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Adopted opinions and previous consultations on applications for authorisation

Adopted opinions and previous consultations on applications for authorisation

 

This page provides further information on the applications for authorisation or review reports, which have undergone public 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. The European Commission's decision-making process can be followed through the comitology register, where further information is published about the REACH Committee's past and upcoming meetings.

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Substance Details

Name
Bis(2-methoxyethyl) ether
EC Number
203-924-4
CAS Number
111-96-6
Entry Nr in Annex XIV
25
Use name
Use of diglyme as a solvent for the synthesis of the anti-HIV active pharmaceutical ingredient (API) dapivirine.
Broad information on use applied for (conditions of use and function)
Function of diglyme:
Diglyme is used at one industrial site as a solvent in the synthesis process of an active pharmaceutical ingredient (API) named dapivirine, which is a pyrimidine derivative. The function of diglyme is to enable the reaction forming the final synthesis precursor (TMC-2 crude) of dapivirine and isolate it as solid material. The reaction is a nucleophilic substitution reaction that makes use of the substance TMC-1 pure as precursor for the synthesis of the API.

Functional requirements:
The API is manufactured in a batch process where the purity of the API, the yield of the process and the process safety are the key elements which define the requirements for the substance. The substance has to provide proper conditions for the reaction, but also needs to support an efficient separation of the end product from the reaction mixture. The manufactured API is used by a sole customer for the production of a medicinal product (vaginal ring). Aim of the product is to reduce the risk of transmission of HIV infection in women in sub-Sahara countries in a cultural context where the use of other prevention measures is less successful. The API is slowly released from the product at the site of potential infection over the course of a month, with low systemic absorption.

Phase III clinical trials of the ring have been completed successfully, and it is now a subject of regulatory approval. In the current planning distribution of the ring is foreseen to be started in 2020-2021 and will increase by 2026 when it is expected to provide the ring to 1 million women.

As the pharmaceutical market is highly regulated, any change in the manufacture of the API (e.g. change of solvent, process, or production location) will require both a revalidation of the manufacture process and confirmation of the API quality, as well as reapplying for marketing approval for the resulting medicinal product.

Key elements on the condition of use:
The batch manufacture of the API can either happen in a pilot size installation or a commercial size installation. Both installations have a high level of containment. Conceptually the installations are similar but the commercial installation has a higher level of automation and containment. Diglyme is used in the final chemical reaction step of the API manufacture. The reaction product is purified and micronized to result in the API. The solvent is recovered after the reaction process and is disposed of. Vapours containing diglyme generated during the execution of the different process steps are absorbed in a scrubber and destroyed by a thermal oxidizer.

Annual tonnage used: 1 - 10 tonnes per year
Requested review period: 7 years
Use applied for number in application for authorisation
1
Broad information on use applied for (Use descriptor system)
Sector of end use (SU): 9
Environmental release category (ERC): 4
Process category (PROC): 3, 8b, 9, 28
Product category (PC): 29
Article category related to subsequent service life (AC): Not applicable
Technical Function: Solvent
Summary table of RMMs and OCs (non confidential)
Section 9 and 10 of the CSR (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
0125-01
Applicant(s)
N.V. Ajinomoto OmniChem S.A.
Application type
Initial
Status
Commission decided
Other consultations on the same/ similar use
Comments submitted to date
Download
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)
Link
Authorisation decision
C(2019)4123

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