Pharmacy	
  Track:	
  Impact	
  of	
  
Abuse-­‐Deterrent	
  Formula;ons	
  	
  
Presenters:	
  
Douglas	
  Throckmorton,	
...
Disclosures	
  
•  Douglas	
  Throckmorton	
  has	
  no	
  financial	
  conflicts	
  of	
  
interest	
  to	
  disclose.	
  
...
Learning	
  Objec9ves	
  
1.  State	
  the	
  purpose	
  for	
  u9lizing	
  abuse-­‐
deterrent	
  formula9ons.	
  	
  
2. ...
April	
  21	
  –	
  23,	
  2014	
  
MarrioR	
  Marque	
  Hotel	
  
Atlanta	
  Georgia	
  
Douglas C. Throckmorton MD
Deput...
5	
  
Learning	
  Objec;ves	
  
•  Understand	
  the	
  history	
  of	
  abuse-­‐deterrent	
  
opioid	
  development	
  	
  
•  ...
Agenda	
  	
  
•  FDA	
  work	
  to	
  support	
  the	
  development	
  of	
  
abuse-­‐deterrent	
  formula9ons	
  of	
  o...
Overall	
  Messages	
  
•  Important	
  work	
  has	
  been	
  done	
  to	
  encourage	
  the	
  
development	
  and	
  us...
Overall	
  Messages	
  (cont)	
  
•  Work	
  on	
  ADF	
  development	
  is	
  one	
  part	
  of	
  the	
  
FDA	
  efforts	...
“GUIDANCE	
  FOR	
  INDUSTRY	
  
	
  ABUSE	
  DETERRENT	
  OPIOIDS—EVALUATION	
  AND	
  
LABELING”	
  
10
DraU	
  Guidance	
  on	
  Abuse-­‐Deterrent	
  
(AD)	
  Formula;ons	
  of	
  Opioids	
  
•  Early	
  experience	
  with	
 ...
DraU	
  Guidance	
  on	
  AD	
  	
  
Opioid	
  Formula;ons	
  (cont)	
  
•  Follows	
  earlier	
  related	
  draY	
  Guida...
DraU	
  Guidance	
  on	
  AD	
  	
  
Opioid	
  Formula;ons	
  (cont)	
  
•  Ini9al	
  focus	
  is	
  on	
  opioids	
  
•  ...
DraU	
  Guidance	
  on	
  AD	
  Opioid	
  	
  
Formula;ons:	
  Released	
  January,	
  2013	
  
•  Purpose:	
  	
  Reflect	...
DraU	
  Guidance	
  on	
  AD	
  Opioid	
  	
  
Formula;ons	
  :	
  Highlights 	
  	
  
•  Goals:	
  Two	
  over-­‐arching	...
Highlights	
  of	
  DraU	
  Guidance	
  on	
  AD	
  
Opioid	
  Formula;ons	
  
•  Lays	
  out	
  development	
  roadmap:	
...
Labeling	
  Claims	
  for	
  Opioids	
  with	
  	
  
AD	
  Formula;ons	
  
•  Grouped	
  according	
  to	
  source	
  and	...
Addi;onal	
  Scien;fic	
  Work	
  Needed	
  	
  
•  Characterizing	
  the	
  quan9ta9ve	
  link	
  between:	
  
–  Changes	...
Unresolved	
  Issues	
  
•  Does	
  not	
  address	
  how	
  FDA	
  will	
  approach	
  generic	
  
drug	
  evalua9on,	
  ...
Since	
  Release	
  of	
  DraU	
  Guidance	
  
•  Considerable	
  industry	
  interest	
  in	
  developing	
  
AD	
  formu...
1.	
  	
  OXYCONTIN	
  AND	
  OPANA	
  ER	
  
2.	
  	
  EXTENDED-­‐RELEASE	
  AND	
  LONG-­‐ACTING	
  OPIOIDS	
  
RELABELI...
Ac;ons	
  on	
  Oxycon;n	
  &	
  Opana	
  ER	
  
•  April	
  16,	
  2013:	
  Oxycon9n	
  granted	
  labeling	
  as	
  abus...
Ac;on	
  on	
  Zohydro	
  
•  Zohydro	
  	
  
–  Member	
  of	
  Extended-­‐Release/	
  Long-­‐Ac9ng	
  (ER-­‐LA)	
  Class...
Ac;on	
  on	
  Zohydro:	
  Why	
  didn’t	
  FDA	
  
require	
  AD	
  formula;on?	
  
•  Abuse-­‐deterrent	
  technologies	...
25
Ongoing	
  Focus	
  on	
  AD	
  	
  
Formula;on	
  Development	
  
•  Con9nued	
  scien9fic	
  progress	
  
•  FDA	
  labor...
Conclusions	
  
•  Important	
  work	
  has	
  been	
  done	
  to	
  encourage	
  the	
  
development	
  and	
  use	
  of	...
Impact of Abuse-Deterrent Formulations
National Rx Drug Abuse Summit
Atlanta, Georgia
April 2014
Richard	
  C.	
  Dart,	
 ...
Disclosure	
  Statement	
  
•  "Richard	
  Dart	
  has	
  financial	
  rela9onships	
  with	
  proprietary	
  
en99es	
  th...
30
Total	
  US	
  Pharmaceu9cal	
  Opioid	
  Consump9on	
  
1980	
  –	
  2010,	
  Morphine	
  Equivalents	
  (mg	
  per	
 ...
31	
  
hRp://www.whitehouse.gov/blog/2014/02/10/5-­‐things-­‐know-­‐about-­‐opioid-­‐overdoses	
  
England and Wales Drug ...
FDA	
  DraY	
  Guidance	
  
	
  Abuse-­‐Deterrent	
  Opioids	
  -­‐	
  Evalua9on	
  and	
  Labeling	
  	
  
•  Prescrip9on...
Conflic9ng	
  Views	
  
•  …	
  FDA	
  advisory	
  commiRee	
  voted	
  against	
  approval	
  of	
  a	
  
hydrocodone	
  p...
Abuse	
  Deterrent	
  Formula9ons	
  in	
  the	
  United	
  States	
  
34
OxyContin, Opana ER, Exalgo, Oxecta, Nucynta ER
Abuse	
  Deterrent	
  Formula9ons	
  
Site	
  of	
  Ac9on	
  
35	
  
Swallow	
  
Chew	
  
Crush	
  
Snort	
  
Inject	
  
C...
RADARS	
  System	
  
Results	
  through	
  December	
  31,	
  2013	
  
36	
   36
What	
  is	
  the	
  RADARS®	
  System?	
  
•  History	
  
–  Denver	
  Public	
  Safety	
  Net	
  Hospital	
  for	
  150	...
Drug	
  
Transactions	
  
Criminal	
  Justice	
  	
  
250	
  agencies	
  	
  
49	
  states	
  
Illicit	
  Market	
  
Price...
39	
  
Principal	
  Inves;gators	
  
•  Theodore	
  J.	
  Cicero,	
  PhD	
  
	
  Washington	
  University	
  at	
  St.	
  ...
Show	
  Me	
  The	
  Data	
  
•  Do	
  ADFs	
  decrease	
  abuse?	
  
– OxyCon9n®	
  (polyethylene	
  oxide),	
  Opana	
  ...
RADARS	
  System	
  	
  
Schedule	
  II	
  Excluding	
  Oxycodone	
  ER	
  Popula9on	
  
Rates	
  by	
  Program,	
  2009-­...
42
Model	
  for	
  Oxycodone	
  Extended	
  Release	
  
RADARS	
  System	
  Poison	
  Centers	
  
0	
  
2007	
  
0.15	
  
...
ADFs–Demand	
  Reduc9on	
  
People	
  Filling	
  Prescrip9ons	
  
43
Before	
   AYer	
  ADF	
   AYer	
  ADF	
  Before	
  
...
Drug	
  Diversion	
  Program	
  
Popula9on	
  Rate,	
  2009-­‐2013	
  
44	
  *Other	
  opioids	
  excluding	
  ER	
  oxyco...
Poison	
  Center	
  Program	
  
Popula9on	
  Rate,	
  2009-­‐2013	
  
45	
  *Other	
  opioids	
  excluding	
  ER	
  oxycod...
Poison	
  Center	
  Program	
  
Route	
  of	
  Administra9on,	
  OxyCon9n	
  
Rela9on	
  of	
  Original	
  OxyCon9n	
  and	
  
Men9ons	
  in	
  Poison	
  Center	
  Program	
  
Original	
  Formula;on	
...
Case	
  Outcome	
  in	
  Poison	
  Center	
  Program	
  -­‐	
  
Major	
  Outcome	
  or	
  Death	
  
0	
  
0.005	
  
0.01	
...
Treatment	
  Programs	
  Combined	
  
2009-­‐2013	
  
49*Other	
  opioids	
  excluding	
  ER	
  oxycodone	
  and	
  ER	
  ...
StreetRx.com	
  
50
StreetRx, RADARS System Drug Diversion
and Silk Road – Price per milligram drug
51
Dasgupta, Suratt, et al, J Med Internet...
US	
  StreetRx	
  
Endorsement	
  of	
  Canadian	
  Oxycodone	
  Products	
  	
  
in	
  United	
  States	
  
52	
  
11	
  ...
Oxycodone	
  ER	
  in	
  US	
  and	
  Canada	
  
	
  Formula;on	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
 ...
Other	
  Data	
  Sources	
  
Navippro	
  Treatment	
  Centers	
  
54	
  
Butler	
  S,	
  et	
  al,	
  J	
  Pain	
  2012	
  
Other	
  Data	
  Sources	
  
Na9onal	
  Survey	
  of	
  Drug	
  Use	
  and	
  Health	
  
Good	
  News	
  –	
  Bad	
  News	...
Yes,	
  Abuse	
  Deterrent	
  Formula9ons	
  Can	
  
Reduce	
  the	
  Diversion	
  and	
  Abuse	
  of	
  an	
  Opioid	
  
...
Squeezing	
  the	
  Balloon	
  
Heroin	
  -­‐	
  Past	
  Month,	
  Past	
  Year	
  
NSDUH	
  Report	
  2012	
  
ADF	
  Oxy...
Can	
  ADFs	
  Bend	
  the	
  Curve?	
  
•  CS	
  –	
  College	
  Survey 	
  DD	
  –	
  Drug	
  Diversion	
  
•  PC	
  –	
...
Conclusions	
  
•  Formula9ons	
  that	
  resist	
  crushing	
  and	
  forming	
  
injectable	
  solu9ons	
  can	
  reduce...
Thank	
  You!	
  
60	
  
Upcoming SlideShare
Loading in …5
×

Ph 3 throckmorton dart

1,296 views

Published on

Published in: Health & Medicine
0 Comments
2 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
1,296
On SlideShare
0
From Embeds
0
Number of Embeds
9
Actions
Shares
0
Downloads
43
Comments
0
Likes
2
Embeds 0
No embeds

No notes for slide

Ph 3 throckmorton dart

  1. 1. Pharmacy  Track:  Impact  of   Abuse-­‐Deterrent  Formula;ons     Presenters:   Douglas  Throckmorton,  MD,  Deputy  Director  for  Regulatory   Programs,  Center  for  Drug  Evalua;on  and  Research,  FDA   Richard  C.  Dart,  MD,  PhD,  Director,  Rocky  Mountain  Poison  and   Drug  Center,  Professor,  University  of  Colorado   Moderator:    Peter  VanPelt,  RPh,  Associate  Director  for  Corporate   Alliances,  American  Pharmacists  Associa;on    
  2. 2. Disclosures   •  Douglas  Throckmorton  has  no  financial  conflicts  of   interest  to  disclose.   •  Richard  Dart  has  financial  rela9onships  with   proprietary  en99es  that  produce  health  care  products   and  services.  These  financial  rela9onships  are  research   funding  from  McNeil  Consumer  Healthcare  and   Bioclon.  The  RADARS  System  is  financially  supported  by   subscrip9ons  from  most  pharmaceu9cal  companies   that  produce  prescrip9on  opioids  or  s9mulants.  All   rela9onships  are  with  Denver  Health  and  Hospital   Authority,  the  public  hospital  for  Denver,  Colorado.  Dr.   Dart  receives  no  individual  compensa9on.  
  3. 3. Learning  Objec9ves   1.  State  the  purpose  for  u9lizing  abuse-­‐ deterrent  formula9ons.     2.  Analyze  emerging  trends  and  methods  for   evalua9ng  abuse-­‐deterrent  technologies.     3.  Compare  data  of  prescribers  who  use   medica9ons  with  abuse-­‐deterrent   formula9ons  versus  medica9ons  without   these  technologies  and  the  rate  of  overdoses   associated.    
  4. 4. April  21  –  23,  2014   MarrioR  Marque  Hotel   Atlanta  Georgia   Douglas C. Throckmorton MD Deputy Director for Regulatory Programs CDER, FDA
  5. 5. 5  
  6. 6. Learning  Objec;ves   •  Understand  the  history  of  abuse-­‐deterrent   opioid  development     •  Understand  the  importance  and  challenges  of   developing  and  tes9ng  successful  abuse-­‐ deterrent  opioids   •  Understand  the  importance  and  challenges  of   assessing  the  impact  of  abuse-­‐deterrent   opioids     6  
  7. 7. Agenda     •  FDA  work  to  support  the  development  of   abuse-­‐deterrent  formula9ons  of  opioids   – Abuse-­‐Deterrent  Opioids  DraY  Guidance   – Regulatory  decisions   •  Progress  in  use  of  abuse-­‐deterrent   formula9ons  of  opioids   •  Challenges  in  the  development  of  abuse-­‐ deterrent  formula9ons  of  opioids   7
  8. 8. Overall  Messages   •  Important  work  has  been  done  to  encourage  the   development  and  use  of  successful  abuse-­‐ deterrent  formula9ons  of  opioids   –  FDA  is  applying  principles  in  draY  Guidance  to   regulatory  decisions   –  DraY  Guidance  is  s9mula9ng  new  development   –  Meaningful  progress  requires  systema9c,  scien9fically   rigorous  and  flexible  approach   –  Challenges  remain  before  any  one  abuse-­‐deterrent   technology  can  be  adopted   8
  9. 9. Overall  Messages  (cont)   •  Work  on  ADF  development  is  one  part  of  the   FDA  efforts  to  confront  prescrip9on  drug  abuse   •  Improving  drugs  used  to  treat  pain   o Abuse-­‐deterrent  formula9ons  of  opioids   o New  classes  of  pain  drugs  that  lack  abuse  risk   •  Improving  safe  use  of  opioids   o Improved  educa9on  of  prescribers  and  pa9ents  to  reduce   risk  of  abuse   o Improved  surveillance  to  understand  use  of  opioids   o Improved  use  of  packaging  and  storage  of  opioids   •  Improving  treatment  of  opioid  abuse   •  Improving  treatment  of  opioid  overdose   o Naloxone  autoinjector  approval   9  
  10. 10. “GUIDANCE  FOR  INDUSTRY    ABUSE  DETERRENT  OPIOIDS—EVALUATION  AND   LABELING”   10
  11. 11. DraU  Guidance  on  Abuse-­‐Deterrent   (AD)  Formula;ons  of  Opioids   •  Early  experience  with  AD  formula9on   development     •  Focus  of  development  on  crush-­‐resistant/ extrac9on-­‐resistant  technologies  and  addi9on   of  aversive  products  (e.g.,  soaps,  naloxone)   •  No  broad  claims  for  abuse-­‐deterrence  in   labeling   •  Some  studies  included  in  labeling  (e.g.,  Oxecta)   •  No  robust  evalua9on  of  impact  of  the   formula9on  in  real  world  sedng  
  12. 12. DraU  Guidance  on  AD     Opioid  Formula;ons  (cont)   •  Follows  earlier  related  draY  Guidance:    “Assessment   of  Abuse  Poten9al  of  Drugs”,  issued  January  2010   •  hRp://www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInforma9on/Guidances/UCM198650.pdf     •  Discusses  use  of  safety  informa9on  from  all  areas  of   the  NDA,  including  brief  discussion  of  abuse-­‐ deterrent  formula9ons   12  
  13. 13. DraU  Guidance  on  AD     Opioid  Formula;ons  (cont)   •  Ini9al  focus  is  on  opioids   •  Part  of  work  to  create  safer  opioids   •  Guidance  on  AD  formula9on  development  was   promised  as  part  of  ONDCP  Rx  Drug  Abuse  Plan   (2011)   •  Guidance  on  ADF  development  mandated  under   FDASIA*     •  Goal  date  January  9,  2013   * Food and Drug Administration Safety and Innovation Act
  14. 14. DraU  Guidance  on  AD  Opioid     Formula;ons:  Released  January,  2013   •  Purpose:    Reflect  the  state  of  the  science  of   abuse  deterrence  (rela9vely  new),  and  the   need  for  flexible  approach  while  s9ll   applying  a  rigorous,  science-­‐based  standard   in  evalua9on  and  labeling  of  drugs  as  data   accumulates   14
  15. 15. DraU  Guidance  on  AD  Opioid     Formula;ons  :  Highlights     •  Goals:  Two  over-­‐arching  goals:   – Encourage  the  development  of  successful  abuse-­‐ deterrent  formula9ons  of  opioids     – Assure  appropriate  development  and  availability   of  generic  drugs,  reflec9ng  their  importance  in  US   healthcare   •  Accomplishing  Goal:       •  Encouraging  development  of  successful  abuse-­‐ deterrent  formula9ons  through  accurate   labeling   15
  16. 16. Highlights  of  DraU  Guidance  on  AD   Opioid  Formula;ons   •  Lays  out  development  roadmap:   –  Scien9fic  studies  relevant  to  assessing  impact  of   formula9on  on  abuse     –  Assessments  FDA  will  use  when  looking  at  study  data   •  Lays  out  impact  of  AD  data  on  opioid  labeling,   including  claim  for  abuse-­‐deterrence   –  Goal  to  incen9vize  meaningful  AD  formula9on   development   •  Iden9fies  areas  of  addi9onal  scien9fic  needs   16
  17. 17. Labeling  Claims  for  Opioids  with     AD  Formula;ons   •  Grouped  according  to  source  and  type  of  data   –  Tier  1:    Physical/Chemical  Barriers  to  Abuse   •  Examples:    data  on  crushing  and  extrac9on   –  Tier  2:    PK  Data   •  Clinical  serum  concentra9ons  (e.g.,  Tmax,  Cmax)   –  Tier  3:    Demonstra9on  of  Reduced  Abuse  Poten9al   •  Clinical  Abuse  Poten9al  Studies   –  Tier  4:    Demonstra9on  of  Reduced  Abuse   •  Postmarke9ng  data  on  use  and  misuse  of  marketed  product   •  Differs  according  to  technology                                                     used  to  create  formula9on   17
  18. 18. Addi;onal  Scien;fic  Work  Needed     •  Characterizing  the  quan9ta9ve  link  between:   –  Changes  in  the  pharmacokine9cs  of  opioids  in  different   formula9ons   –  Results  of  clinical  studies  using  those  same  formula9ons   –  Differences  in  abuse  in  the  community   •  Characterizing  the  best  methods  to  analyze  clinical   data  on  abuse   •  Characterizing  the  best  methods  to  analyze  the   impact  of  formula9ons  on  rates  of  abuse  in  the   community   18
  19. 19. Unresolved  Issues   •  Does  not  address  how  FDA  will  approach  generic   drug  evalua9on,  approval,  and  withdrawal   •  Does  not  set  ‘bright  line’  standard  of  what   cons9tutes  meaningful  ‘abuse  deterrence’   –  Will  need  more  experience  before  we  can  set  such  a   standard   –  Need  more  data  on  the  link  between  non-­‐clinical  and  pre-­‐ market  studies  and  post-­‐market  impact  on  abuse,   overdose,  and  death   19
  20. 20. Since  Release  of  DraU  Guidance   •  Considerable  industry  interest  in  developing   AD  formula9ons  of  opioids   •  Mul9ple  mee9ngs  with  FDA  and  manufacturers   •  Importantly,  new  approaches  to  AD  opioid   development  are  being  proposed/tested,  in   addi9on  to  crush-­‐resistant/extrac9on-­‐ resistant  technologies  
  21. 21. 1.    OXYCONTIN  AND  OPANA  ER   2.    EXTENDED-­‐RELEASE  AND  LONG-­‐ACTING  OPIOIDS   RELABELING  AND  POST-­‐MARKETING  REQUIREMENT   3.    ZOHYDRO   21
  22. 22. Ac;ons  on  Oxycon;n  &  Opana  ER   •  April  16,  2013:  Oxycon9n  granted  labeling  as  abuse-­‐ deterrent     –  The  new  labeling  indicates  that  the  product  has  physical   and  chemical  proper9es  that  are  expected  to  make  abuse   via  injec9on  difficult  and  to  reduce  abuse  via  the  intranasal   route  (snor9ng)   •  May  10,  2013:  Opana  ER  determined  not  to  have   demonstrated  abuse-­‐deterrent  proper9es   •  Decisions  based  on  scien9fic  data  from  each   applica9on  separately,  drawing  on  principles  from   draY  Guidance   22
  23. 23. Ac;on  on  Zohydro   •  Zohydro     –  Member  of  Extended-­‐Release/  Long-­‐Ac9ng  (ER-­‐LA)  Class  of  opioids   –  Similar  doses,  an9cipated  risks  of  abuse  and  an9cipated  uses  as  other   ER-­‐LA  opioids   –  Meets  statutory  requirements  for  approval   •  Iden9fiable  benefits  for  pa9ents  and  prescribers   –  Provides  addi9onal  choice  for  pa9ents  and  prescribers   –  Allows  users  of  high  doses  of  hydrocodone  to  avoid  use  of   acetaminophen  and  liver  toxicity  and  take  fewer  pills   •  Label  reflects  newly  revised  ER-­‐LA  opioid  labeling   –  Responsive  to  Advisory  CommiRee  concerns  about  ER-­‐LA  opioids   –  Increased  safety  informa9on   –  New,  focused  indica9on     –  Sponsor  is  required  to  conduct  addi9onal  studies   23
  24. 24. Ac;on  on  Zohydro:  Why  didn’t  FDA   require  AD  formula;on?   •  Abuse-­‐deterrent  technologies  are  not  a  silver   bullet  and  are  s9ll  early  stages  of  development   –  One  approved  product  that  is  abuse  deterrent   (Oxycon9n)     •  Important  first  step,  but  abuse  of  Oxycon9n  s9ll  occurs   •  Not  effec9ve  at  reducing  primary  route  of  abuse  (oral)     •  Can  be  defeated  using  easily  available  means   –  At  least  one  other  opioids  (Opana  ER)  that   incorporate  similar  technologies  designed  to  deter   abuse  failed  to  demonstrate  an  impact  on  abuse   •  This  is  not  straighsorward!   –  Premature  to  require  early  technology  when  what  is   needed  is  improved  science  and  technology  
  25. 25. 25
  26. 26. Ongoing  Focus  on  AD     Formula;on  Development   •  Con9nued  scien9fic  progress   •  FDA  laboratory  working  on  AD  formula9on  science   •  FDA  support  of  external  scien9fic  work  on  AD  formula9ons   •  Con9nued  work  to  assess  impact  of  AD  formula9ons  on   actual  abuse  and  misuse  of  opioids   •  FDA  epidemiologists  working  on  improving  tools  FDA  uses   to  assess  impact  of  AD  formula9on  of  Oxycon9n  in  US   market   •  FDA  and  USG  working  to  improve  the  surveillance  databases   used  to  assess  impact  of  AD  formula9ons  in  US  market   •  Refinement  of  our  guidance  on  the  development  of  ADFs:   •  Pathway  to  the  development  of  ADFs  of  generic  drugs   •  Refinement  of  what  is  needed  to  demonstrate  meaningful   abuse-­‐deterrence    
  27. 27. Conclusions   •  Important  work  has  been  done  to  encourage  the   development  and  use  of  successful  abuse-­‐deterrent   formula9ons  of  opioids   •  Work  to  encourage  abuse-­‐deterrent  formula9ons  of   opioids  is  one  of  many  ac9vi9es  FDA  is  doing  to   improve  the  safe  use  of  opioid  drugs   •  Improving  the  use  of  opioids  through  careful  and   appropriate  regula9ons,  including  labeling   •  Improving  the  use  of  opioid  through  educa9on       •  Improving  the  use  of  opioids  through  improved  science     •  FDA  will  con9nue  to  act  with  the  available  data  to   seek  a  balance  between  the  needs  of  pain  pa9ents   and  the  need  to  reduce  prescrip9on  drug  abuse   27
  28. 28. Impact of Abuse-Deterrent Formulations National Rx Drug Abuse Summit Atlanta, Georgia April 2014 Richard  C.  Dart,  MD,  PhD   Director,  Rocky  Mountain  Poison  and  Drug  Center   Professor,  University  of  Colorado  
  29. 29. Disclosure  Statement   •  "Richard  Dart  has  financial  rela9onships  with  proprietary   en99es  that  produce  health  care  products  and  services.”     •  These  financial  rela9onships  are  research  funding  from   McNeil  Consumer  Healthcare  and  Bioclon.     •  The  RADARS  System  is  financially  supported  by  subscrip9ons   from  most  pharmaceu9cal  companies  that  produce   prescrip9on  opioids  or  s9mulants.     •  All  rela9onships  are  with  Denver  Health  and  Hospital   Authority,  the  public  hospital  for  Denver,  Colorado.     •  Dr.  Dart  receives  no  individual  compensa9on.  
  30. 30. 30 Total  US  Pharmaceu9cal  Opioid  Consump9on   1980  –  2010,  Morphine  Equivalents  (mg  per  capita)   http://ppsg-production.heroku.com/chart 800  
  31. 31. 31   hRp://www.whitehouse.gov/blog/2014/02/10/5-­‐things-­‐know-­‐about-­‐opioid-­‐overdoses   England and Wales Drug Related Deaths 2001 - 2011 Total   Giraudon et al. Br J Clin Pharm 2013
  32. 32. FDA  DraY  Guidance    Abuse-­‐Deterrent  Opioids  -­‐  Evalua9on  and  Labeling     •  Prescrip9on  opioid  analgesics  are  an  important   component  of  modern  pain  management.     •  Abuse  and  misuse  of  these  products,  however,  have   created  a  serious  and  growing  public  health   problem.     •  FDA  has  worked  to  address  this  problem  while   ensuring  that  pa9ents  in  pain  have  appropriate   access  to  opioid  analgesics.    
  33. 33. Conflic9ng  Views   •  …  FDA  advisory  commiRee  voted  against  approval  of  a   hydrocodone  product  lacking  tamper-­‐resistant  technology.   –  "I  would  feel  very  uncomfortable  approving  a  non-­‐abuse-­‐ deterrent  product,"  one  of  the  panelists  said  at  the  9me.   •  Andrew  Kolodny,  MD,  co-­‐founder  of  PROP,  expressed  concern   that  labeling  of  abuse-­‐resistant  products  could  contribute  to   false  marke9ng.   –  "If  doctors  are  misled  to  believe  that  these  formula9ons  are   less  addic9ve,  and  if  they  develop  a  false  sense  of  security   about  these  products,  that  could  possibly  make  the  epidemic   worse,"   hRp://www.medpagetoday.com/PublicHealthPolicy/FDAGeneral/36782  
  34. 34. Abuse  Deterrent  Formula9ons  in  the  United  States   34 OxyContin, Opana ER, Exalgo, Oxecta, Nucynta ER
  35. 35. Abuse  Deterrent  Formula9ons   Site  of  Ac9on   35   Swallow   Chew   Crush   Snort   Inject   Currently   Available   Can  ADFs   Decrease   Progression?  
  36. 36. RADARS  System   Results  through  December  31,  2013   36   36
  37. 37. What  is  the  RADARS®  System?   •  History   –  Denver  Public  Safety  Net  Hospital  for  150  years   •  State  sanc9oned  independent  authority   –  Created  2001  by  Purdue  Pharma   –  2006,  Denver  Health  and  Hospital  Authority  (DHHA)   •  Independent  program   –  Mul9ple  pharmaceu9cal  subscribers   •  Data  can  only  be  used  for  safety  repor9ng   •  Conflict  of  interest  statement   –  None,  other  than  running  system  for  DHHA  as  noted   above   37  
  38. 38. Drug   Transactions   Criminal  Justice     250  agencies     49  states   Illicit  Market   Price   StreetRx.com   Users/Buyers   50  states   New   Initiates   College  Survey   2000  students     50  states     Entering   Treatment   SKIP   155  practices   47  states   Acute  Events   49  Poison                centers     46  states   Entering   Treatment   OTP   75  programs     37  states   Mosaic  Surveillance  for  Surveillance  of   Prescrip;on  Drug  Abuse  
  39. 39. 39   Principal  Inves;gators   •  Theodore  J.  Cicero,  PhD    Washington  University  at  St.  Louis   •  Richard  C.  Dart,  MD,  PhD    Denver  Health  and  Hospital  Authority   •  Hilary  SurraR,  PhD   Nova  Southeastern  University   •  Mark  W.  Parrino,  MPA    American  Associa=on  for  the      Treatment  of  Opioid  Dependence   Law  Enforcement   •  John  Burke    Na=onal  Associa=on  of      Drug  Diversion  Inves=gators   RADARS  System   Scien;fic  Advisory  Board   Substance  Abuse  Experts   •  Herbert  D.  Kleber,  MD    Columbia  University   •  Sidney  Schnoll,  MD,  PhD    Pinney  Associates   •  George  E.  Woody,  MD    University  of  Pennsylvania   Epidemiology/Biosta;s;cs   •  Edgar  Adams,  ScD   Covance   •  Nabarun  Dasgupta,  MPH    Founder  –  Epidemico   •  Alvaro  Muñoz,  PhD   Johns  Hopkins  University  
  40. 40. Show  Me  The  Data   •  Do  ADFs  decrease  abuse?   – OxyCon9n®  (polyethylene  oxide),  Opana  ER®   (Intac®),  Nucynta  ER  (Intac®)   – Exalgo®,  Oxecta®,  Embeda®   – Suboxone®,  buprenorphine/naloxone  combos   •  Do  they  affect  outcome?   – Injec9on?   – Mortality?  
  41. 41. RADARS  System     Schedule  II  Excluding  Oxycodone  ER  Popula9on   Rates  by  Program,  2009-­‐2013   41 0 1 2 3 4 5 20093 20094 20101 20102 20103 20104 20111 20112 20113 20114 20121 20122 20123 20124 20131 20132 20133 20134 Rateper100,000population Year Quarter Poison Center Program Drug Diversion Program Treatment Center Program College Survey Program
  42. 42. 42 Model  for  Oxycodone  Extended  Release   RADARS  System  Poison  Centers   0   2007   0.15   0.25   0.35   2005   0.30   0.20   0.10   0.05   2011  2010  2009   Inten9onal  exposures  /100,000  pop.     New Formulation All  Oxycodone  ER   95%  CI   Ineffective Effective October 21-22, 2010: Joint Meeting of the Anesthetic and Life Support Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee Meeting Announcement
  43. 43. ADFs–Demand  Reduc9on   People  Filling  Prescrip9ons   43 Before   AYer  ADF   AYer  ADF  Before   Oxycodone  ER   Oxymorphone  ER   Pre   Post  ADF   Pre   Post  ADF  
  44. 44. Drug  Diversion  Program   Popula9on  Rate,  2009-­‐2013   44  *Other  opioids  excluding  ER  oxycodone  and  ER  oxymorphone.     Oxycodone  ER   Oxymorphone  ER   Other  Opioids  
  45. 45. Poison  Center  Program   Popula9on  Rate,  2009-­‐2013   45  *Other  opioids  excluding  ER  oxycodone  and  ER  oxymorphone   Oxycodone  ER   Oxymorphone  ER   Other  Opioids  
  46. 46. Poison  Center  Program   Route  of  Administra9on,  OxyCon9n  
  47. 47. Rela9on  of  Original  OxyCon9n  and   Men9ons  in  Poison  Center  Program   Original  Formula;on  
  48. 48. Case  Outcome  in  Poison  Center  Program  -­‐   Major  Outcome  or  Death   0   0.005   0.01   0.015   0.02   0.025   0.03   0.035   0.04   0.045   0.05   Before  ADF   AUer  ADF   Before  ADF   AUer  ADF   OxyCon;n   Opana  ER   Rate  of  Major  Outcome  or  Death   Oxycodone  ER   Oxymorphone  ER  
  49. 49. Treatment  Programs  Combined   2009-­‐2013   49*Other  opioids  excluding  ER  oxycodone  and  ER  oxymorphone.     Oxycodone  ER   Oxymorphone  ER   Other  Opioids  
  50. 50. StreetRx.com   50
  51. 51. StreetRx, RADARS System Drug Diversion and Silk Road – Price per milligram drug 51 Dasgupta, Suratt, et al, J Med Internet Res, 2013
  52. 52. US  StreetRx   Endorsement  of  Canadian  Oxycodone  Products     in  United  States   52   11  States   1  to  4  reports  
  53. 53. Oxycodone  ER  in  US  and  Canada    Formula;on                                                                                                                            United  States   Canada   Number   reports   Reported  Median  Price   per  mg,  US  Dollar  (range)   Number   reports   Reported  Median     Price  per  mg,   Canadian  Dollar  (range)   Crushable  “Old  OxyCon;n”   Apo-­‐Oxycodone  CR     24   1.00   (0.15  –  16.80)   1   1.00   (NR)   OxyCon;n®   93   1.00   (0.06  –  10.00)     16   1.00   (0.54  –  6.00)   Co-­‐Oxycodone  CR   11   1.00   (0.30  –  4.00)   0   NR   Teva-­‐Oxycodone  CR   4   0.88   (0.10  –  3.75)   0   NR   Average   1.00   1.00    Abuse  Deterrent  “New  OxyCon;n”   Oxycodone  ER   (OxyCon;n  in  US,     OxyNEO  in  Canada)   277   0.63   (0.03  –  10.00)   15   0.75   (0.38  –  1.40)   Average   0.63   0.75   RADARS  System  Technical  Report,  2014-­‐Q2  
  54. 54. Other  Data  Sources   Navippro  Treatment  Centers   54   Butler  S,  et  al,  J  Pain  2012  
  55. 55. Other  Data  Sources   Na9onal  Survey  of  Drug  Use  and  Health   Good  News  –  Bad  News   “The  number  of  persons  aged  12  or  older  who  were   current  nonmedical  users  of  the  pain  reliever   OxyCon9n  declined  from  566,000  in  2010  to  358,000   in  2012.”   55   NSDUH  2013  
  56. 56. Yes,  Abuse  Deterrent  Formula9ons  Can   Reduce  the  Diversion  and  Abuse  of  an  Opioid   Analgesic,  but…   Some  Important  Ques9ons  Remain!   56  
  57. 57. Squeezing  the  Balloon   Heroin  -­‐  Past  Month,  Past  Year   NSDUH  Report  2012   ADF  Oxycodone  ER  
  58. 58. Can  ADFs  Bend  the  Curve?   •  CS  –  College  Survey  DD  –  Drug  Diversion   •  PC  –  Poison  Center  TC  –  Treatment  Centers  combined     •  Methadone,  buprenorphine,  liquids,  injectables  excluded   0 0.5 1 1.5 2 2.5 3 CS DD PC TC Rateper100,000population The RADARS System Average rate per 100,000 population by formulation 2013 ADF ER IR
  59. 59. Conclusions   •  Formula9ons  that  resist  crushing  and  forming   injectable  solu9ons  can  reduce  diversion,   abuse  and  the  sequelae  of  abuse  of  that   par9cular  drug.   •  The  poten9al  impact  of  ADF  technology  would   be  greater  if  more  products  used  technology.   •  However,  the  “market”  will  adjust  to  the  new   barriers.   59  
  60. 60. Thank  You!   60  

×