how to use the general monograph substances for … - edqm pdf/stefan almaling - general... · how...

How to use the general monograph “Substances for Pharmaceutical Use”How to use the general monograph How to use the general monograph

““Substances for Pharmaceutical UseSubstances for Pharmaceutical Use””

Stefan AlmelingDeputy Head of Laboratory Department

S. Almeling, 28/01/10 ©2010 EDQM, Council of Europe, All rights reserved

Substances for Pharmaceutical Use

Substances for Pharmaceutical Substances for Pharmaceutical UseUse

Related substances.Organic impurities in active substances are to be reported, identified wherever possible, and qualified

as indicated in Table 2034.-1 or in table 2034.-2 (for peptides obtained by chemical synthesis)


Requirements for active substances except synthetic peptides

Requirements for active substances Requirements for active substances except synthetic peptidesexcept synthetic peptides

Use Maximum daily dose

Reporting threshold

Identification threshold

Qualificationthreshold

Human or human and veterinary

≤ 2 g /day >0.05 per cent >0.10 per cent or daily intake >1.0 mg (whichever lower)

>0.15 per cent or daily intake >1.0 mg (whichever lower)

Human or human and veterinary

> 2 g/day >0.03 per cent >0.05 per cent > 0.05 percent

Veterinary only Not applicable >0.1 per cent 0.2 per cent >0.5 per cent


Requirements for peptides obtained by chemical synthesis (as of

supplement 6.5)

Requirements for peptides obtained Requirements for peptides obtained by chemical synthesis (as of by chemical synthesis (as of

supplement 6.5)supplement 6.5)

Reporting threshold

Identification threshold

Qualification threshold

> 0.1 % > 0.5 % > 1.0 %


Requirements do not apply forRequirements do not apply forBiological and biotechnological productsPeptides (not obtained by chem. synth.)OligonucleotidesRadiopharmaceuticalsProducts of fermentation and semi-synthetic products derived therefromHerbal drugs or herbal drug preparations


General chapter 5.10General chapter 5.10

• Defines:Basis for monographs and impurities control

Terminology

Interpretation of related substances tests

Other aspects of impurities control

• ESSENTIAL READING!


Example no.1Example no.1Substance is an active ingredient for human use with maximum daily dose ≤ 2 g: identification threshold > 0.10%; qualification threshold >0.15%

• Monograph has:• Impurity A ≤ … (2 per cent)

• Impurity D ≤ … (1 per cent)

• Any other impurity ≤ … (0.5 per cent)• Impurities section:

• Specified impurities A, B, C, D, E;

• Other detectable impurities F, G


EXAMPLE 1

Example no. 1 (continued)Example no. 1 (continued)• Impurities A and D are specified impurities with their own

acceptance criteria (2%, 1%)

• “Any other impurity” refers to B, C and E as specified impurities (limit is above identification threshold) (0.5%)

• Apply Substances for Pharmaceutical Use for all other impurities (including F, G) (0.10%)*

*Substance is an active ingredient for human use with maximum daily dose ≤ 2 g: identification threshold > 0.10%; qualification threshold >0.15%


Example no. 2Example no. 2• Monograph has:

• Impurity A ≤ … (1 per cent)

• Any other impurity ≤ … (0.10 per cent)• Impurities section:

• Specified impurities A, B, C, D, E;



• Monograph has:

EXAMPLE 2

Example no. 2 (continued)Example no. 2 (continued)Any other impurity refers to B, C, D, E, F, G and any

others (0.10%)

=> 0.2 % of impurity G or of any other impurity not in the list must be qualified

but also=> Specific thresholds to be applied to unusually

potent or toxic impurities S. Almeling, 28/01/10 ©2010 EDQM, Council of Europe, All rights reserved

Example no. 3Example no. 3

• Monograph has a TLC test:• No spot more intense … (0.5 per cent)• No impurities section


EXAMPLE 3

Example no. 3 (continued)Example no. 3 (continued)

Apply Substances for Pharmaceutical Use

• Monograph ( => 0.5%) but monograph 2034 (=> 0.10%)

Monograph needs to be revised


Example no. 4Example no. 4Monograph:

• Impurity A ≤ … (2 per cent)

• Impurity D ≤ … (1 per cent)

• Any other impurity ≤ … (0.5 per cent)

Impurities section: • Specified impurities A, B, C, D, E;


Substance is a semi-synthetic product derived from a fermentation product:


EXAMPLE 4

Example no. 4 (continued)Example no. 4 (continued)

Impurities A and D are specified impurities

“Any other impurity” refers to B, C and E as specified impurities and to all other impurities (including F, G) (0.5%)


Impurities Summary: Strategy for compliance

Impurities Summary: Strategy for compliance

Use state-of the-art methods for impurity control

Know your product and its impurity profile

Know your suppliers

Request certificate of suitability to ensure smooth approval procedure

Maintain liaison with Ph.Eur.


Thank you for your attention !Thank you for your attention !


how to use the general monograph substances for … - edqm pdf/stefan almaling - general... · how...

Documents