Modifica secondaria di un'autorizzazione all'immissione in  commercio
di specialita' medicinale per uso umano. Modifica apportata ai  sensi
          del Decreto Legislativo 29 dicembre 2007, n. 274. 
 

  Specialita' medicinale:BRIMOFTAL. Confezioni e numeri AIC: "2 mg/ml
collirio, soluzione" 1 flacone da 5 ml - AIC n. 038714010/M; "2 mg/ml
collirio, soluzione" 3 flaconi da 5 ml - AIC n. 038714022/M; "2 mg/ml
collirio, soluzione" 6 flaconi da 5 ml - AIC n. 038714034/M; "2 mg/ml
collirio, soluzione" 1 flacone da 10 ml  -  AIC  n.  038714046/M;  "2
mg/ml collirio, soluzione" 3 flaconi da 10 ml - AIC n. 038714059/M. 
  Modifiche  apportate  ai  sensi  del  Regolamento  (CE)  1234/2008:
Grouping of Variation Tipo IB e IA 
  MPR DK/H/1384/001/IB/007/G - Codice Pratica C1B/2011/2081 
  Variazione  Tipo  IB  n.B.I.a.2.e:  Changes  in  the  manufacturing
process of the active substance. Minor change to the restricted  part
of an Active Substance Master File (lowering of quantity of  solvents
and water). 
  Variazione Tipo IB n. B.I.a.3.a: Change in  batch  size  of  active
substance or intermediate up to  10-fold  increase  compared  to  the
currently approved batch size Increase in batch size to 23 kg 
  N. 8 Variazioni Tipo IA n. B.I.b.1.c: Change in  the  specification
parameters  and/or  limits   of   an   active   substance,   starting
material/intermediate/reagent used in the  manufacturing  process  of
the active substance: Addition of a new  specification  parameter  to
the specification with its corresponding  test  method:  addition  of
identification test for the starting material tartaric acid; addition
of calcium test for the starting material tartaric acid; 
  addition of chlorides test for the starting material tartaric acid;
addition  of  identification   test   for   the   starting   material
ethylendiamine; addition of purity test  for  the  starting  material
ethylendiamine; addition of  identification  test  for  the  starting
material xylene; addition of assay test  for  the  starting  material
xylene; Inclusion of identification test for tartrate in  the  active
substance. 
  MPR DK/H/1384/001/IB/008/G - Codice Pratica C1B/2011/2082 
  Variazione Tipo IA n.B.I.a.3.a: Change  in  batch  size  of  active
substance or intermediate up to  10-fold  increase  compared  to  the
currently approved batch size. 
  Variazione Tipo IA n.B.I.c.1.a: Change in  immediate  packaging  of
the active substance. Qualitative and/or quantitative composition. 
  Variazione Tipo IB n.B.I.b.z:  Change  in  control  of  the  active
substance. 
  Addition of impurity test. 
  MPR DK/H/1384/001/IB/009/G - Codice Pratica C1B/2011/2080 
  Variazione Tipo IA n. B.I.a.3.a: Change in  batch  size  of  active
substance or intermediate up to  10-fold  increase  compared  to  the
currently approved batch size. 
  Variazione  Tipo  IA  n.B.I.b.1.c:  Change  in  the   specification
parameters  and/or  limits   of   an   active   substance,   starting
material/intermediate/reagent used in the  manufacturing  process  of
the active substance Addition of a new specification parameter to the
specification with its corresponding test method:  Identification  of
tartrate. 
  Variazione Tipo IB n. B.I.b.z: Change  in  control  of  the  active
substance. 
  Inclusion of additional documentation for impurities. 
  Variazione Tipo IB n.B.I.b.2.e: Change in test procedure for active
substance  or  starting  material/reagent/intermediate  used  in  the
manufacturing process of the active substance.  Other  changes  to  a
test procedure (including replacement  or  addition)  or  the  active
substance or a starting material/intermediate - Method validation for
assay. 
  Variazione Tipo IB n.B.I.b.2.e: Change in test procedure for active
substance  or  starting  material/reagent/intermediate  used  in  the
manufacturing process of the active substance.  Other  changes  to  a
test procedure (including replacement  or  addition)  or  the  active
substance or a starting material/intermediate - Method validation for
related substances. 
  Variazione Tipo IB n.B.I.b.2.e: Change in test procedure for active
substance  or  starting  material/reagent/intermediate  used  in  the
manufacturing process of the active substance.  Other  changes  to  a
test procedure (including replacement  or  addition)  or  the  active
substance or a starting material/intermediate - Method validation for
residual solvents. 
  Variazione Tipo IB n.B.I.d.1.a)4. Change in re-test  period/storage
period or storage conditions of the active  substance  where  no  Ph.
Eur. Certificate of Suitability covering the retest period is part of
the approved dossier. 
  Re-test period/storage  period.  Extension  or  introduction  of  a
re-test period/storage period supported by real time data. -Extention
re-test period from 36 to 60 months. 
  MPR DK/H/1384/001/IB/010/G - Codice Pratica C1B/2011/2079 
  Variazione Tipo IB  n.  B.II.b.3.z:  Change  in  the  manufacturing
process of the finished product. Minor change  in  the  manufacturing
process of eye drops, solution  -  Change  in  amount  of  poly(vinyl
alcohol) solution. 
  Variazione Tipo IB  n.  B.II.b.3.z:  Change  in  the  manufacturing
process of the finished product. Minor change  in  the  manufacturing
process of eye drops, solution - Change in amount  of  bulk  solution
used  for  filter  saturation  MPR  DK/H/1384/001/IA/011/G  -  Codice
Pratica C1A/2011/1916 
  Variazione Tipo IA n.B.II.d.2.a: Change in test procedure  for  the
finished product. Minor changes  to  an  approved  test  procedure  -
change in preparation of test/reference solution for determination of
assay and related substances 
  Variazione Tipo IA n.B.II.d.2.a: Change in test procedure  for  the
finished product. Minor changes to an approved test procedure -  test
solution for determination of  Benzalkonium  chloride  assay  is  now
filtrated 
  Variazione Tipo IA n.: B.II.d.2.a: Change in test procedure for the
finished product. Minor changes to an approved test procedure- Change
in reference 
  Dodecyl Bromide to Dodecyl Chloride(Benzyldimethyl dodecyl ammonium
chloride) 
  MPR DK/H/1384/001/IB/012/G - Codice Pratica C1B/2011/2078 
  Variazione Tipo IB n  B.II.b.1.f:  Replacement  or  addition  of  a
manufacturing site for part or all of the  manufacturing  process  of
the finished product. 
  Site where any manufacturing operation(s) take place, except  batch
release,  batch  control,  and  secondary  packaging,   for   sterile
medicinal products manufactured using  an  aseptic  method  excluding
biological/ immunological medicinal product. 
  Variazione Tipo IB n  B.II.b.1.b:  Replacement  or  addition  of  a
manufacturing site for part or all of the  manufacturing  process  of
the finished product. 
  Primary packaging site. 
  Variazione Tipo IAin n. B.II.b.1.a: Replacement or  addition  of  a
manufacturing site for part or all of the  manufacturing  process  of
the finished product. Secondary packaging site. 
  Variazione  Tipo  IAin:  B.II.b.2.2:  Change   to   batch   release
arrangements  and  quality  control  testing  of   finished   product
including batch control/testing. 
  Variazione  Tipo  IB  n.  B.II.b.4.a:  Change  in  the  batch  size
(including batch size ranges) of the finished product up  to  10-fold
compared to the currently approved batch size. 
  I lotti gia' prodotti sono mantenuti in commercio fino alla data di
scadenza indicata in etichetta. 
  Decorrenza delle modifiche: dal giorno successivo alla  data  della
loro pubblicazione in Gazzetta Ufficiale. 

                       Il procuratore speciale 
                     dott. Maurizio De Clementi 

 
T12ADD8396