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Aangenomen adviezen en eerdere raadplegingen over autorisatieaanvragen

Aangenomen adviezen en eerdere raadplegingen over autorisatieaanvragen

This page provides further information on the applications for authorisation or review reports, which have undergone consultation. The applications for authorisation are in the opinion development phase until the final opinions of the Committees for Risk Assessment and Socio-economic Analysis have been adopted and sent to the European Commission. Its decision-making process can be followed through the comitology register, where further information is published about the REACH Committee's past and upcoming meetings.

On 1 February 2020, the United Kingdom (UK) withdrew from the EU. The transition period provided by the withdrawal agreement ended on 31 December 2020. As of 1 January 2021, an application for an authorisation submitted by a person established in the UK (except Northern Ireland) is no longer valid in the EU, unless that application has been transferred to a legal entity established in the EU or Northern Ireland before the end of the transition period. Therefore, authorisation applications and decisions in so far as these concern persons established in the UK (except Northern Ireland) are no longer considered valid. 

 

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Substance Details

Name
4-(1,1,3,3-tetramethylbutyl)phenol, ethoxylated
EC Number
-
CAS Number
-
Entry Nr in Annex XIV
42
Use name
Use of 4-(1,1,3,3-tetramethylbutyl)phenol, ethoxylated as a detergent in the purification process of G-CSF (Granulocyte Colony Stimulating Factor) inclusion bodies
Broad information on use applied for (conditions of use and function)

Triton™ X-100 (a mixture of homologous molecules of the 4-(1,1,3,3-tetramethylbutyl) phenol, ethoxylated substance group) is used as detergent in a wash buffer during the purification process of G-CSF (Filgrastim) inclusion bodies. G-CSF is the precursor of PEG-Filgrastim, a biosimilar drug used to prevent the occurrence or reduce the duration of febrile neutropenia in cancer patients receiving immunosuppressive chemotherapy.

G-CSF protein is initially expressed in recombinant E. coli bacteria in the form of inclusion bodies - dense, solid intracellular protein aggregates. These inclusion bodies must be separated from culture-related impurities and from potentially immunogenic compounds (mainly by-products of the cell’s metabolism such as bacterial endotoxins, host cell proteins and residual host DNA).

An important fraction of these impurities adheres non-specifically to the “outer surface” of the inclusion bodies and have to be removed (in this case, via a Triton™ X-100-based washing procedure) in order to guarantee the quality, safety and efficacy of the final medicinal product PEG-Filgrastim. PEG-Filgrastim is obtained by chemical PEGylation of the G-CSF molecule.

Within this washing procedure, the presence of Triton™ X-100 is crucial as it has multiple technical functionalities:

  • It has unique hydrophilic and lipophilic properties enabling selective solubilization of immunogenic compounds without further solubilizing G-CSF inclusion bodies, enabling robust separation with high purity and yield;
  • It provides its selective solubilization properties under defined process conditions;
  • It is compatible with all process chemicals, with the overall technical purification process, under the defined process conditions.

All technical functionalities listed are required for the purification process of G-CSF and are of pivotal importance for the quality, safety and efficacy of the final medicinal product PEG-Filgrastim.

Annual tonnage used: < 2 tonnes/year

Review period requested: 9 years

Use applied for number in application for authorisation
1
Broad information on use applied for (Use descriptor system)
Sector of end use (SU): 0: Other: Pharmaceutical industry
Environmental release category (ERC): 4
Process category (PROC): 1, 8a, 9, 15, 28
Product category (PC): 0: Other: Detergent
Article category related to subsequent service life (AC): n/a
Technical Function: Solubilization detergent for host cell related impurities
Summary table of RMMs and OCs (non confidential)
Chemical Safety Report (original and updated, if available) (non confidential)
Analysis of Alternatives (non confidential report)
Substitution Plan (non confidential summary)
Socio-Economic Analysis (non confidential report)
Joint Analysis of Alternatives and Socio-Economic Analysis (non confidential report)
Explanatory note
Additional information
ID
0157-01
Applicant(s)
Merck Biodevelopment SAS
Fujifilm Diosynth Biotechnologies (UK) Ltd - [Application void as of 01/01/2021]
Application type
Initial
Status
Opinions adopted
Other consultations on the same/ similar use
Comments submitted to date
No comments received
Response to comments by applicant
Responses to RAC and SEAC requests by Applicant(s) (non confidential)
Compiled RAC and SEAC opinions
Minority positions
Adopted commission decision (OJ summary)
Authorisation decision

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