1.3.
2 ICH guidelines:
According to ICH guidelines, each impurity must be investigated with respect to both
chemistry and safety aspects. The former include identification (structural
characterization),
reporting and quantitation using suitable analytical procedures, while the latter
include a process
of acquiring and evaluating data concerning the biological safety of an impurity
(qualification).
Individually listed impurities, limited with specific acceptance criteria, are referred to
as
specified and they can be either identified or unidentified.
Unspecified impurities are limited by a general acceptance criterion. A decision tree
for the
identification and qualification along with the corresponding thresholds, which are
dependent on
the maximum permitted daily dose (MDD), is given by ICH. Summing up, the
following list of
organic impurities must be presented in the specification of a synthetic drug
substance:
- Each specified identified or unidentified impurity
- Any unspecified impurity
- Total impurity
Specified unidentified impurities are referred to by an appropriate qualitative
analytical
description (e.g. relative retention time) [18].The ICH topics, codes of quality
guidelines are
given in Table 1.2
Table: 1.2: ICH topics, codes of quality guidelines
Topics / Code Quality guidelines
Q1A(R2) Stability Testing of New Drug Substances and Products
Q1B
Stability Testing: Photo stability Testing of New Drug Substances and
Products
Q1C Stability Testing for New Dosage Forms Annex to the ICH Harmonised
Tripartite Guideline on Stability Testing for New Drugs and Products
Q1D Bracketing and Matrixing Designs for Stability Testing of Drug
Substances and Drug Products
Q1E Evaluation of Stability Data
Q1F Stability Data Package for Registration in Climatic Zones III and IV
Q2(R1) Validation of Analytical Procedures: Text and Methodology
Q3A(R2) Impurities in New Drug Substances
Q3B(R2) Impurities in New Drug Products
Q3C(R4) Impurities: Guideline for Residual Solvents
Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the
ICH Regions
Q4B ANNEX 1 Evaluation and Recommendation of Pharmacopoeial Texts for Use in
the
ICH Regions on Residue on Ignition/Sulphated Ash General Chapter
Q4B ANNEX 2 Evaluation and Recommendation of Pharmacopoeial Texts for Use in
the
ICH Regions on Test for Extractable Volume of Parenteral Preparations
General Chapter
Q4B ANNEX 3 Evaluation and Recommendation of Pharmacopoeial Texts for Use in
the
ICH Regions on Test for Particulate Contamination: Sub-Visible Particles
General Chapter
Q4B ANNEX
4A
Evaluation and Recommendation of Pharmacopoeial Texts for Use in the
ICH Regions on MICROBIOLOGICAL EXAMINATION of Non-Sterile
ProdMicrobial Enumerations Tests General Chapter
Q4B ANNEX
4B
Evaluation and Recommendation of Pharmacopoeial Texts for Use in the
ICH Regions on Microbiological Examination of Non-Sterile Products:
Test for Specified Micro-Organisms General Chapter
1.4 Control of organic impurities:
Control of the organic impurities in new drug substances is based on the maximum
daily
Q4B ANNEX
4C
Evaluation and Recommendation of Pharmacopoeial Texts for Use in the
ICH Regions on Microbiological Examination of Non-Sterile Products:
Acceptance Criteria for Pharmaceutical Preparations and Substances for
Pharmaceutical Use General Chapter
Q4B ANNEX 6
Evaluation and Recommendation of Pharmacopoeial Texts for Use in the
ICH Regions on Uniformity of Dosage Units General Chapter
Q4B ANNEX 7
Evaluation and Recommendation of Pharmacopoeial Texts for Use in the
ICH Region on Dissolution Test General Chapter
Q4B ANNEX 8
Evaluation and Recommendation of Pharmacopoeial Texts for Use in the
ICH Regions on Sterility Test General Chapter
Q4B ANNEX 9
Evaluation and Recommendation of Pharmacopoeial Texts for Use in the
ICH Regions on Tablet Friability General Chapter
Q4B ANNEX
10
Evaluation and Recommendation of Pharmacopoeial Texts for Use in the
ICH Regions on Polyacrylamide Gel Electrophoresis General Chapter
Q5A(R1)
Viral Safety Evaluation of Biotechnology Products Derived From Cell
Lines of Human or Animal Origin
Q5B
Quality of Biotechnological Products: Analysis of the Expression
Construct in Cells Used for Production of R-DNA Derived Protein
Products
Q5C
Quality of Biotechnological Products: Stability Testing of
Biotechnological/ Biological Products
Q5D
Derivation and Characterisation of Cell Substrates Used for Production of
Biotechnological/Biological Products
Q5E
Comparability of Biotechnological/Biological Products Subject to Changes
in Their Manufacturing Process
Q6A
Specifications: Test Procedures and Acceptance Criteria for New Drug
Substances and New Drug Products: Chemical Substances
Q6B Specifications: Test Procedures and Acceptance Criteria for
Biotechnological/Biological Products
Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
Q8(R2) Pharmaceutical Development
Q9 Quality Risk Management
Q10 Pharmaceutical Quality system
