Tunga metaller / Heavy metals
ICH Q3d & Farmakope
Rolf Arndt Cambrex Karlskoga
Tunga metaller / Heavy metals
Rolf Arndt
-Quality Assurance Cambrex Karlskoga
- Svenska Farmakopekommitten / Working Party HM
© 2011 Cambrex Corporation. All rights reserved.
A member of a global Group
Cambrex Karlskoga is a member of Cambrex Corporation:
• Formed in 1981
• Headquarters in New Jersey, USA
Locations:
Charles City, USA
HQ, East Rutherford, USA
Karlskoga, Sweden
Tallinn, Estonia
Wiesbaden, Germany
Milan, Italy
Hyderabad, India
Cambrex has a strong position
• Total focus on small molecule intermediates and active
pharmaceutical ingredients (APIs)
– proprietary intermediates and APIs
– custom development and manufacturing services
• Niche business
– controlled substances
– generic APIs
– high energy
– high potency
• Diversified technologies
Cambrex Karlskoga API Manufacture
• Located in Karlskoga, Sweden,
250 km west of Stockholm
• 350 employees
• Extensive lab facilities,
including kilo lab
• 10 production units, including
4 pilot plants
• Full-function company
© 2011 Cambrex Corporation. All rights reserved.
Tunga metaller / Heavy metals
Rolf Arndt
-Quality Assurance Cambrex Karlskoga
- Svenska Farmakopekommitten / Working Party HM
© 2011 Cambrex Corporation. All rights reserved.
Hur samarbetar Ph Eur och Myndigheter
Tunga metaller / Heavy metals
- En snabb historisk tillbakablick
- ICH Q3 d
- Ph Eur 5.20 och 2.4.20
- Vad händer sedan för Ph Eur
- Exempel på utvärdering enligt ICH Q3d
Tunga metaller / Heavy metals
- En snabb historisk tillbakablick
- ICH Q3 d
- Ph Eur 5.20 och 2.4.20
- Vad händer sedan för Ph Eur
- Exempel på utvärdering enligt ICH Q3d
Historisk tillbakablick / Heavy metal
- Infördes USP VIII (ungefär 100 år sedan)
- Infördes i Tyska och Schweiz Pharmacopea
- USP XII (1942) infördes Pb som standard och även Cu var av intresse
To reduce the risk of intake of toxic metals by the patient and to ensure a
high chemical quality of the pharmaceutical substance
Historisk tillbakablick / Tunga metaller
Historisk tillbakablick/ EMA Guideline
Historisk tillbakablick / EDQM
EDQM
PharmEuropa 23:2 / 2011
Ph Eur, USP & JP
Ph Eur Method A – G
USP Method I - III
Tunga metaller / Heavy metals
- En historisk tillbakablick
- ICH Q3 d
- Ph Eur 5.20 och 2.4.20
- Vad händer sedan för Ph Eur
- Exempel på utvärdering enligt ICH Q3d
ICH Q3d / Heavy metals
The proposed new Guideline Q3D will provide
clarification of the requirements for metals,
which are included in the ICH inorganic
impurities classification.
ICH Q3d/ Heavy metals
ICH Q3d/ Heavy metals
Arsenik
Kvicksilver
Bly
Kadmium
ICH Q3d/ Heavy metals
ICH Q3d/ Heavy metals
ICH Q3d/ Heavy metals
Only Control what you have to control
and nothing else!
Tunga metaller / Heavy metals
- En historisk tillbakablick
- ICH Q3 d
- Ph Eur 5.20 och 2.4.20
- Vad händer sedan för Ph Eur
- Exempel på utvärdering enligt ICH Q3d
EDQM
2.4.20. DETERMINATION OF METAL CATALYSTS OR
METAL REAGENTS RESIDUES
• General approach for the evaluation of metal catalysts or
metal reagents residues in the substances for pharmaceutical
use
• It is not possible to describe all suitable sample preparation
and measurement methods. Therefore, all methods that fulfil
the described requirements may be used.
•If no sample preparation and/or measurement method is
described in the specific monograph, a suitable sample
preparation and/or measurement method must be developed and
validated
EDQM
2.4.20. DETERMINATION OF METAL CATALYSTS OR
METAL REAGENTS RESIDUES
• A system suitability test must be performed on the day of the
analysis.
• Before the initial use of a method, the analyst must ensure that
the method is appropriate for the samples and instruments used.
This is accomplished by following a validation procedure for
methods not described in the specific monograph or by a
system suitability test for methods described in the monograph.
EDQM
2.4.20. DETERMINATION OF METAL CATALYSTS OR
METAL REAGENTS RESIDUES
•PROCEDURES
SAMPLE PREPARATION & MEASUREMENT
Preparation of sample solution. Acceptance criterion & Measurement system
Acceptance criterion:
•VALIDATION REQUIREMENTS
SPECIFICITY, LINEARITY, RANGE, ACCURACY, REPEATABILITY,
INTERMEDIATE PRECISION, LIMIT OF QUANTIFICATION, LIMIT OF
DETECTION (ONLY APPLICABLE TO LIMIT TESTS)
Including acceptance criteria
Tunga metaller / Heavy metals
- En historisk tillbakablick
- ICH Q3 d
- Ph Eur 5.20 och 2.4.20
- Vad händer sedan för Ph Eur
- Exempel på utvärdering enligt ICH Q3d
Vad händer sedan?
Vad händer sedan?
• 2.4.8 Heavy metals
• 2.4.2 Arsenic
• 2.4.10 Lead in sugar
• 2.4.15 Nickel in Polyols
•2.4.20 Determination of metal catalyst or metal reagent
residues
Vad händer sedan?
Tunga metaller / Heavy metals
- En historisk tillbakablick
- ICH Q3 d
- Ph Eur 5.20 och 2.4.20
- Vad händer sedan för Ph Eur
- Exempel på utvärdering enligt ICH Q3d
Exempel / Tunga metaller
Exempel / Tunga metaller
Exempel / Tunga metaller
Tack för mig
Och
????