Liraglutide precursor

Flammability

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

flammable solids

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Test procedure:

burning rate test: preliminary screening test

Remarks on result:

substance does not ignite and propagate combustion either by burning with flame or smouldering along 200 mm of the powder train within the 2 minutes test period

Interpretation of results:

not classified based on GHS criteria

Conclusions:

Data on the Liraglutide precursor was not available. Therefore the result is based on read across to S3 and S4.
Determination of the flammability of X14DesB30 and MI3 (dried) was performed in accordance to EC Directive 92/69/EEC Methods A10. X14DesB30 and MI3 did not ignite within 2 minutes, X14DesB30(S3) and MI3(S2) are therefore not classified as highly flammable.
Consequently, the same conclusion for the target substance (Liraglutide precursor) applies justified by the read-across hypothesis

Executive summary:

Data on the Liraglutide precursor was not available. Therefore the result is based on read across to S3 and S4.

Determination of the flammability of X14DesB30 and MI3 (dried) was performed in accordance to EC Directive 92/69/EEC Methods A10. X14DesB30 and MI3 did not ignite within 2 minutes, X14DesB30(S3) and MI3(S2) are therefore not classified as highly flammable.

Consequently, the same conclusion for the target substance (Liraglutide precursor) applies justified by the read-across hypothesis

Reference 2

Endpoint:

flammable solids

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003.06.30 - 2003.07.14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method A.10 (Flammability (Solids))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL (MI3)
- Appearance: cream powder
- Source and lot/batch No.of test material: QC202426
- Expiration date of the lot/batch: June 2004
- Purity test date: 2003-06-18
- Purity: 84% w/w (stated ny Sponsor)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Frozen below - 10°C

Key result

Test procedure:

burning rate test: preliminary screening test

Remarks:

A full preliminary test (train test) was performed

Burning time:

ca. 2 min

Moisture (wt %):

8.28

Remarks on result:

substance does not ignite and propagate combustion either by burning with flame or smouldering along 200 mm of the powder train within the 2 minutes test period

Interpretation of results:

not classified based on GHS criteria

Conclusions:

Determination of the flammability of MI3 (dried) was performed in accordance to EC Directive 92/69/EEC Methods A10. MI3 did not ignite within 2 minutes and is therefore not classified as highly flammable.

Executive summary:

Determination of the flammability of MI3 (dried) was performed in accordance to EC Directive 92/69/EEC Methods A10. MI3 did not ignite within 2 minutes, small amounts of orange sparks was observed when the flame was applied to the pile of MI3, which blackened and expanded to approximately double its original size. Therefore, MI3 is not classified as highly flammable. In addition the average moisture content was measured to 8.28 %^W/_W.  

Reference 3

Endpoint:

flammable solids

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003.05.12 -2003.10.24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method A.10 (Flammability (Solids))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL (X14desB30, dried)
- Appearance: cream powder
- Source and lot/batch No.of test material: QX14203119
- Expiration date of the lot/batch: June 2004
- Purity test date: 2003-06-18
- Purity: 75% w/w
 
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Frozen below - 10°C

Key result

Test procedure:

burning rate test: preliminary screening test

Moisture (wt %):

6.36

Remarks on result:

substance does not ignite and propagate combustion either by burning with flame or smouldering along 200 mm of the powder train within the 2 minutes test period

Conclusions:

Determination of the flammability of X14desB30 (dried) was performed in accordance to EC Directive 92/69/EEC Methods A10. X14desB30 was not found to be classified as highly flammable.

Executive summary:

Determination of the flammability of X14desB30 (dried) was performed in accordance to EC Directive 92/69/EEC Methods A10. The average moisture content was measured to 8.28 %W/W. X14desB30 did not ignite within 2 minutes (cone and train test), small amounts of orange sparks was observed when the flame was applied to X14desB30, which slightly expanded black solid. Therefore, X14desB30 is not classified as highly flammable.

Description of key information

Data on target substance not available. Thus, read-across has been applied using data from source substances (S3 and S4).

The target substance liraglutide precursor is a single-chain polypeptide consisting of 31 amino acids having an almost identical amino acid sequence as the human glucagon-like peptide 1 (GLP-1) that has 30 amino acids of which 29 amino acids in common with the target substance.

The target substance is a part of the active pharmaceutical ingredient: liraglutide (S1) as the liraglutide molecule has been obtained from the liraglutide precusor be the addition of a plamitoyl-ϒ-glutamate unit attached to the amino acid lysine in position 26 of the precusor.

S3 and S4 substances are somewhat larger polypeptides as consisting of 53 and 50 amino acids in the polypeptide chain.

 

Each of the amino acids in the above mentioned substances are and very polar molecules and when linked together in polypeptides the very polar nature of the polypeptides are considered as having very similar physicochemical properties irrespective whether they contain 31 (T) or 50 amino acids (S3,S4) for which physicochemical properties have been obtained. Thus, the results from physicochemical guideline testing for S3 and S4 for melting point, boiling point, flammability, self-ignition, and explosionwere identical and can be considered as representative for the target substance as well. With respect to vapour pressure the vapour pressure for single amino acids is extremely low (below 0.4 Pa) and thus, the vapour pressure for polypeptides would be expected to be even lower.

Data matrix for S1, S2, S3 and T is provided in section 13.

Key value for chemical safety assessment

Flammability:

not classified

Justification for classification or non-classification

Determination of the flammability of X14DesB30 and MI3 (dried) was performed in accordance to EC Directive 92/69/EEC Methods A10. X14DesB30 and MI3 did not ignite within 2 minutes, X14DesB30(S3) and MI3(S2) are therefore not classified as highly flammable.

Consequently, the same conclusion for the target substance (Liraglutide precursor) applies, justified by the read-across hypothesis