The  Secretary  of  the  21st  Expert  Committee  on  the  Selection  and  Use  of  Essential  Medicines    Department  of  Essential  Medicines  and  Health  Products    World  Health  Organization    20  Avenue  Appia    CH-­‐1211  Geneva  27  Switzerland    

26  January  2017    

Re:  Statement  of  support  for  addition  of  fixed-­‐dose  combinations  for  tuberculosis  to  the  World  Health  Organization  Model  List  of  Essential  Medicines  for  Children  

 Dear  Expert  Committee,    We  are  writing  to  express  our  support  for  the  addition  to  the  World  Health  Organization  (WHO)  Model  List  of  Essential  Medicines  for  Children  (EMLc)  of  two  formulations  critical  to  improving  therapy  for  children  with  drug-­‐sensitive  tuberculosis  (DS-­‐TB):  pediatric  fixed-­‐dose  combinations  (FDCs)  of  isoniazid,  rifampin,  and  pyrazinamide  (HRZ)  and  isoniazid  and  rifampin  (HR).      Access  to  appropriately  dosed,  water-­‐dispersible  FDCs  simplifies  treatment  for  children  with  TB  and  the  providers  who  care  for  them.  In  2010,  the  WHO  recommended  increased  doses  for  first-­‐line  TB  drugs  in  children,  changing  the  required  drug  ratios  for  HRZ  from  60/30/150  mg  to  75/50/150  mg,  and  for  HR  from  60/30  mg  to  75/50  mg.  This  important  change  unfortunately  was  not  reflected  in  updated  formulations,  necessitating  provider  improvisation  to  achieve  appropriate  doses  using  single  tablets  and  inappropriately  dosed  FDCs.  In  2015,  Macleods  was  the  first  manufacturer  to  introduce  new  pediatric  FDCs  of  HRZ  and  HR  with  drug  ratios  aligned  with  the  increased  doses  recommended  by  the  WHO.1  Other  companies,  including  Lupin,  Sanofi,  Sandoz,  and  Svizera,  are  at  various  stages  of  developing  and  introducing  their  own  versions.2      When  given  for  three  to  four  months,  the  new  pediatric  FDC  of  HR,  developed  for  use  during  the  continuation  phase  of  treatment  for  active  TB  disease,  can  also  be  used  for  prevention.3  This  broadens  the  potential  impact  the  pediatric  FDCs  beyond  the  one  million  children  estimated  to  develop  active  TB  each  year,  to  the  67  million  more  estimated  to  be  infected  and  at  risk  of  developing  active  TB.4    The  anti-­‐tuberculosis  medicines  section  of  the  5th  edition  of  the  WHO  EMLc  includes  language  endorsing  the  use  of  fixed-­‐dose  combinations,  but  does  not  include  information  specific  to  the  type  of  formulation  or  drugs  and  dosages  contained  therein.  Given  that  appropriately  dosed  pediatric  FDCs  are  now  available,  including  for  purchase  through  the  Global  Drug  Facility  (GDF),  we  encourage  the  Committee  to  include  these  important  details  in  the  6th  edition  of  the  WHO  EMLc.  

 

 

 Despite  availability  since  December  2015,  just  33  countries  have  placed  orders  for  the  new  pediatric  FDCs  through  the  GDF.5  The  addition  of  the  new  pediatric  FDCs  to  the  EMLc  is  critical  to  improving  uptake  and  promoting  equitable  access  for  children  to  benefit  from  the  treatment  simplifying  capabilities  of  these  formulations.  We  ask  the  Committee  to  help  pave  the  way  for  these  formulations  to  become  available  to  the  children  who  desperately  need  them  by  approving  the  WHO’s  application  to  add  pediatric  FDCs  of  HRZ  and  HR  to  the  EMLc.    We  welcome  the  opportunity  to  discuss  this  issue  further  and  ask  you  to  please  contact  lindsay.mckenna@treatmentactiongroup.org  with  any  questions.      Sincerely,    The  Community  Research  Advisors  Group  (CRAG)  Treatment  Action  Group  (TAG)  The  Global  TB  Community  Advisory  Board  (TB  CAB)                                                                                                                          1  World  Health  Organization.  Guidance  for  national  tuberculosis  programs  on  the  management  of  tuberculosis  in  children,  2nd  ed.  Geneva:  World  Health  Organization;  2014.  Available  from:  http://www.who.int/tb/publications/childtb_guidelines/en/.    2  McKenna  L.  The  pediatric  tuberculosis  treatment  pipeline:  beyond  pharmacokinetics  and  safety  data.    In:  Clayden  P,  Collins  S,  Frick  M,  et  al.;  i-­‐Base/Treatment  Action  Group.  2016  Pipeline  Report.  New  York:  Treatment  Action  Group;  15  July  2016;  p.  181–195.  Available  from:  http://www.pipelinereport.org/2016/tb-­‐pediatric-­‐treatment.    3  World  Health  Organization.  Guidelines  on  the  management  of  latent  tuberculosis  infection.  Geneva,  Switzerland:  World  Health  Organization,  2015.  Available  from:  http://www.who.int/tb/publications/ltbi_document_page/en/.   4  Dodd  PJ,  Sismanidis  C,  Seddon  JA.  Global  burden  of  drug-­‐resistant  tuberculosis  in  children:  a  mathematical  modelling  study.  Lancet  Infect  Dis,  2016.  Published  online  June  21,  2016.  http://dx.doi.org/10.1016/S1473-­‐3099(16)30132-­‐3.    5  Waning  B.  Global  Drug  Facility  Update  on  New  Pedi  TB  FDC  Procurement.  Presented  at:  2nd  Meeting  of  the  TB  Procurement  &  Market  Shaping  Action  Team;  2016  December  6;  Arlington,  VA.