In this slide contains Investigation, reason, case study of OOS.
Presented by: K Venkatsai Preasad. (Department of pharmaceutical analysis and quality assurance).
RIPER, anantapur.
Pests of safflower_Binomics_Identification_Dr.UPR.pdf
Case study on Out of Specification (OOS).
1. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 1
A Seminar as a part of curricular requirement
for I year M. Pharm I semester
Presented by
K.VENKATASAIPRASAD. (20L81S0402).
M.PHARM
Department of Pharmaceutical Quality Assurance.
Under the guidance/Mentorship of
Dr. P. Ramalingam., Ph.D.
Director- R&D Division,
Professor of pharmaceutical analysis
and medicinal chemistry
CASE STUDY
ON
OUT OF SPECIFICATION(OOS)
2. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 2
S.NO CONTENT
1
Introduction
2
Reason for OOS
3
OOS investigation
4
Case study 1
5
Outcomes
6
References
Content Table
3. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 3
OOS(OUT OF SPECIFICATION):
The term OOS results includes all test results that fall outside the
specification or acceptance criteria established in drug applications,
drug master files, official compendia, or by the manufacturer.
TWO MAOR ISSUES:
• What test results?
• What specifications?
Introduction
4. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 4
• There are lot of guidelines are available for defining and handle the
OOS products/materials/batches as:
MHRA guideline for OOS
CDER guideline for OOS
PIC/S guideline for OOS
5. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 5
• The OOS may be observed during the analysis of:
Stability study
Finished API
Intermediates
In-process
Raw materials
Packing materials
6. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 6
• OOS found due to the following reasons but not limited to:
Reasons
OOS
Laboratory
errors
Process
Related
Sample
homogeneity
7. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 7
Laboratory errors:
•Laboratory errors
Method of
analysis
Use of non
calibrated
instruments
Error in
calculation
Analyst
error
Instrument
failure
8. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 8
Process related:
•Process related
Operator
error
Equipment
failure
Deviation
from the
validated
procedure
Quality of
raw material
or
intermediate
used
In-process
control
during
manufacturi
ng
9. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 9
Sample homogeneity:
•Sample homogeneity
Sampling error
Handling of
sample
Pooling of
sample
10. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 10
OOS investigations
As per MHRA(EU GMP) As per CDER(US FDA)
Phase - I Investigation
(Primary &extended lab
investigation)
Phase - II investigation
(Manufacturing investigation)
Phase - III Investigation
(Extended manufacturing, Re-
sampling and re-analysis)
Phase - I Investigation
(Primary & extended lab
investigation)
Phase - II investigation
(Manufacturing investigation and
re-sampling and re-analysis)
11. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 11
12. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 12
Case study 1
13. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 13
The law:
Under the Federal FDC Act
drug is adulterated
if the methods/facilities/controls used for, its manufacture,
processing, packing or holding
do not conform/not operated in accordance with cGMP to
assure that the drug meets the requirements to safety, identity,
strength, quality and purity characteristics.
(21 U.S.C. § 351(a)(2)(B) )
14. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 14
• FDA Inspection:
FDA investigators conducted a general inspection of Barr's
Northvale facility during August and September 1989 as well
as separate general inspections of Barr's Northvale and
Pomona facilities from May to September 1991.
After each inspection, the investigators issued Forms 483
(Inspectional Observations).
15. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 15
The 1989 Form 483, which contained five general
observations, cited Barr for
Invalidated manufacturing processes
Invalidated cleaning processes
The lack of failure investigations
Incomplete annual reviews
Failure to explain retesting
16. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 16
• The Offense:
Barr Laboratories was accused of having breached GMP
guidelines by routinely re-testing, re-sampling and re-
processing, had effectively persuaded all pharmaceutical
industry laboratories to standardize their protocols for dealing
with out-of-specification results (OSRs).
The court did not accept the FDA submission that an OSR
necessarily meant a batch failure.
17. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 17
• Key Points: Essence of Barr Labs Decision
Release of batch:
• Testing must show satisfactory conformance to
specifications, including Strength of each active ingredient.
• Context and history of product and batches inform the final
conclusion.
18. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 18
• Lesson -Have a plan for OOS:
Don’t test into compliance
Have a policy and follow it…
Avoid repeat testing
19. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 19
Outcomes
OOS investigations can be time consuming, but are necessary.
Robust OOS investigation SOP is critical.
Need for employee training and understanding.
Investigation plans must be pre-defined.
Multiple departments may be involved.
Scientific rationale needs to be used at each step.
QA needs all data in order to make the right decision.
Implement CAPAs.
Testing into compliance is not good.
20. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 20
References
USA vs. Barr Laboratories, Inc. Civil Action No. 92-1744, US
District Court for the district of New Jersey, February 4, 1993.
FDA, CDER, “Guidance for Industry, Investigating Out of
Specification (OOS) Test Results for Pharmaceutical Production,”
September 1998.
Torbeck, L., “Reportable Values for Out-of-Specification Test
Results,” Pharmaceutical Technology, February 1999.
21. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 21
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