No. 02 Format for
Out of Trend Investigation
Log
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13. Thank
You
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