How to use the general monograph Substances for … - EDQM pdf/Stefan Almaling - General... · How...
Transcript of 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)
S. Almeling, 28/01/10 ©2010 EDQM, Council of Europe, All rights reserved
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
S. Almeling, 28/01/10 ©2010 EDQM, Council of Europe, All rights reserved
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 %
S. Almeling, 28/01/10 ©2010 EDQM, Council of Europe, All rights reserved
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
S. Almeling, 28/01/10 ©2010 EDQM, Council of Europe, All rights reserved
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!
S. Almeling, 28/01/10 ©2010 EDQM, Council of Europe, All rights reserved
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
S. Almeling, 28/01/10 ©2010 EDQM, Council of Europe, All rights reserved
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%
S. Almeling, 28/01/10 ©2010 EDQM, Council of Europe, All rights reserved
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;
• Other detectable impurities F, G
S. Almeling, 28/01/10 ©2010 EDQM, Council of Europe, All rights reserved
• Monograph has:
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
S. Almeling, 28/01/10 ©2010 EDQM, Council of Europe, All rights reserved
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
S. Almeling, 28/01/10 ©2010 EDQM, Council of Europe, All rights reserved
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;
• Other detectable impurities F, G
Substance is a semi-synthetic product derived from a fermentation product:
S. Almeling, 28/01/10 ©2010 EDQM, Council of Europe, All rights reserved
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%)
S. Almeling, 28/01/10 ©2010 EDQM, Council of Europe, All rights reserved
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.
S. Almeling, 28/01/10 ©2010 EDQM, Council of Europe, All rights reserved