m.pharm analysis, pharmaceutical analysis, food analysis, cosmetic analysis and evaluation, modern bio analytical techniques, advanced pharmaceutical analysis, phamaceutical validation

1. IMPURITIES IN NEW DRUG
SUBSTANCE
Submitted To:
DR. C. SREEDHAR
PROFESSOR AND HOD
DEPT. OF PHARMACEUTICAL
ANALYSIS
KARNATAKA COLLEGE OF
PHARMACY
BANGALORE
SUBMITTED BY:
S.GOKULRAJ
M PHARM 1ST SEMESTER
DEPT.OF PHARMACEUTICAL
ANALYSIS
KARNATAKA COLLEGE OF
PHARMACY
SUBJECT: APA
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2. CONTENT
KARNATAKA COLLEGE OF PHARMACY
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 INTRODUCTION
 DEGRADATION PRODUCTS
 RATIONALE FOR THE REPORTING AND CONTROL
OF DEGRADATION PRODUCTS
 ANALYTICAL PROCEDURES
 REPORTING DEGRADATION PRODUCTS
CONTENT OF BATCHES
 LISTING OF DEGRADATION PRODUCTS IN
SPECIFICATION
 QUALIFICATION OF DEGRADATION PRODUCT

3. INTRODUCTION
Objective:
 The objective of the guideline makes
recommendation to applicant on the content and
qualification of impurities in new drug products
produced from chemically synthesised new drug
substance.
RATIONALE
 Identification and characterisation of all degradation
products.
 Essential for achieving the quality in pharmaceutical
products.
 Development for patient safety.
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4. DEGRADATION PRODUCTS
 Unwanted chemicals that develop during the
manufacture, transport, and Storage of drug
products.
 Affect the efficiency of pharmaceutical products.
 --light
 --temperature
 -- pH
 Types of degradation products:
 Physical degradation products
 Chemical degradation products
 Microbiological degradation products
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5. RATIONALE FOR THE REPORTING AND
CONTROL OF DEGRADATION PRODUCTS
 Degradation products observed during
manufacture and/or stability studies.
 It should be-sound scientific appraisal of potential
degradation pathways.
 Impurities arising from the interaction with
excipients and/or the immediate container closure
system.
 A rationale should be provided for exclusion of
those impurities that are not degradation products
(e.g., process impurities from the drug substance
and impurities arising from excipients).
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6.  Laboratory studies conducted to detect
degradation products.
 Any degradation product observed in stability
studies recommended storage condition should
be identified at a level greater than (>) the
identification thresholds.
 Analytical procedures should be developed for
degradation products which are:
 --potent
 --toxic
 -- pharmacological effects.
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7. ANALYTICAL PROCEDURES
 The registration application documented evidence
(analytical procedure have been validated detection
and quantification of degradation products).
 Analytical procedure should be validated to
demonstrate specified and unspecified degradation
product.
 For validation, the samples should be stored under
stress condition like
 Light
 Heat
 Humidity
 Acid base hydrolysis
 Oxidation
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8. REPORTING DEGRADATION PRODUCTS CONTENT
OF BATCHES
 Clinical safety and stability testing.
 Quantitative results should be presented
numerically, and not in general terms such as
"complies", "meets limit”.
 Below 1.0%, the results should be reported to the
number of decimal places (e.g., 0.06%) in the
applicable reporting threshold
 Above 1.0%, the results should be reported to
one decimal place (e.g., 1.3%).
 Degradation products should be designated by
code number (e.g.. Retention time).
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9.  For each batch of the new drug product, the
documentation should include:
 Batch identity, strength, and size
 Date of manufacture
 Site of manufacture
 Manufacturing process
 Immediate container closure
 Degradation product content, individual and total
 Use of batch (e.g., clinical studies, stability studies)
 Reference to analytical procedure used
 Batch number of the drug substance
 Storage conditions for stability studies
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10. LISTING OF DEGRADATION PRODUCTS IN
SPECIFICATION
 Specification should contain a list of degradation
products.
 Characterise the degradation products stability
studies, knowledge of degradation pathways,
product development studies, and laboratory
studies.
 Selection of degradation product should be based
on the degradation products found in batches.
 Specified degradation products can be identified
or unidentified.
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11. NEW DRUG PRODUCTS SPECIFICATION SHOULD
INCLUDE
 Each specified identified degradation product
 Each specified unidentified degradation product
 Any unspecified degradation product with an
acceptance criterion of not more than (<) the
identification threshold.
 Total degradation products.
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12. QUALIFICATION OF DEGRADATION PRODUCT
Qualification :
 acquiring and evaluating data that establishes
the biological safety of an individual degradation
product.
 Degradation product present in a new drug
product adequately tested in safety and/or
clinical studies qualified.
 Degradation products that are also significant
metabolites present in animal and/or human
studies are generally considered qualified.
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13.  Degradation products could be considered
qualified at levels higher than those administered
in safety studies based on a comparison between
actual doses given in the safety studies and the
intended dose of the new drug product.
 Justification of such higher levels should include
consideration of factors such as:
 The amount of degradation product administered in
previous safety and/or clinical studies and found to
be safe.
 The increase in the amount of the degradation
product.
 other safety factors.
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14. Reporting Threshold:
A limit above (>) which an impurity should be
reported.
Identification Threshold:
A limit above (>) which an impurity should be
identified.
Qualification Threshold :
A limit above (>) which an impurity should be
qualified
MAXIMUM DAILY
DOSE
REPORTING
THRESHOLD
IDENTIFICATION
THRESHOLD
QUALIFICATION
THRESHOLD
< 2g/day 0.05% 0.10% or
1.0 mg per day
intake (whichever
is lower)
0.15% or
1.0 mg per day
intake (whichever
is lower)
> 2g/day 0.03% 0.05% 0.05%
THRESHOLD
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17. THANK YOU
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