TOPICS : 04- EUROPEAN PHARMACOPOEIA & INTERNATIONAL HARMONISATION / 01General Chapters and Monographs /

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14. Do I need to validate a method that is published in the Ph. Eur.?

The test methods given in monographs and general chapters have been validated in
accordance with accepted scientific practice and current recommendations on analytical
validation. Unless otherwise stated in the monograph or general chapter, validation of the test
methods by the analyst is not required. When implementing a pharmacopoeial method, the
user must assess whether and to what extent the suitability of the method under the actual
conditions of use needs to be demonstrated according to relevant monographs, general
chapters and quality systems, i. e. the correct method transfer is the responsibility of the user.
15. How can I find out which chromatography column or other equipment or reagent
was used during the development of a monograph?
Go to the Knowledge Database. Locate the monograph you are using and you should find
this information. If the information is not there, please let us know and we will do our best to
add it and inform you.
19. Can you provide relative retentions for Other detectable impurities cited in the
Impurities section of a monograph?
The EDQM does not provide such information, as it is not needed for the proper application
of the monograph.
23 I have observed a slight difference in retention times/retardation factors compared
with the monograph. What deviation is considered acceptable?
The retention times, relative retentions and retardation factors are normally not part of the
system suitability criteria; they are given for information only and are not mandatory.
Therefore, no deviation allowance is defined. In any case, the system suitability defined in the
monograph has to be satisfied in order to proceed with the testing.
24 What is the limit for specified/unspecified/unknown impurities?

Unless otherwise prescribed or justified and authorised, organic impurities in active

substances are to be reported, identified wherever possible, and qualified as indicated in
general monograph 2034, Substances for pharmaceutical use (Table 2034.-1 or Table 2034.2).
Generally, specified impurities have their own specific acceptance criterion in the monograph.
For other impurities, the decision tree in general chapter 5.10, Control of impurities in
substances for pharmaceutical use may be used to determine the applicable acceptance
criterion.
25 How to determine the total impurities? Which peaks can be disregarded?
In chromatographic tests, the disregard limit is defined as the nominal content at or below
which peaks/signals are not taken into account for calculating a sum of impurities. The
numerical values for the disregard limit and the reporting threshold are usually the same.
Peaks corresponding to the blank can also be disregarded, as well as other peaks that the
monograph explicitly states are to be disregarded.
In other words, if impurities (specified or unspecified) are above the disregard limit, they
should be taken into account for the calculation of the total impurities.
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26 The limit for unspecified impurities in the monograph is higher than the values
defined in general monograph 2034, Substances for pharmaceutical use (Table 2034.1) and general chapter 5.10, Control of impurities in substances for pharmaceutical
use.
Some monographs are awaiting revision. However, the requirements of the general
monograph are binding and must be implemented by the user as described in general
chapter 5.10. In some exceptional cases, the requirements of general monograph 2034 and
general chapter 5.10 do not apply, and different thresholds can be prescribed. In this case,
the following statement can be found in the related substances section: The thresholds
indicated under Related substances (Table 2034.-1) in the general monograph Substances
for Pharmaceutical use (2034) do not apply.
27 How are limits for impurities defined in monographs?

Limits are based on batch data that reflect the purity of the substance currently on the
European market and are not higher than the limits approved during the marketing
authorisation process.
28 I observe baseline separation when the monograph describes a peak-to-valley
ratio.
Even though a peak-to-valley ratio cannot be calculated in this case, the requirement is
fulfilled as the separation is even better than what the monograph prescribes.
29 I cannot achieve the system suitability or signal-to-noise criteria with the described
chromatographic method. Can I make any adjustments?
Please consult General Chapter 2.2.46, section Adjustment of chromatographic conditions
for a list of acceptable modifications. However, multiple modifications are not recommended,
and in any case, the system suitability criteria of the monograph and of chapter 2.2.46 must
be met.
30. The monograph does not specify a correction factor for a specified impurity.
If the monograph does not describe a correction factor, it is assumed that it is in the range
between 0.8 and 1.2 and therefore you do not need to apply a correction factor to this
impurity.

31. The monograph does not include chemical reference substances or relative
retentions for specified impurities.
This monograph might be part of our revision programme to introduce chemical reference
substances for peak identification and relative retentions for specified impurities as well as an
explicit acceptance criterion for unspecified impurities. Please contact us if you can submit
further information.

32. What is the difference between a peak area comparison and a quantitative limit for
related substances?

In the past, the acceptance criteria for related substances were expressed relative to the area
of a reference peak of known concentration (limit test). Without providing a numerical result,
the comparison of peak areas leads to a pass/fail decision. For comparative tests, the
approximate content of impurity tolerated, or the sum of impurities, is indicated in brackets for
information only. In most cases, current monographs describe quantitative determinations: a
calculation of the content is necessary to establish compliance with the monograph.

33. In the case of a harmonised monograph, is it possible to use a reference standard

from a different pharmacopoeia?
No. The use of a European Pharmacopoeia monograph requires the use of European
Pharmacopoeia reference standards that are reviewed and approved by the European
Pharmacopoeia Commission.

34. Is it possible to perform a type of measurement (such as ATR) different from that
described in the monograph?
In principle, you can choose one of the methods described in chapter 2.2.24, unless the
monograph prescribes a comparison with a reference spectrum or an explicit preparation.
Alternatively, cross-validation with the monograph method is required. In any case, you have
to apply the same procedures for the substance to be examined and the reference standard,
under the same conditions.

35. Do I have to perform all the tests described in the Identification section of a
monograph?
No, the test or tests that constitute the First identification may be used in all circumstances.
The second identification series is not intended for use in any other context than pharmacies.
It may be used only if it can be demonstrated that the substance or preparation is fully
traceable to a batch certified to comply with all the other requirements of the monograph.

46. When should I apply Chapter 2.9.40 UNIFORMITY OF DOSAGE UNITS?

From a pharmaceutical quality point of view, the approach taken in the harmonised general
chapter on uniformity of dosage units (2.9.40) is considered equivalent to what was required

in general chapters 2.9.5 and 2.9.6. Thus, the decision on what approach to take is left to the
user. Either 2.9.40 or 2.9.5 and 2.9.6 may be applied to demonstrate compliance with the Ph.
Eur. with regard to the uniformity of dosage units.
For more details, you can also consult the Questions & Answers provided by the Quality
Working Party of the European Medicines Agency on their website