The Variation Regulations (EC) 541/95 1 and (EC) 542/95 2
being revised by the European Commission.
Proposals for changes to these regulations have been prepared by the
Notice to Applicants Group and were released to the industry for comments
at the beginning of February this year. The planned date for the
finalisation of the proposal is 1 August 2002.
The proposal for a revision of the Variations Regulations lists four
different categories of variations as summarised below:
(1) Type I Variation (Notification Variation)
Type I Variations have been redefined as 'minor' changes which only
have to be notified to the competent authorities and therefore are called
the 'Tell, wait, then do'-procedure. This procedure often
referred to as Type 0 is intended to provide for rapid processing of
variations (time frame 0 to 14 days).
A total of 52 Type I Variations are listed in Annex I to the proposal
for the revision of regulations 541/95 and 542/95 (draft 6). In the
current list there are 34 Type I Variations.
(2) Type II A (the current Type I Variation)
The Type IIA Variations are the 'minor' changes that implicit approval
within a 30-day waiting period.
42 variations are listed in Annex II to the proposal for the revision
of regulations 541/95 and 542/95 (draft 6). The asterisked Type I
Variations among the current Type I Variations (Type I changes for which
Type II procedures apply to products covered by Immunological/Veterinary
Immunological Products, Blood Products, High Tech Products concerning
87/22/EEC, products concerning Regulation EC 2309/93) are expected to
become a Type IIA Variation.
(3) Type IIB (the current Type II Variation)
The Type IIB Variations are the 'major' changes that explicit approval.
An approval has to be waited for (time frame: 60 days with an option to
extend to 90 days). All changes that are not Type I, Type IIA or
Extensions, are categorised as Type IIB.
What is new is the fourth category for line extensions that have been
legally defined for the first time in the EU. 'Extension' applies to
products with the same legal name, but where defined changes have been
made, e.g. replacement of the active substance(s) by a different
salt/ester complex or derivative, where the efficacy/safety remains the
same, changes to strength, pharmaceutical form and route of
For these variations, e.g. the introduction of a new pharmaceutical
form under the Mutual Recognition Procedure, the MA-holder (marketing
authorisation holder) would have to inform the original Reference Member
State about this variation.
All in all, it will be interesting what comments industry will make on
the proposal for the revision of the Variation Regulation and how the
European Commission will react to them. Let us look forward to August this
The new Variation Regulation will be among the topics of the Regulatory
Affairs Part of the 5th CEFIC/APIC European Conference on
Active Pharmaceutical Ingredients that takes place from 13 to 15 November
2002 in Barcelona/Spain. Please click here
Dr Barbara Jentges