Liraglutide precursor

Auto flammability

Link to relevant study record(s)

Reference

Endpoint:

relative self-ignition temperature (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.16 (Relative Self-Ignition Temperature for Solids)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL (MI3 dried)
- 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 by Sponsor)

Key result

Relative self-ignition temperature:

> 400 °C

Remarks on result:

no self ignition observed under the test conditions

Remarks:

No self-ignition was observed below 400°C

Before heating, the MI3 was a cream powder. There was small exothermic event at approximately 200°C, possible related to a thermal transition or decomposition of the MI3. There was not observed any exotherm sufficient to cause auto flammabillity (self-ignition). After heating, an expanded black residue approximately double its original volume was present in the petri at the bottom of the furnace.

Conclusions:

Determination of the auto flammability (self-ignition) of MI3 (dried) was performed in accordance to EC Directive 92/69/EEC Methods A16. No relative self-ignition was observed when heating MI3 to 400 ºC, the highest temperature tested.

Executive summary:

Determination of the auto flammability (self-ignition) of MI3 (dried) was performed in accordance to EC Directive 92/69/EEC Methods A16. No relative self-ignition was observed when heating MI3 to 400 ºC, the highest temperature tested.  However, a small exothermic event was observed at 200ºC, possible releated to a thermal transition or decomposition of the MI3.

Description of key information

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

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.

Additional information

Determination of the auto flammability (self-ignition) of MI3 (S3) was performed in accordance to EC Directive 92/69/EEC Methods A16. No relative self-ignition was observed when heating MI3 to 400 ºC, the highest temperature tested thus, no potential for self-ignition.

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