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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
1,2-Dichloroethane (EDC)
EC Number
203-458-1
CAS Number
107-06-2
Entry Nr in Annex XIV
26
Use name
The use of 1,2 dichloroethane (1,2-DCE) as a solvent in the manufacturing of the active pharmaceutical ingredient prednisolone steaglate.
Broad information on use applied for (conditions of use and function)
1,2-Dichloroethane (1,2-DCE) is used as a solvent in the manufacture of Prednisolone steaglate, an active pharmaceutical ingredient (API) used for the production of a corticosteroid medicinal product for the treatment of inflammation (skin, joints, lungs and other organs), severe asthma, allergies and arthritis. It is most commonly used within paediatrics, i.e. to treat children, and it is only marketed in Venezuela. Prednisolone steaglate is a pro-drug of prednisolone, i.e. it can be metabolized in the body to produce the free steroid.

The manufacture of Prednisolone steaglate is a batch-wise process consisting of several steps. 1,2-DCE is used as a solvent for the manufacture of one of the intermediates during this multi-step process. To this end, all reactants and 1,2-DCE are added to a closed reactor. The desired intermediate is formed in the reactor. When the reaction is terminated, 1,2-DCE and the remaining reactants are evaporated from the reactor. The desired Prednisolone steaglate intermediate is collected from the reactor and used in the next reaction step.

The installations used for the production of Prednisolone steaglate are characterized by a high level of containment, which is inherent to the manufacture of active pharmaceutical ingredients. The reactor is closed and all transfer of (mixtures containing) 1,2-DCE occurs via fixed piping.

Additional information on the manufacture process, including OCs & RMMs per activity, is given in the exposure scenario in the CSR.

Function of 1,2-DCE: 1,2-DCE is used as a solvent for the manufacture of an intermediate in the synthesis of Prednisolone steaglate:

  • drives the reaction to completion ensuring a sufficient purity profile of the intermediate
  • allows the complete elimination (<1000 ppm) of unreacted residues of an unwanted reactant (substance claimed confidential), after completion of reaction
Requirements in case of a direct substitute for 1,2-DCE:

  • Have a high purity to ensure high purity of the end product (pharmaceutical quality)
  • Lead to the manufacture of products with identical molecular structures as the current API
  • Have a specific solubility towards the reactants (soluble) and to the desired intermediate (insoluble, in order to facilitate the elimination of the solvent from the intermediate after the reaction’s completion)
  • Have a specific boiling point: higher than the reactant that needs to be evaporated, but below the temperature at which the desired intermediate dissociates (>80oC, <120oC))
  • Low auto-ignition temperature and lower explosion limits to avoid explosion hazard
  • Have a good chemical compatibility with the reactants and the intermediate, to avoid by-products
Market (customers): Pharmaceutics (patients)

Note: The pharmaceutical market is highly regulated. Any change in the production of the API (e.g. change of solvent, production location, or change in process) would require both a requalification of the API as well as reapplying for market approval for the resulting medicinal product made. Both processes would take a long time and would be expensive.

Annual tonnage used: 0.180 tonnes/ year
Review period requested: 20 years
Use applied for number in application for authorisation
2
Broad information on use applied for (Use descriptor system)
Sector of end use (SU): 9
Environmental release category (ERC): 4
Process category (PROC): 1, 3, 8b
Product category (PC): 29
Article category related to subsequent service life (AC): Not applicable
Technical Function: Solvents
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
0111-02
Applicant(s)
OLON Spa
Application type
Initial
Status
Commission decided
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)
Link
Authorisation decision
C(2019)1577

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