CENTER FoR DRuG EvALUATION AND RESEARCH 
Guidance  for  Industry 

The FDA published Good Guidance Practices in February 1997. 

This guidance was developed and issued prior to that date. 

Additional copies are available from: 

Office of Training and Communications 

Division of Communications Management 

Drug Information Branch, HFD-210 

5600 Fishers Lane 

Rockville, MD  20857 

(Tel) 301-827-4573 
(Internet)  http:llwww.fda.gov/cder/guidance/index.htm 
u.s. 
DEPARTMENT OF HEALTil AND HUMAN SERVICES, FOOD AND DRUG ADMINISTRATION  GUIDELINE FOR POSTMARKETING REPORTING OF 

ADVERSE DRUG EXPERIENCES 

OF 
U.S. DEPARTMENT  HEALTH AND HUMAN SERVICFS 

PUBLIC HEALTII SERVICE 

FOOD AND DRUG ADMINISTRATION 
 DEPARTMENT  OF  HEALTH  AND  HUMAN  SERVICES 

Food  and  Drug  Administration 

Center  for  Drug  Evaluation  and  Research 

GUIDELINE  FOR  POSTMARKETING  REPORTING  OF 

ADVERSE  DRUG  EXPERIENCES 

(Docket  No.  850-0249] 

March  1992  ,  . 

For  further  information  regarding  the  guideline,  please  contact: 
Food  and  Drug  Administration 

Center  for  Drug  Evaluation  and  Research 

Division  of  Epidemiology  and  Surveillance  (HFD-730) 

Room  15B-31,  5600  Fishers  Lane 

Rockville,  MD  20857 
 TABLE  OF  CONTENTS 
I.  Introduction 	
1 

II.  Scope 	
1 

.  .  .  .  . 
III.  Who  Must  Report 	 1 

.  .  .  .  .  . . 
IV. 	 What  to  Report  2 

15-Day  Reports  of  Serious,  Unlabeled  Events  2 

15-Day  Narrative  Increased  Frequency  Report  of  Serious, 

Labeled  Events  .  .  .  .  .  .  .  .  .  .  .  .    3 

Determination  of  15-Day  Reporting  Period  .  4 

Periodic  Reports  .  4 

Followup  Reports  .  7 

V. 	 How  and  Where  to  Report  8 

What  and  Where  to  Report  .  8 

How  To  Obtain  Copies  of  Form  FDA  1639  9 

Computerized  Forms  .  9 

Electronic  Submissions  .  .  10 

CIOMS  Forms  for  Foreign  Reports  .  10 

Questions  or  Comments  about  Reporting  Formats  .  10 

Questions  about  Determining  and  Reporting 

Increased  Frequencies  .  .  .  .  .  .  .  .  10 

Other  Questions  and  Comments  .  11 

VI. 	 Special  Situations  ..... .  .  11 

Scientific  Literature  Reports  .  11 

Postmarketing,  Clinical  Trial,  or  Surveillance 

Study  of  Drugs  Involving  ADE  Monitoring  .  .  .  .  .  .  .  12 

Foreign  Reports  .  12 

"Death"  Reports  .  .  .  .  13 

i  "Overdose"  Reports  .  .  .  13 
"Lack  of  Effect"  Reports  14 
Pediatric  Patients  ..  .  14 
Reporting  for  Prescription  Drugs  Marketed  Without  an  Approved 
NDA,  ANDA,  or  Antibiotic  Application  (21  CFR  310.305)  .  15 
Another  Applicant's  Drug  .  .  15 
Multiple  Suspect  Drugs  from  the  Same  Applicant  .  .  16 
Suspect  Drugs  with  Multiple  NDA's,  ANDA's,  or 
Antibiotic  Applications  by  the  Same  Applicant  .  16 
Unlabeled  Indications    16 
Drug  Interactions  .  16 
Product  Defects  17 
Internal  System  for  Monitoring,  Identifying,  and  Reporting 
Adverse  Events  .  .  .  .  .  .  .  .    .  .  .  .  .  .  .  .  .  .  17 
Labeling  Ambiguities  .  .  17 
Appendices: 
Appendix  A  Glossary  .  .  .  .  .  .  .  .  .    18 
Appendix  B  How  to  Complete  Form  FDA  1639  21 
Appendix  c  Fifteen-Day  Narrative  Increased  Frequency 
Report  of  Serious,  Labeled  Events  ..... 24 
Appendix  0  Sample  of  Transmittal  Letter  for 
Periodic  Report  .  .  .  .  29 
Appendix  E  Report  Checklist  30 
Appendix  F  Manufacturer  ADE  Reporting:  Spontaneous 
Domestic  Medical  Provider  or  Patient  .  .  .  33 
Appendix  G  Manufacturer  ADE  Reporting:  Foreign, 
Literature  or  Study  .  .  .            3 4 
Appendix  H  21  CFR  310.305  ..  35 
Appendix  I  21  CFR  314.80  .  38 
Appendix  J  Form  FDA  1639  (and  Instructions)      4 2 
ii  I.  Introduction 
Adverse  drug  experiences  (ADE's)  must  be  reported  in  accordance  with 
the  requirements  of  21  CFR  310.305  and  314.80. 
Those  regulations  require  three  types  of  ADE  reports:  (1)  15-day 
reports  of  serious,  unlabeled  events;  (2)  15-day  narrative  increased 
frequency  reports  of  serious,  labeled  events;  and  (3)  periodic 
reports.  This  guideline  has  been  developed  to  assist  applicants  in 
meeting  their  reporting  requirements. 
The  agency  advises  that  this  guideline  represents  its current 
position  on  the  requirements  for  reporting  of  ADE's.  This  guideline 
does  not  bind  the  agency,  and  it does  not  create  or  confer  an~ 
rights,  privileges,  or  benefits  for  or  on  any  persons. 
II.  Scope 
This  guideline  is  intended  to  assist  applicants  and  other  persons 
with  ADE  reporting  responsibilities  in  meeting  the  adverse 
experience  reporting  requirements  in  21  CFR  310.305  and  314.80. 
This  guideline  applies  to  each  ~pplicant having  an  approved 
abbreviated  or  full  application  under  21  CFR  Part  314.  In  addition, 
this guideline  applies  to  the  reporting  of  ADE's  under  21  CFR 
310.305  for  prescription drugs  not  subject  to  premarket  approval. 
This  guideline  does  not  apply  to  the  following  reports:.  (1) 
Investigational  new  drug  application  safety  reports  (21  CFR  312.32), 
(2)  safety update  reports  for  drugs  covered  by  a-pending .marketing 
application  (21  CFR  314.50(d) (5) (vi)),  and  product  defect  reports 
(21  CFR  314.81(b)).  This  guideline  also  does  not  provide  guidance 
on  the  annual  report  requirements  of  21  CFR  314.81(b) (2). 
III.  Who  Must  Report 
The  "manufacturer"  or  "applicant"  is  required  to  report.  In 
addition,  any  person  whose  name  appears  on  the  label  of  a  marketed 
drug  as  its manufacturer,  packer,  or  distributor has  reporting 
responsibilities,  as  does  the  individual  or  corporate  entity that 
holds  an  approved  new  drug  application  (NDA),  abbreviated  new  drug 
application  (ANDA),  or  antibiotic application.  For  purposes  of  this 
guideline,  "applicant"  includes  all  persons  with  reporting 
responsibility  under  21  CFR  310.305  and  314.80. 
1  IV. 	 What  to  Report 
To  summarize,  the  following  must  be  reported: 
(a) 	 All  reports  of  spontaneous  adverse  events  occurring  within 
the  United  States  (domestic  reports). 
(b) 	 Foreign,  literature,  and  study  reports  involving: 
(1}  Serious,  unlabeled  events; 

(2}  Increased  frequency  of  serious,  labeled  events. 

(Study  reports  must  only  be  submitted  if  there  is  "a  reasonable 
possibility  that  the  drug  caused  the  adverse  experience"  (21  CFR 
310.305(c) (1) (ii)  and  21  CFR  314.80(e) (1)) .) 
15-Day  Reports  of  Serious,  Unlabeled  Events 
Reports  of  serious,  unlabeled  events  must  be  reported  to  FDA  on  Form 
FDA  1639  as  soon  as  possible  but  in  any  case  within  15  working  days 
of  the  time  of  initial receipt  of  the  information  by  the  applicant. 
Submit  15-day  reports  in  duplicate  under  separate  cover  with  "15-Day 
Alert  Report"  marked  on  the  outside  envelope.  Multiple  15-day 
reports  and  followup  15-day  reports  may  be  submitted  in  the  same 
envelope,  though  they  should  not  be  stapled  together.  For  marketed 
prescription drugs  without  approved  NDA's,  ANDA's,  or  antibiotic 
applications,  15-day  reports  should  be  marked  "15-Day  Alert Report  
310.305"  and  a  single copy  sent. 
Note 	 that  outcome  (Form  FDA  1639,  Items  8-12,  and/or 
life-threatening,  congenital  anomaly,  overdose,  and  cancer)  must  be 
determined  before  a  report  can  be  identified  as  "serious." 
When  an  applicant  receives  information  that  should  be  submitted  in  a 
15-day  report,  but  it is  not  possible  to  provide  all  the  desired 
information  within  15  working  days,  a  preliminary  report  must  be 
submitted.  Additional  followup  information  must  be  sought  and 
submitted  within  15  working  days  after  obtaining  the  new 
information.  (See  "Followup  Reports"  section.) 
We  encourage  attachment  of  discharge  summaries,  autopsy  reports, 
relevant  laboratory  data,  and  other  concise  critical clinical data. 
DO  NOT  submit  a  copy  of  the  initial or  followup  15-day  report  (Form 
FDA  1639}  in  the  next  periodic  report. 
2  15-Day  Narrative  Increased  Freguency  Report  of  Serious,  Labeled 
Events 
Reports  of  an  increased  frequency  of  serious,  labeled  events  must  be 
reported  to  FDA  in  a  narrative  format  as  soon  as  possible,  but  in 
any  case  within  15  working  days  of  determining  that  a  significant 
increase  in  frequency  exists. 
For  each  adverse  event  reported  in  a  15-day  narrative  increased 
frequency  report,  a  Form  FDA  1639  should  be  completed.  Note  that 
only  Form  FDA  1639's  reporting  spontaneous  domestic  events  should  be 
included  in  the  periodic  report. 
For  foreign,  literature,  and  study  reports,  Form  FDA  1639's  should 
be  completed  but  they  should  not  be  included  in  the  periodic  report. 
They  should  only  be  attached  to  the  narrative  increased  frequency 
report  as  described .below. 
The  Form  FDA  1639  (including  spontaneous  domestic,  foreign, 
literature,  study,  etc.)  for  increased  frequency  cases  should  be 
attached  to  the  end  of  the  narrative  increased  frequency  report  and 
be  clearly marked  ''Duplicate  for  Increased  Frequency  Report." 
An  increased  frequency  can  be  determined  using  a  formula  (coupled 
with  a  table).  Using  the  formula  below,  an  increased  frequency 
exists  if the  number  of  reports  for  the  "report  interval"  is greater 
than  or  equal  to  the  critical  number  of  reports  "C"  which  is 
determined  from  the  numbers  of  reports  for  the  two  report  intervals 
and  the  estimated  drug  use  for  the  two  intervals  using  the  following 
formula: 
=  *  * 
C  (R  ~)  +  (1.645  ~ 
Where 	 Xc  is the  number  of  reports  for  the  "comparison  interval" 
Xr  is the  number  of  reports  for  the  "report  interval" 
R  is  the  marketing  ratio  of  the  "report  interval"  to  the 
"comparison  interval" 
* 
multiplication  sign 
The  marketing  ratio  is  defined  as: 
Estimated  drug  use  (e.g.,  number  of  prescriptions, 
unit  volumes,  sales,  etc.)  for  the  "report  interval" 
R  = 
Estimated  drug  use  (same  units  and  scope  as  in  the 
numerator)  for  the  "comparison  interval" 
]  Appendix  C  describes  in  more  detail  how  to  identify  an  increase  in 
frequency.  It  provides  a  sample  format  for  the  narrative  report  and 
examples  on  how  to  identify  an  increase  in  frequency  using  the 
formula  and  a  reference  table. 
Further,  note  that  no  increased  frequency  report  is  required  if  the 
number  of  reports  received  during  the  11 report  interval11  is  less  than 
four. 
Determination  of  15-Day  Reporting  Period 
Fifteen-day  reports  must  be  submitted  within  15  working  days  of  the 
time  (1)  of  initial  receipt  by  the  applicant  of  the  serious,  , 
unlabeled  status  of  the  event  or  (2)  of  determining  that an 
increase  in  frequency  of  a  serious,  labeled  event  has  occurred. 
(Refer  to  the  definition  of  11 serious"  in  Appendix  A.) 
Followup  information  for  15-day  reports  must  also  be  submitted 
within  15  working  days  of  its  receipt.  The  date  of  receipt  should 
be  entered  into  Item  24c.  of  Form  FDA  1639. 
For  foreign  reports,  the  15-day  time  clock  begins  when  the  applicant 
or  its  foreign  affiliate has  received  sufficient data  to  suggest 
that  15-day  criteria have  been  met  (based  on  u.s.  labeling  and 
definitions  of  serious  experience).  Applicants  must  therefore 
establish  effective  mechanisms  to  ensure  rapid  information  transfer 
from  their  foreign  affiliates. 
Periodic  Reports 
Periodic  reports  are  required  for  each  approved  NDA,  ANDA,  and 
antibiotic application.  Periodic  reports  are  due  quarterly  for  the 
first  3  years  after approval,  and  annually  thereafter.  If marketing 
is delayed,  these  reports  should  also  be  submitted  quarterly  for  the 
first  3  years  of  marketing. 
Periodic  reports  due  quarterly  must  be  submitted  within  30  days  of 
the  last day  of  the  reporting  quarter.  Reports  due  annually  must  be 
submitted  each  year  within  60  days  of  the  anniversary  date  of 
approval  of  the  drug. 
Upon  written  notice,  FDA  may  extend  or  reestablish  the  requirement 
that an  applicant  submit  quarterly  reports  or  require  that  the 
applicant  submit  reports  under  21  CFR  314.80(c) (2)  at different 
times. 
A  periodic  report  must  contain  the  following  four  components 
described  below.  Each  should  be  clearly  separated  by  an  identifying 
tab  and  arranged  in  the  following  order: 
4  1.  Form  FDA  1639's  for  serious,  labeled  and  nonserious 
(labeled  and  unlabeled)  ADE's  from  spontaneous,  domestic  sources. 
(Form  FDA  1639's  for  serious,  unlabeled  experiences  should  not  be 
included  in  the  periodic  report  since  they  should  have  been 
previously  submitted  as  15-day  reports.) 
A  separate  Form  FDA  1639  must  be  completed  for  followup  as  well 
as  for  initial  reports  for  each  individual  person  experiencing  an 
adverse  event. 
It may  not  be  necessary  to  include  attachments  with  the 
submitted  Form  FDA  1639's.  However,  discharge  summaries  and  other 
concise  critical data  are  encouraged  if  they  help  to  explain  the 
adverse  experience. 
Initial  Form  FDA  1639's  should  be  separated  from,followup  Form 

FDA  1639  reports. 

The  applicant  should  not  submit  initial and  followup  Form  FDA 

1639's  on  the  same  case  in  the  same  periodic  report.  All  initial 

and  followup  information  should  be  combined  and  submitted  as  one 

initial  Form  FDA  1639. 

Note  that  adverse  experiences  include  reports  of  failure  to 

produce  the  expected  pharmacologic  action,  i.e.,  ''lack  of  effect." 

2.  Index  line  listing of  Form  FDA  1639's  included  in  "1" 

above.  A  line  listing  for  each  Form  FDA  1639  submitted  should 

include: 

a.  Manufacturer  control  number. 
b.  Adverse  event(s). 
c.  Page  number  of  the  individual  Form  FDA  1639  as  located  in 

the  periodic  report. 

Also,  for  any  "drug  interaction''  listed as  an  adverse  event, 

the  interacting drugs  should  be  identified  in  the  periodic  report 

line  listing. 

3.  Narrative  summary  and  analysis  of  the  information  in the 

periodic  report  and  an  analysis  of  the  15-day  reports  submitted 

during  the  reporting  period. 

This  section  should  include: 
a.  Listing  of  the  15-day  reports  of  serious,  unlabeled 
experiences  submitted  during  the  period.  This  listing  should 
include  manufacturer  control  number,  adverse  event(s),  and  date  sent 
to  FDA. 
5 
 b.  Listing  of  the  15-day  increased  frequency  narrative 
reports  of  serious,  labeled  events  submitted  during  the  period. 
This  listing  should  include  the  adverse  event(s)  and  date  sent  to 
FDA. 
c.  Listing  by  body  system  of  all  ADE  terms  and  counts  of 
occurrences  submitted  during  the  period  (taken  from  the  15-day 
reports  of  serious,  unlabeled  experiences  and  the  Form  FDA  1639's 
submitted  in  the  periodic  report). 
For  the  ADE  term  "drug  interaction,"  the  interacting drugs 
should  be  identified  in  the  tabulation. 
d.  Summary  of  the  ADE  reports  in which  the  drug  was  listed as 
one  of  the  suspect  drugs,  but  the  report  was  filed  to  another  NDA  or 
ANDA  held  by  the  applicant. 
e.  Narrative  discussion  of  the  clinical significance of  the 
15-day  reports  (reports  of  serious,  unlabeled  events  and  increase  in 
frequency  of  serious,  labeled  events).  This  narrative  should  assess 
clinical  significance  by  type  of  event,  body  system,  and  overall 
drug  safety  relating  the  new  information  received  during  this period 
to  what  was  already  known  about  the  drug. 
4.  Narrative  discussion  of  action  taken,  including  labeling 

changes  and  studies  initiated since  the  last periodic  report. 

The  "narrative  of  action  taken"  section  should  include  the 

following: 

a.  A  copy  of  current  product  labeling. 
b.  A  listing of  any  labeling changes  made  during  the period. 
c.  Studies  initiated. 
d.  Summary  of  important  foreign  actions;  e.g.,  new  warnings, 
limitations  in  the  indications  and  use  of  the  product. 
e.  Communication  of  new  safety  information;  e.g.,  a  "Dear 

Doctor"  letter. 

If  information  for  one  of  these  tabs  is  not  included,  an  explanatory 
note  must  accompany  that  section  of  the  report. 
Each  page  of  the  periodic  report  should  be  numbered  and  include  the 
name  and  NDA  number  of  the  drug. 
Each  copy  of  the  periodic  report  should  be  covered  by  a  transmittal 
letter,  which  includes  the  drug  name,  NDA  number,  time  period 
covered,  number  of  initial  periodic  ADE  reports  (Form  FDA  1639) 
6  contained  in  the  submission,  and  number  of  followup  periodic  ADE 
reports  (Form  FDA  1639)  contained  in  the  submission.  Data  from  the 
Form  FDA  1639's  should  not  be  included  in  the  transmittal  letter. 
(See  Appendix  D  for  a  sample  transmittal  letter.) 
If  no  adverse  experiences  were  identified  for  the  period  involved 
and  no  actions  taken,  a  transmittal  letter  stating  this  must  be 
submitted  along  with  a  copy  of  the  current  labeling. 
Periodic  submissions  must  be  clearly  marked  "Periodic ADE 
Submission"  on  the  front  cover  of  each  volume. 
Followup  Reports 
A  followup  report  provides  information  about  an  event  that has  been 

reported  previously  as  an  initial  report  with  a  unique  manufacturer 

control  number  (Item  24b,  Form  FDA  1639). 

A  followup  report  should  provide  a  complete  picture  of  the  current 
understanding  of  the  adverse  experience.  Information  in  the  initial 
report  should  be  combined  with  the  followup  information  to  present  a 
true  and  comprehensive  description  of  the  adverse  experience  as  it 
is  understood  at  the  time  of  the  followup.  Information  from  the 
initial  report  later  found  to  be  inaccurate  should  not  be  repeated 
in  the  followup.  Thus,  it should  not  be  necessary  to  send  the 
initial  Form  FDA  1639  with  the  followup  Form  FDA  1639. 
The  followup  report  should  include: 
Correct  information  contained  in  the  initial  report  plus  the 
new  data.  The  new  data  should  be  marked  (e.g.,  with  an  asterisk, 
highlighted,  underlined,  etc.).  Any  attachments  submitted  in  the 
initial  report  (e.g.,  journal  articles,  discharge  summaries)  should 
not  be  resubmitted. 
Item  24b  - The  same  unique  manufacturer  control  number  used  on 
the  initial  report;  this  is  essential  to  prevent  duplicate  counting 
of  reports. 
Item  24c  - The  date  the  followup  information  was  received  by 

the  applicant. 

Item  25a- Clearly  marked  "followup." 
To  summarize,  the  followup  report  (and  attachments,  if any)  must 
contain  the  applicant's  same  unique  internal  recordkeeping  number 
(control  number,  Item  24b  on  Form  FDA  1639)  as  the  initial  report. 
If  the  initial  report  was  submitted  as  a  15-day  report,  the  followup 
report  should  be  submitted  as  a  15-day  followup  report  even  if  the 
followup  information  shows  that  the  event  was  labeled  or  not 
7  serious.  Conversely,  a  15-day  followup  report  should  be  submitted 
if  the  event  is  found  to  be  serious  and  unlabeled,  even  if  the 
original  report  was  not  submitted  as  a  15-day  report. 
DO  NOT  submit  a  followup  report  if  additional  relevant  information 
is  not  obtained.  However,  the  documentation  of  the  procedure 
followed  in  seeking  to  obtain  the  additional  information  should  be 
maintained.  FDA  may  request  this  documentation. 
Fifteen-day  followup  reports  should  not  be  submitted  in  the  same 
envelope  with  periodic  reports.  "15-Day  Alert  Report"  should  be 
marked  on  the  outside  envelope  of  the  15-day  followup  reports. 
DO  NOT  submit  a  followup  report  when  reporting  a  different 
experience  in  a  patient  for  whom  a  previous  experience  was  reported 
and  submitted.  Submit  an  initial  report  with  a  new  control  number 
(Item  24b)  on  a  Form  FDA-1639  for  a  new,  subsequent  experience. 
Thus,  a  followup  report  follows  an  experience,  not  a  patient 
... 
v. 
How  and  Where  to  Report 
What  and  Where  to  Report 
For  prescription drugs  without  approved  NDA's,  ANDA's,  or 

antibiotic applications,  adverse  experience  reports  should  be  sent 

as  single  copies  to: 

Division  of  Epidemiology  and  Surveillance  (HFD-730) 
Center  for  Drug  Evaluation  and  Research 
Food  and  Drug  Administration 
5600  Fishers  Lane 
Rockville,  MD  20857 
For  drugs  with  approved  NDA's,  ANDA's,  or  antibiotic 
applications,  all  15-day  Form  FDA  1639  reports  of  serious,  unlabeled 
events;  15-day  narrative  increased  frequency  reports  of  serious, 
labeled  events;  periodic  reports;  followup  reports,  and  letters 
stating  no  reports  were  received  during  the  reporting  period  should 
be  sent  in  duplicate  to: 
Central  Document  Room 
Food  and  Drug  Administration 
Park  Building,  Room  214 
12420  Parklawn  Drive 
Rockville,  MD  20857 
All  submissions  must  be  legible,  preferably  typewritten. 
Legible  photostatic  copies  are  acceptable.  However,  visual  contrast 
must  be  adequate  to  assure  clear  readable  microfilm  copies. 
8  If  the  applicant  becomes  aware  of  a  reportable  adverse  event 
' 
the  applicant  is  responsible  for  transferring  the  information  to  a 
Form  FDA  1639  (and  narrative  increased  frequency  report  if 
indicated)  and  submitting  it to  FDA.  If  it  is  a  serious,  unlabeled 
event,  the  Form  FDA  1639  should  be  submitted  within  15  days.  The 
applicant  should  not  assume  the  reporting  requirements  are  fulfilled 
by  asking  the  initial  reporter  to  return  a  Form  FDA  1639  to  the 
applicant  or  FDA.  The  applicant  should  not  wait  for  the  reporter  to 
complete  a  Form  FDA  1639  before  submitting  a  report  of  a  serious, 
unlabeled  event  to  FDA.  A  15-day  report  can  and  should  be  submitted 
based  only  on  verbal  information. 
All  ADE  reports,  except  15-day  narrative  increased  frequency 
reports,  should  be  reported  on  a  Form  FDA  1639.  (Detailed  . 
guidelines  for  narrative  increased  frequency  reports  are  in Appendix 
c.) 
How  To  Obtain  Copies  of  Form  FDA  1639 
To  obtain  up  to  10  copies  of  Form  FDA  1639  write  to: 
Division  of  Epidemiology  and  Surveillance  (HFD-730) 
Food  and  Drug  Administration 
5600  Fishers  Lane,  Room  158-31 
Rockville,  MD  20857 
Additional  copies  can  be  obtained  from: 
PHS  Forms  and  Publications  Distribution Center  (HFA-268) 
12100  Parklawn  Drive 
Rockville,  MD  20852 
Copies  of  blank  Form  FDA  1639  can  also  be  duplicated  by  the 

applicant. 

Computerized  Forms 
In  lieu of  using  the  preprinted  Form  FDA  1639,  a 
computer-generated  report  may  be  submitted  if  it contains  all of  the 
elements  of  information  in  the  identical  enumerated  sequence  of  Form 
FDA  1639,  is  completed  in  accordance  with  this  guideline,  and  is 
forwarded  with  the  appropriate  number  of  copies.  The  typeset must 
be  large  and  clear  enough  to  assure  readable  microfilm  copies. 
Each  applicant's  use  of  a  modified  form  must  be  preapproved  by 
FDA  in  writing. 
9  Electronic  Submissions 
Electronically  produced  adverse  drug  experience  reports  may  be 
submitted;  however,  each  applicant  must  obtain  prior  written 
approval. 
At  this  time,  only  periodic  reports  may  be  submitted 
electronically.  Fifteen-day  reports  (serious,  unlabeled  events  and 
an  increase  in  frequency  of  serious,  labeled  events)  may  not  be 
submitted  electronically.  Also,  followup  reports  (to  both  15-day 
and  non-15-day  reports)  may  not  be  submitted  electronically. 
CIOMS  Forms  for  Foreign  Reports 
The  Council  for  International  Organizations  for  Medical 
Sciences  (CIOMS),  working  with  several  member  nations  and  industry, 
has  developed  a  format  (resembling  Form  FDA  1639)  for  international 
ADE  reporting.  With  prior written  approval,  this  format  can  be  used 
for  reporting  foreign  adverse  experiences  to  the  u.s.  Food  and  Drug 
Administration. 
Questions  or  Comments  about  Reporting  Formats 
Requests  for  approval  of  reporting  formats  (computerized  forms, 
electronic  submissions,  CIOMS  formats,  etc.)  should  be  addressed  to: 
Surveillance and  Data  Processing  Branch  (HFD-737) 
Division  of  Epidemiology  and  Surveillance 
Food  and  Drug  Administration 
5600  Fishers  Lane 
Rockville,  MD  20857 
Phone:  301-443-6414 
Questions  about  Determining  and  Reporting  Increased  Freguencies 
Questions  about  determining  increased  frequencies  should  be 
addressed  to: 
Epidemiology  Branch  (HFD-733) 
Division  of  Epidemiology  and  surveillance 
Food  and  Drug  Administration 
5600  Fishers  Lane 
Rockville,  MD  20857 
Phone:  301-443-2306 
10  Other  Questions  and  Comments 
General  questions  or  comments  about  this  guideline  or  ADE 
reporting  should  be  addressed  to: 
Reports  Evaluation  Branch 
Division  of  Epidemiology  and  Surveillance  (HFD-735) 
Food  and  Drug  Administration 
5600  Fishers  Lane 
Rockville,  MD  20857 
Phone:  301-443-4580 
VI.  Special  Situations 
A  number  of  special  situations  occur  that  may  seemingly 

complicate  reporting  requirements.  Following  are  several: 

a.  Scientific  Literature  Reports 
Serious,  unlabeled  adverse  events  that  are  reported  in  the 

literature  (or  as  an  unpublished  manuscript)  must  be  submitted  as 

15-day  reports  on  Form  FDA  1639. 

A  copy  of  the  article  or  manuscript  must  be  attached  to  the 

completed  Form  FDA  1639. 

A  separate  Form  FDA  1639  must  be  completed  for  each 
identifiable  patient  (with  an  identifiable adverse  event).  Thus,  if 
an  article describes  six  patients with  a  given  adverse  experience, 
six  Form  FDA  1639's  should  be  completed. 
When  an  ADE  is  based  on  a  foreign  language  article  or 

manuscript,  the  applicant  is  expected  to  translate  the  publication 

into  English  promptly.  The  original  article or  manuscript  and 

translation  should  be  attached  to  the  submitted  Form  FDA  1639. 

All  literature  reports  and  manuscript  reports  should  be  marked 
"Literature"  in  Item  24d. 
If multiple  drug  products  are  mentioned  in  the  article,  Form 
FDA  1639  should  be  submitted  only  by  the  manufacturer  whose  drug  is 
the  suspect  drug. 
The  suspect  drug  is  that  identified  by  the  article's author, 

and  is  usually  mentioned  in  the  article's  title. 

11  b. 	 Postmarketing,  Clinical  Trial,  or  Surveillance  Study  of  Drugs 
Involving  ADE  Monitoring 
For  the  purposes  of  this  section,  a  study  refers  to  a  formal 
research  effort  including  a  protocol  with  specific  objectives  and  a 
scientific methodology  for  collecting  and  analyzing  ADE  data. 
Anything  less  rigorous  should  be  treated  as  a  spontaneous  report. 
The  only  experiences  from  studies  that  should  be  considered  for 
submission  to  FDA  under  21  CFR  310.305  or  314.80  are  those  that 
would  be  reported  as  (1)  15-day  reports  of  serious,  unlabeled  events 
and  (2)  15-day  narrative  increased  frequency  reports  of  serious, 
labeled  events.  These  should  be  reported  only  if  there  is  a 
"reasonable  possibility"  that  the  event  is  causally  related  to  the 
drug  exposure. 
Events  reportable  from  investigational  new  drug  (TND)  trials 
(with  marketed  drugs)  also  must  be  submitted  to  the  IND  as  described 
in  21  CFR  312.32. 
For  each  ADE,  a  suspect  drug  must  be  identified.  Thus,  for 

blinded  studies,  reports  shall  be  completed  only  after  the  code  is 

broken. 

Postmarketing,  clinical  trial,  and  surveillance  studies  as 
described  in  this  section  and  under  21  CFR  310.305  or  314.80(e) 
refer  to  studies  specifically monitoring  adverse  effects  of  the 
drug.  Adverse  events  incidental  to  other  types  of  studies  should  be 
treated  as  spontaneous  reports. 
c. 	 Foreign  Reports 
Only  15-day  reports  of  serious,  unlabeled  events  and  15-day 
narrative  increased  frequency  reports  of  serious,  labeled  events  are 
required  to  be  submitted  with  respect  to  foreign  reports.  Other 
foreign  reports,  including  serious,  labeled  events  and  all 
nonserious  events,  are  not  required  to  be  submitted.  However, 
reports  of  serious,  labeled  events  should  be  available  and  submitted 
to  FDA  if  requested. 
Reports  are  also  to  be  submitted  if  the  foreign  ADE  is  for  a 

product  that  has  the  same  active  moiety  as  the  product  marketed  in 

the  United  States.  This  is  true  even  if  the  excipients,  dosage 

forms,  strengths,  routes  of  administration,  and  indications  vary. 

When  a  foreign  report  is  submitted  on  a  product  that  is  not 
identical  to  the  product  marketed  in  the  United  States,  Item  24a 
should  contain  the  foreign  trade  name,  the  generic  name  of  the  same 
active  moiety  as  marketed  in  the  United  States,  and  should  read, 
"similar  to  NDA  number  " 
12 
 When  determining  whether  there  has  been  an  increased  frequency 
of  an  ADE  using  foreign  reports,  the  denominator  should  be  the 
foreign  drug  use  data. 
d.  "Death"  Reports 
Because  death  is  always  a  serious  outcome,  if  death  is 
associated  with  an  unlabeled  event,  or  if  death  is  associated  with  a 
labeled  event  and  the  labeling  does  not  specify  that  the  event  may 
be  associated  with  a  fatal  outcome,  a  15-day  report  should  be 
submitted  on  a  Form  FDA  1639. 
Each  report  involving  death  is  analyzed  for  an  increase  in 

frequency  in  two  distinct ways. 

For  one  analysis,  death  reports  associated  with  a  given  labeled 
event  should  be  combined  with  other  serious  reports  of  that 
particular  event,  and  are  analyzed  periodically  (at  least quarterly 
for  the  first  3  years  of  marketing  and  annually  thereafter)  for  an 
increase  in  frequency. 
For  the  other  analysis,  unlabeled  death  reports,  labeled death 
reports,  and  reports  of  "death  only"  are  combined  and  analyzed  for 
an  increase  in  frequency.  ("Death  only''  reports  are  those  reporting 
death  with  no  other  specific  adverse  event.) 
For  an  increase  in  frequency  assessment,  analyze  together  only 
reports  from  a  single  source  type  (e.g.,  compare  spontaneous  reports 
with  spontaneous  reports;  compare  study  reports  with  reports  from 
comparable  studies;  do  not  combine  spontaneous  reports  with  study 
reports;  do  not  combine  foreign  reports  with  domestic  reports).  If 
an  increase  in  frequency  is detected,  a  15-day  narrative  increased 
frequency  report  should  be  submitted. 
Spontaneous  domestic  reports  of  "death  only"  should  be  included 
in  the  periodic  report. 
e.  "Overdose"  Reports 
Reports  of  overdose  should  be  submitted  only  when  the  overdose 
was  associated  with  an  adverse  event.  The  adverse  experiences 
associated  with  the  overdose  should  be  reported  as  are  other  serious 
reactions.  If  the  event  is  unlabeled,  a  15-day  Form  FDA  1639  should 
be  completed;  if the  event  is  labeled,  a  Form  FDA  1639  should  be 
submitted  in  the  periodic  report  for  spontaneous  domestic  cases. 
overdose  reports  associated  with  a  given  labeled  event  should 
be  combined  with  other  serious  reports  of  that  particular  event  and 
should  be  analyzed  periodically  (at  least  quarterly  for  the  first  3 
13 
 years  of  marketing  and  annually  thereafter)  for  an  increase  in 
frequency. 
For  an  increase  in  frequency  assessment,  only  analyze  reports 
for  that  event  from  a  single  source  type  (e.g.,  compare  spontaneous 
reports  with  spontaneous  reports;  compare  study  reports  with  reports 
from  comparable  studies;  do  not  combine  spontaneous  reports  with 
study  reports;  do  not  combine  foreign  reports  with  domestic 
reports) .  If  an  increase  in  frequency  is  detected,  a  15-day 
increased  frequency  narrative  report  should  be  submitted.  (Note 
that  an  increased  frequency  analysis  is  not  required  for  all 
overdose  reports,  combining  events.) 
f.  "Lack  of  Effect"  Reports 
"Failure  to  produce  the  expected  pharmacologic  action"  is 
synonymous  with  "lack  of  effect." 
All  spontaneous  domestic  reports  of  "lack  of  effect"  should  be 

reported  on  Form  FDA  1639  and  submitted  in  the  periodic  report with 

other ADE's.  The  lot  number  of  the  suspect  drug  should  be  included 

in  Item  14. 

These  reports  should  be  analyzed  (at  least quarterly  for  the 

first  3  years  of  marketing;  annually  thereafter)  for  an  increase  in 

frequency.  For  drugs  with  multiple  indications,  ''lack  of  effect" 

should  also  be  analyzed  separately  for  each  indication.  If an 

increase  in  frequency  is detected,  a  narrative  report  should  be 

submitted  within  15  days  of  detection. 

Spontaneous  reports  of  "lack  of  effect"  should  be  analyzed 
separately  from  study  reports  for  an  increase  in  frequency.  Foreign 
"lack  of  effect"  reports  should  be  neither  reported  nor  analyzed  for 
an  increase  in  frequency. 
If  the  report  of  "lack of  effect"  is  for  an  unapproved 
indication,  the  event  is  not  reportable.  However,  this  information 
may  be  included  in  the  narrative  summary  section  of  the- periodic 
report. 
g.  Pediatric  Patients 
For  children  under  5  years  of  age: 
Item  1:  Include  the  child's date  of  birth. 
Item  2:  Write  age  as  days,  weeks,  or  months,  e.g.,  "15 

weeks;"  make  certain  that  "days, ..  "weeks,"  or  "months"  is  clearly 

written. 

14 
 For  all  pediatric  patients,  include  body  weight  and  dose  (Item 
15} . 
For  reports  of  congenital  anomaly: 
Give  age  and  sex  of  the  infant. 
Followup  reports  for  the  infant  should  be  considered  followup 
to  the  initial  report. 
Followup  for  the  mother  will  be  a  new  initial case 
consid~red 
report  on  a  separate  Form  FDA  1639. 
The  birth date  or  date  pregnancy  is  terminated  should  be  the 
event  onset  date. 
h.  Reporting  for  Prescription  Drugs  Marketed  Without  an  Approved 
NDA,  ANDA,  or  Antibiotic  Application  (21  CFR  310.305) 
For  marketed  prescription drugs  without  an  approved  NDA,  ANDA, 
or  antibiotic  application,  all  serious,  unlabeled  ADE's  must  be 
reported  on  Form  FDA  1639  within  15  working  days;  narrative 
increased  frequency  reports  of  serious,  labeled  events  must  also  be 
submitted  within  15  working  days. 
These  reports  should  be  submitted  in  SINGLE  copy  under  separate 
cover with  the  outside  envelope  labeled,  ''15-Day  Alert  Report"  and 
"310.305." 
A  copy  of  product  labeling  should  accompany  each  report. 
i.  Another  Applicant's  Drug 
Reports  of  ADE's  in which  the  initial  reporter  identifies  the 
suspect drug  as  one  marketed  by  another  applicant  should  be  promptly 
forwarded  to  that applicant.  Such  reports  should  NOT  be  reported  to 
the  agency  by  the  applicant  to  whom  the  ADE  was  originally reported. 
An  applicant  who  receives  such  a  report  about  its drug  from 
another  applicant  is  required  to  submit  the  report  to  FDA  with  the 
time  constraints  applicable  to  any  other  report  received  from  a 
third  party. 
An  exception  to  this  is when  serious,  unlabeled  experiences  are 
found  for  another  applicant's  drug  during  the  conduct  of  an  IND 
study  of  a  marketed  drug.  In  this  instance,  such  reports  may  be 
submitted  directly  to  FDA  by  the  applicant  conducting  the  study. 
15 
 j.  Multiple  Suspect  Drugs  from  the  Same  Applicant 
If  a  reportable  event  involves  two  or  more  drugs  from  the  same 
manufacturer,  only  one  Form  FDA  1639  should  be  completed.  It should 
be  submitted  to  the  NDA,  ANDA,  or  antibiotic  application  considered 
"most  suspect"  by  the  initial  reporter.  If  they  are  ranked  equally, 
the  report  should  be  submitted  to  the  drug  first  in  alphabetical 
order. 
The  adverse  event  is  also  reported  in  the  narrative  summary 
portion  of  the  periodic  report  of  the  other  drug(s). 
k.  suspect  Drugs  with  Multiple  NDA's,  ANDA's,  or  Antibiotic 
Applications  by  the  Same  Applicant 
A  drug  product  may  be  the  subject  of  more  than  onaapproved 
NDA,  ANDA,  or  antibiotic  application.  This  section  applies  to  this 
situation. 
If  an  applicant  receives  a  report  for  a  drug  and  the  specific 
application  is  identifiable,  the  report  should  be  submitted  to  that 
application. 
If  a  drug  has  more  than  one  application,  and  it cannot  be 
determined  which  of  the  approved  applications  is  involved,  the 
report  should  be  submitted  to  the  application  that  was  approved 
first  (usually  the  one  with  the  lowest  application  number). 
For  drugs  having  more  than  one  application due  to  different 
dosages,  reports  should  be  analyzed  for  an  increase  in  frequency  for 
each  individual  dosage  as  well  as  all dosages  combined. 
1.  Unlabeled  Indications 
An  adverse  experience  associated with  the  use  of  a  drug  for  an 
unapproved  indication  should  be  reported  as  any  other  adverse  event: 
15-day  report  of  a  serious,  unlabeled  event  on  Form  FDA  1639;  15-day 
narrative  increased  frequency  report;  or  the  periodic  report. 
"Lack  of  effect''  for  an  unlabeled  indication,  however,  should 
not  be  reported  on  a  Form  FDA  1639  nor  used  in  increased  frequency 
calculations;  such  information  may  be  included  in  the  narrative 
summary  section  of  the  periodic  report. 
m.  Drug  Interactions 
If  an  applicant  receives  a  report  classified  as  a  drug 
interaction,  each  of  the  drugs  must  be  identified  in  Item  14  as  a 
suspect  drug. 
16 
 n.  Product  Defects 
If  a  product  defect  results  in  an  adverse  experience,  the 
adverse  event  should  be  reported  as  described  in  this  guideline. 
o.  Internal  System  for  Monitoring,  Identifying,  and  Reporting 
Adverse  Events 
Each  applicant  should  develop  standardized,  formal  procedures 
for  the  surveillance,  receipt,  evaluation,  and  reporting  of ADE's  to 
FDA.  As  a  ,general  rule,  FDA  will  consider  an  applicant  responsible 
for  information  known  to  its employees  and  agents.  All  applicants 
should  develop  procedures  that  allow  expedited  report  handling,  and 
the  applicant  should  keep  on  file  documentation  of  due  diligence. 
This  applies  to  both  domestic  and  international  surveillance  for, 
and  processing  of,  ADE's. 
p.  Labeling  Ambiguities 
In  some  cases,  it may  be  difficult  to  decide  whether  or  not  the 
reported  experience  is  labeled.  In  these  situations,  the  event 
should  be  considered  unlabeled. 
17 
 APPENDIX  A 

GLOSSARY 

AFFILIATE  - Any  corporate  entity  related  to  the  applicant, 
including  all  subsidiaries,  licensees,  licensors,  etc. 
APPLICANT- Entity  who  holds  the  new  drug  application  (NDA), 
abbreviated  new  drug  application  (ANDA),  or  antibiotic 
application,  and  is  thus  required  to  report  adverse  drug 
experiences.  For  purposes  of  this guideline,  this  term  includes 
manufacturers,  packers,  and  distributors  of  the  drug  product. 
CAUSALITY  ASSESSMENT  - Determination  of  whether  there~is 
reasonable  possibility that  the  drug  is  etiologicallyrelated to 
the  adverse  event.  Causality  assessment  includes,  for  example, 
assessment  of  temporal  relationships,  dechallengejrechallenge 
information,  association  with  (or  lack  of  association  with) 
underlying  disease,  presence  (or  absence)  of  a  more  likely cause, 
plausibility,  etc. 
CHALLENGE  - Administration  of  a  suspect  drug  by  any  route. 
DECHALLENGE  - Withdrawal  of  a  drug  from  the  patient's 
therapeutic  regimen. 
NEGATIVE  DECHALLENGE  - Continued  presence  of  an  adverse 
experience  after withdrawal  of  the  drug. 
POSITIVE  DECHALLENGE  - Partial  or  complete  disappearance  of 
an  adverse  event  after withdrawal  of  the  drug. 
RECHALLENGE  - Reintroduction  of  a  drug  suspected  of  having 
caused  an  adverse  event  following  a  positive dechallenge. 
NEGATIVE  RECHALLENGE  - Failure  of  the  drug,  when 
reintroduced,  to  produce  signs  or  symptoms  similar  to  those 
observed  when  the  drug  was  previously  introduced. 
POSITIVE  RECHALLENGE  - Reoccurrence  of  similar  signs  and 
symptoms  upon  reintroduction  of  the  drug. 
EXPERIENCE  - Synonymous  with  adverse  drug  experience,  adverse 

experience,  adverse  drug  event,  adverse  event. 

ADVERSE  DRUG  EXPERIENCE  (ADE)  - Any  undesirable  event  that 
is  associated  with  the  use  of  a  drug  in  humans,  whether  or 
not  considered  drug-related  by  the  applicant.  Reporting  an 
adverse  experience  does  not  necessarily  reflect  a  conclusion 
18 
 APPENDIX  A--CONTINUED 

by  the  applicant  or  FDA  that  the  event  is  causally  related 
to  the  drug. 
EXPECTED  (LABELED)  EXPERIENCE  - Event  is  listed  in  the 
current  FDA-approved  labeling  for  the  drug  as  a  possible 
complication  of  drug  use. 
UNEXPECTED  (UNLABELED)  EXPERIENCE  - Event  is  not  listed  in 
the  current  FDA-approved  labeling  for  the  drug.  This 
includes  an  event  that may  differ  from  a  labeled  reaction 
because  of  greater  severity  or  specificity  (e.g.,  abnormal 
liver  function  versus  hepatic  necrosis) .  Events  listed as 
occurring  with  a  class  of  drugs  but  not  specifically 
mentioned  with  a  particular drug  are  considered  unlabeled. 
(For  example,  rash  with  antibiotic  X would  be  unlabeled  even 
if the  labeling  said  "rash  may  be  associated with 
antibiotics."  This  is  because  the  labeling  does  not 
specifically state  "rash  is  associated  with  antibiotic  X.") 
Reports  of  death  from  an  adverse  event  are  considered 
unlabeled  unless  the  possibility of  a  fatal  outcome  from 
that  adverse  event  is  stated  in  the  labeling. 
INCREASED  FREQUENCY  - Increase  in  the  rate  of  reporting  for  an 
adverse  drug  experience  or  related  events  during  a  specified time 
period  (after  adjustment  for  drug  marketing  data  or  number .of. 
patients  exposed)  when  compared  to  the  adjusted  rate  for  similar 
reports  during  a  previous  period. 
INITIAL  REPORTER  - The  original  source  of  the  information 
submitted  by  the  applicant  on  Form  FDA  1639. 
REPORT  - A  submission  to  FDA  as  described  in  this guideline. 
ANNUAL  REPORT  - Contains  information  described  in  21  CFR 
314.81  and  is  NOT  addressed  in  this guideline. 
FIFTEEN-DAY  REPORT  - Fifteen-day  reports  must  be  submitted 
within  15  working  days  of  the  time  (1)  of  initial  receipt  by 
the  applicant  of  the  serious,  unlabeled  status  of  the  event 
or  (2)  of  determining  that  an  increase  in  frequency  of  a 
serious,  labeled  event  has  occurred. 
PERIODIC  REPORT  - The  four-part  report  described  in  the  text 
of  this  guideline  and  in  the  regulations. 
SERIOUS  - An  adverse  drug  experience  that  is  associated  with: 
Death; 
19 
 APPENDIX  A--CONTINUED 
Initial  inpatient  hospitalization; 

Prolongation  of  hospitalization; 

Permanent  or  severe  disability  - permanent  or  severe 

disruption  in  one's  ability  to  carry  out  normal  life 

functions; 

A  life-threatening  situation  - the  initial  reporter  believed 

the  patient  was  at  immediate  risk  of  death  from  the  event  as 

it occurred; 

Congenital  anomaly; 

Cancer; 

Overdose. 
STUDY  - Systematic  collection  of  ADE's  resulting  from  a  protocol 
designed  specifically  to  investigate  drug(s)  and  adverse 
event(s). 
SUSPECT  DRUG  - Drug  associated  with  the  ADE  as  determined  by  the 
initial  reporter,  regardless  of  the  opinion  of  the  applicant. 
20  APPENDIX  B 

HOW  TO  COMPLETE  FORM  FDA  1639 

In  addition  to  the  specific  instructions  on  the  back  of  Form  FDA 
1639,  the  following  may  be  helpful: 
Item  1--For  children  under  5  years  of  age,  date  of  birth  should 
be  indicated  in  Item  1. 
Item  2--For  a  child  less  than  5  years  of  age,  the  age  can  be 
stated  in  months,  e.g.,  "18  months."  However,  make  certain  that 
the  words  "days,"  "weeks,"  or  "months"  are  legibly written. 
Items  4-6--For  congenital  anomalies,  the  date  of  birth  or  the 
date  pregnancy  is  terminated  should  be  used  for  the  reaction 
date. 
Item  7--The  reaction  should  be  described  in  detail  using  the 
reporter's  own  words.  All  relevant  clinical  information  about 
the  reaction  should  be  summarized  (signs,  symptoms,  diagnoses, 
clinical course,  etc.).  An  additional  sheet  may  be  attached. 
If  serious,  explain  why. 
Specify  if reaction  is  life-th~eatening,  cancer,  overdose~ 

congenital  anomaly,  or  resulted  in  severe  or  permanent 

disability. 

Use  initial  reporter's  own  words;  FDA  COSTART  or  other 

coding  may  also  be  added. 

Items  8-12--The  box  for  hospitalization  should  be  checked  only  if 
the  adverse  event  resulted  in  hospitalization  or  prolonged  the 
hospitalization.  For  other  hospitalized  patients  (i.e.,  those 
whose  length  of  stay  was  not  increased  by  the  ADE),  the 
hospitalization  box  should  be  left blank. 
Item  13--Include  available  relevant  baseline  laboratory  data 
(prior  to drug  administration)  and  all  laboratory data  used  in 
diagnosing  the  reaction.  This  section  should  also  include  any 
available  drug  levels. 
Item  14--Include  the  product  the  initial  reporter  suspected 
caused  the  adverse  event  (regardless  of  the  applicant's  opinion 
about  causality). 
The  report  should  be  filed  to  the  first  approved  NDA  if a 

product  has  several  NDA's  and  the  specific  one  cannot  be 

determined. 

21 
 APPENDIX  B--CONTINUED 

If  the  report  lists  two  products  by  the  same  applicant  as 
suspect,  the  report  should  be  filed  to  the  most  suspect  product 
as  determined  by  the  initial  reporter.  If  they  are  equally 
ranked,  the  report  should  be  filed  to  the  drug  that  is  first 
alphabetically. 
Use  trade  name  as  marketed  in  the  United  States,  if known. 
If  unknown,  use  the  generic  name  and  manufacturer  or  distributor. 
For  foreign  reports,  use  the  foreign  trade  name,  generic 
name  as  used  in  the  United  States,  and  include  "similar  to NDA 
II 
Item  15--The  daily  dose  should  be  clearly  expressed.  For 
pediatric  patients,  body  weight  should  always  be  included. 
For  reports  involving  overdose,  the  amount  of  drug  ingested 
as  an  overdose  should  be  listed,  not  the  usual  dose. 
Section  IV.  Only  for  Reports  Submitted  by  Manufacturer 
For  manufacturer  reports,  each  of  the  items  in  this  section 
must  be  completed  for  the  report  to  be  in  compliance  with  21  CFR 
310.305  and  21  CFR  314.80. 
Item  24c--Use  date  applicant  first  became  aware  of  the  adverse 
event.  For  followup  reports,  use  date  followup  information  was 
received. 
Item  24d--A  report  may  be  received  from  any  of  several  sources, 
and  each  applicable  source  should  be  checked. 
A  report  may  be  received  from  any  of  the  following: 
(1)  Health  professional. 
(2)  Postmarketing,  clinical  trial,  or  surveillance study. 
(3)  Scientific  literature  and  unpublished  manuscripts. 
A  copy  of  the  article or  manuscript  must  be  included. 
Foreign  language  articles  should  be  translated. 
A  separate  Form  FDA  1639  must  be  completed  for  each 
identifiable  patient. 
(4)  Foreign  sources  include  foreign  governments,  foreign 
affiliates  of  the  application  holder,  foreign  licensors  and 
licensees,  etc.  The  country  of  origin  should  be  included. 
22 
 I 
APPENDIX  B--CONTINUED 
(5)  Consumer  (including  attorneys). 
Generally,  additional  information  should  be  sought  from  the 
treating  health  care  provider.  A determined  effort  should  be 
made  to  obtain  additional  detailed  information  from  health 
professionals  for  all  serious  reactions  initially reported  by 
consumers.  When  this  additional  information  is  obtained,. Item 
24d  should  be  checked  "health  professional"  rather  than 
"consumer." 
Item  25--Fifteen-day  reports  should  be  clearly  identified by 
checking  the  "yes"  block.  (For  periodic  reports,  the  "no"  block 
should  be  checked.) 
Item  25a--Initial  and  followup  reports  should  be  clearly 
identified  by  checking  the  appropriate  block. 
Item  26a--Reports  that  originate  from  the  Centers  for  Disease 
Control  (CDC)  surveillance  systems  should  be  entered  as  "CDC"  in 
Item  26a  and  "health  professional"  in  Item  24d. 
Attachments 
Attachments  may  include: 
Copies  of  hospital  discharge  summaries,  autopsy/biopsy 

reports,  or  relevant  office  visit notes. 

summaries  of  relevant  laboratory  tests  and  other  diagnostic 
procedures,  particularly  pre- and  post-drug  values. 
In  general,  attachments  should  not  include: 
Lengthy  legal  records. 
Complete  medical  records. 
Each  page  of  the  attachment  must  have  the  applicant's  unique 

internal  control  number  for  that  case  (Item  24b). 

23  APPENDIX  C 

SAMPLE 

FIFTEEN-DAY  NARRATIVE  INCREASED  FREQUENCY  REPORT 

OF  SERIOUS,  LABELED  EVENTS 
PRODUCT: 
 (Brand  name  and  nonproprietary  name) 
MANUFACTURER  AND  NDA: 
 (Name  and  number) 
ADVERSE  EVENT(S): 
 {Describe  event;  list COSTART  term) 
DATE  INCREASED 
 (Date) 
FREQUENCY  RECOGNIZED: 

SUBMISSION  DATE: 
 (For  this  report) 
REPORT  INTERVAL: 
 {Dates  of  marketing  period  during  which 
increased  frequency  is  detected.  Note 
that  these  intervals  are  determined 
differently  for  drugs  during  the  first  3 
years  of  marketing  and  for  older drugs.) 
For  drugs  marketed  3  years  or  less, 
During  the  first  3  years  of 
marketing,  the  usual  report 
interval  is  a  quarter  (3  months). 
Drugs  marketed  longer  than  3  years, 
the  usual  report  interval  is  a 
year. 
COMPARISON  INTERVAL: 
 {Dates  of  marketing  period  used  for 
comparison.  Note  that  these  intervals 
are  determined  differently  for  drugs 
during  the  first  3  years  of  marketing 
and  for  older drugs.) 
For  drugs  marketed  3  years  or  less, 
dates  for  interval  from  initial 
marketing  to  end  of  quarter  before 
"report  interval." 
Drugs  marketed  lonqer  than  3  years, 
dates  for  year  preceding  "report 
interval." 
24 
 APPENDIX  C--CONTINUED 
ADVERSE  EVENTS  (Numbers  of  events  by  type  of  event  or 
REPORTED  COSTART  term.  For  events  in  "report 
interval,"  attach  copies  of  Form  FDA  1639 
clearly  labeled  DUPLICATE  FOR  INCREASED 
FREQUENCY  REPORT.  For  events  in  comparison 
interval,  attach  list of  manufacturer  control 
numbers.) 
DRUG  USE  (Estimated  prescriptions,  sales,  volume,  or 
ESTIMATES  other  appropriate  measure.) 
EVENT  RATES:  (Number  of  events  during  report  interval 
divided  by  drug  use  for  report  interval; 
number  of  events  during  comparison  interval 
divided  by  drug  use  for  comparison  interval.) 
INTERPRETATION  This  section  should  present  the  applicant's 
OF  DATA  interpretation  of  the  increased  frequency, 
including  possible  explanations  for  the 
increased  frequency.  The  applicant  should 
make  a  judgment  about  the  meaning  of  the 
signal.  This  should  include  an  assessment  of 
the  plausibility of  the  increased  frequency, 
changes  in  reporting  rates,  changes  in  the 
patient population  receiving  the  drug  (age, 
sex,  race,  concomitant  drugs,  other  relevant 
medical  history),  etc. 
Inclusion  of  cases  in  "report"  and 
"comparison"  intervals  is  based  upon  the 
dates  reports  were  received  by  the  applicant. 
Oates  for  drug  use  may  not  correspond  exactly 
to dates  for  "report"  and  "comparison" 
intervals  because  of  limitations  of  available 
data. 
25 
 APPENDIX  C--CONTINUED 
DETERMINATION  OF  REPORT  INTERVAL  FOR 

NARRATIVE  INCREASED  FREQUENCY  REPORTS 

The  report  interval  is  determined  differently  for  drugs  marketed 
3  years  or  less  than  for  older  drugs.  Determination  of  these 
report  intervals  follows: 
Drugs  Marketed  3  years  or  Less 
For  drugs  marketed  3  years  or  less,  ''increased  frequency"  can  be 
determined  by  comparing  the  number  of  reports  for  the  most  recent 
quarter  of  marketing  (the  "report  interval")  to  the  number  of 
reports  for  the  interval  from  initial marketing  until  the  close 
of  the  quarter  preceding  the  most  recent  one.  The  numbers  of 
reports  for  the  "report  interval"  and  the  "comparison  interval" 
are  first adjusted  for  drug  use  by  dividing  the  number  of  reports 
in  each  interval  by  the  estimated  drug  use  for  that  interval. 
For  Drugs  Marketed  Longer  Than  3  Years 
For  drugs  marketed  longer  than  3  years,  ''increased  frequency"  can 
be  determined  by  the  number  of  reports  for  the  most 
compa~ing 
recent  year  of  marketing  ("report  interval")  to  the  number  of 
reports  for  the  preceding  year  ("comparison  interval").  The 
numbers  of  reports  for  the  "report  interval"  and  the  "comparison 
interval"  are  first  adjusted  for  drug  use  by  dividing  the number 
of  reports  in  each  interval  by  the  estimated  drug  use  for  that 
interval. 
Reporting  of  Increased  Freguency 
An  "increased  frequency"  exists  if  the  adjusted  reporting  for  the 
"report  interval''  is  at  least  two  times  greater  than  the  adjusted 
reporting  for  the  "comparison  interval.''  An  exception  is  that  no 
increased  frequency  report  is  required  if  the  number  of  reports 
received  during  the  "report  interval''  is  less  than  four. 
26 
 APPENDIX  C--CONTINUED 

IDENTIFYING  AND  REPORTING  AN  INCREASED  FREQUENCY 
An  increased  frequency  can  be  determined  using  a  formula  (coupled 
with  a  table).  Using  the  formula  below,  an  increased  frequency 
exists  if  the  number  of  reports  of  adverse  drug  experiences  that 
are  both  serious  and  expected  for  the  "report  interval"  is 
greater  than  or  equal  to  the  critical  number  of  reports  C  which 
is determined  from  the  numbers  of  reports  for  the  two  report 
intervals  and  the  estimated  drug  use  for  the  two  intervals  using 
the  following  formula: 
c  =  (R  *  XC)  +  (1. 64 5  *  v 
Where 	 Xc  is  the  number  of  reports  for  the  "comparison  interval" 
~ is  the  number  of  reports  for  the  "report  interval" 
R  is  the  marketing  ratio  of  the  "report  interval"  to  the 
"comparison  interval" 
*  multiplication  sign 
The  marketing  ratio  is  defined  as 
Estimated  drug  use  (e.g.,  number  of  prescriptions, 
unit  volumes,  sales,  etc.)  for  the  "report  intervaln 
= 
R 
Estimated  drug  use  (same  units  and  scope  as  in  the 
numerator)  for  the  "comparison  interval" 
Note,  additionally,  that  there  must  be  at  least  four  reports  in 
the  "report  interval''  for  the  increased  frequency  to  be 
submittable. 
A  reference  table  (Table  C.l)  for  the  reporting  of  no  more  than 
10  ADE's  for  the  "comparison  interval''  is  attached  for  routine 
decisionmaking. 
To  use  the  table,  one  should  first  calculate  the  marketing  ratio. 
Second,  one  should  determine  the  number  of  reports  for  the 
"comparison  interval."  One  can  then  readily  identify  the  number 
of  reports  for  the  "report  interval"  that  are  necessary  to 
identify  an  increased  frequency.  The  minimum  number  of  reports 
necessary  for  an  increased  frequency  is  thus  the  intersection  of 
the  marketing  ratio  and  comparison  interval  (the  x  and  y  axes  of 
the  table). 
27 
 --
Table  C.1.  Increased  Frequency  Identification 
Minimum  Numbers  of  Reports  for  the  "Report  Interval" 
which  Constitute  Increased  Frequency  for  Given  Numbers  of  Reports 
for  "Comparison  Interval"  Adjusting  for  Marketing  Ratios 
Row  #  Marketing  Nu~ber of  Reports  for  the  "Comparison  Interval" 
Ratio*  0  1  2  3  4  5  6  7  8  9  10 
1  0.25  1  2  3  3**  4  4  5  5  5  6  6 
2  0.50  2  3  4  5  6  7  8  9  9  11  12 
3  0.75  3  4  6  7  8  10  11  12  13  14  15 
4  1.00  3  6  7  9  11  12  14  15  17  18  19 
5  1.25  4  7  9  11  13  15  17  18  20  21  24 
6  1. so  5  8  10  l3  15  17  20  22  24  26  28 
7  1. 75  5  9  12  15  17  20  23  25  27  30  32 
8  2.00  6  10  14  17  20  23  25  28  31  34  36 
9  2.25  7  11  12  19  22  25  28  31  34  37  40 
10  2.50  7  12  17  20  24  28  31  35  38  41  45 
11  2.75  8  13  18  22  26  30  34  38  42  45  49 
12  3.00  9  15  20  24  29  33  37  41  45  49  53 
13  3.50  10  17  23  28  33  38  43  48  52  57  61 
14  4.00  11  19  26  32  38  46  49  54  59  65  70 
15  4.50  13  21  29  36  42  48  55  61  67  72  78 
16  5.00  14  24  32  39  47  54  60  67  74  80  87 
17  5.50  15  26  35  43  51  59  66  74  81  88  95 
18  6.00  17  27  38  47  55  64  72  80  88  96  103 
19  6.50  18  30  41  51  60  69  78  86  95  103  112 
20  7.00  19  32  44  54  64  74  84  93  102  111  120 
*Estimated drug  use  (e.g.,  prescriptions,  volumes,  sales)  for  the  "report  interval" 
Estimated drug  use  (same  units  and  scope)  for  the  "comparison  interval" 
**  No  reporting  is required ~hen the  number  of  reports  in  the  "Report  Interval" 
is  less  than  4. 
28  APPENDIX~ 
SAMPLE  OF  TRANSMITTAL  LETTER  FOR  PERIODIC  REPORT 
DATE 
Food  and  Drug  Administration 
Central  Document  Room 
Park  Building,  Room  214 
12420  Parklawn  Drive 
Rockville,  MD  20852 
Dear  Sir or  Madam: 
Pursuant  to  21  CFR  314.80,  enclosed  is  the  periodic ADE  report 
for  (drug  product  name) . 
NDA  99999  (NDA  or  ANDA  number) 
The  time  period  covered  by  this  report  is June  1,  1990,  to August 
31,  1990. 
There  are  197  initial  Form  FDA  1639's  and  5  followup  Form  FDA 
1639's  in  this  report. 
Sincerely, 
Jane  P.  Doe,  Director 
Drug  Product  Regulatory  Affairs 
Pharmaceuticals,  Inc. 
Happiness,  New  York 
29  --
APPENDIX  E 
REPORT  CHECKLIST 
Before  mailing  your  reports  to  FDA,  the  following  should  be 
reviewed: 
A.  For  All  Form  FDA-1639  Reports 
1. 	 Have  you  completed  a  separate  Form  FDA  1639  for 
each  patient? 
2. 	 Have  you  included  your  firm's  internal 

recordkeeping  number  in  Item  24b? 

3. 	 Have  you  clearly  marked  the  report  "Periodic"  or 
"15-Day"  as  appropriate  in  Item  25? 
4. 	 Have  you  clearly marked  the  report  "Initial"  or 
"Followup"  as  appropriate  in  Item  25a?  Do  not 
package  and  send  a  15-day  followup  report  with  a 
periodic  followup  report. 
5. 	 Have  you  included  the  name,  address,  and  telephone 
number  of  the  initial  reporter  in  Items  26-26b? 
6. 	 Have  you  eliminated  unnecessary  attachments?  All 
information  should  be  submitted  on  Form  FDA-1639. 
Attachments  should  be  included,  only when  relevant, 
for  15-day  reports. 
7. 	 If  two  or  more  products  produced  by  your  firm  were 
suspected  by  the  initial  reporter: 
(a) 	 Have  you  completed  only  one  Form  FDA-1639? 
(Do  not  prepare  more  than  one  Form  FDA-1639 
even  if more  than  one  of  the  suspect  products 
was  produced  by  your  company.) 
(b) 	 Have  you  identified  all  the  suspect  products 
in  Item  14? 
(c) 	 Have  you  indicated  on  Form  FDA-1639  the  drug 
considered  most  suspect  by  the  initial 
reporter  and  directed  the  report  accordingly? 
(If  the  initial  reporter  ranked  them  equally, 
submit  Form  FDA-1639  to  the  file  of  the  first 
30  ~APPENDIX E--CONTINUED 
suspect 	 product  in  alphabetical  order.  List 
the  reaction  in  the  narrative  summary  of  the 
periodic  report  of  the  other  suspected 
product(s) .) 
a. 	 Have  you  completed  a  Form  FDA-1639  for  another 
applicant's drug?  (If  you  did,  send  it to  the 
applicant  holder  of  the  suspect drug  and  not  to 
FDA.) 
B.  For  15-Day  Reports 
1. 	 Have  you  clearly marked  Form  FDA-1639  "15-Day 
Report"  in  Item  25? 
2. 	 Have  you  packaged  the  15-day  report  (Form  FDA-1639 
or  narrative,  initial,  or  followup)  separately? 
(Do  not  package  and  send  a  15-day  report with  a 
periodic  report.  Do  not  submit  copies  of  15-day 
reports  with  a  periodic  report.) 
3. 	 Have  you  submitted  the  report  in duplicate?  (An 
exception:  for  drugs  without  approved  NDA's, 
ANDA's,  or  antibiotic  only  a  single 
applica~ions, 
copy  should  be  sent.) 
4. 	 Have  you  clearly marked  the  outside mailing 
envelope  "15-Day  Alert  Report?" 
C.  For  Periodic  Reports 
1. 	 Have  you  included  the  four  types  of  information 
required  in  the  periodic  report  (including  a  copy 
of  the  current  product  labeling)  and  have  you 
clearly separated  the  four  sections  by  marked  tabs? 
2. 	 Have  you  and  attached  a  transmittal 
complet~d 
letter to  each  duplicate  copy  of  the  periodic 
report? 
3. 	 Have  you  submitted  the  report  in  duplicate? 
4. 	 Have  you  eliminated  all unnecessary  attachments  to 
Form  FDA  1639's  submitted  with  the  periodic  report? 
Jl  _:APPENDIX  E--CONTINUED 
D.  For  Followup  Reports 
l.  Have  you  included  your  firm's  internal 
recordkeeping  number  in  Item  24b?  {Note:  this 
number  must  be  identical  to  the  manufacturer 
control  number  on  the  initial  report. 
2.  Have  you  marked  Form  FDA-1639  "Followup"  in  Item 
25a? 
3.  For  drugs  with  an  approved  application,  have  you 
submitted  the  report  in duplicate? 
32  Thursday  . 
June 3, 1993 
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Health a  nd- H.:unlaF\ 

serv'ices  '  ~.!:).:. .
-Food ancl Dl'1,1g :Administration .  .: . 
.F orm for Reporting SerioJs-Advers~; 
Events and Product Problems With    
Humaa'l  Drug and Biological Products and 
.  Devices; Availability;  Notice   
.  'i. 
/. 
t;. 
:-:  31.596  Federal Register I  Vol.-58, No.  105 I Thlll'Sclay, June 3,  1993 I  Notices 
DEPARTMENT OF HEALTH AND  Food and Drug Administration, 1401  events anq product problems. Currently, 
HUMAN SEFJVICES  Rockville Pike, Rockville, MD 20852--"  FDA relies, for the most part, on 
1448; or Division of Small  manufacturers, distributors, and user 
Food and Drug Administration  Manufacturers Assistance (HFZ-220),  facilities (hospitals, ambulatory surgical 
Center for Devices and Radiological  facilities, nursing homes, or outpatient 
[Docket No. 93N-0072] 
Health, 5600 Fishers Lane; Rockville,  treatment facilities) for reports of 
Form for Reporting Serious Adverse  MD 20857. Bulk copies of both version  adverse events and product problems. 
3500 and version 3500A may be  These parties usually obtain such 
Events and ProdUt:t Problems With 
obtained by writing to the Consolidated  information from health professionals. 
Human Drug and Biological Products 
Forms and Publications Distribution  Adverse event reporting by health 
and Devices; Avallabllrty 
Center, Washington Commerce Center,.  professionals is an efficient means for 
AGENCY: Food and Drug Administration,  3222 Hubbard Rd., Landover, MD  monitoring the safety of marketed drug 
HHS.  20785. The guideline for postmarketing  products and medical devices. 
: AcnON: Notice.  reporting ofadverse drug experiences is  Health professionals should use FDA 
available from the CDER,_Executive  version 3500 to report adverse events or 
suMMARY: The Food and Drug  Secretariat Staff (HFD-8), Center for  product problems to manufacturt)rs or to 
Administration (FDA) is announcing the  Drug Evaluation and Research, 7500  FDA. FDA encourages health 
- availability of a new form for reporting  Standish Pl., Rockville, MD 20855.  professionals to use version 3500 if they 
adverse events andproduq problems  FOR FURTHER INFORMAnON CONTACT  ;  suspect that a drug or biological  . 
-with hqman ~gprml:ucts, .biolog!c  .  -Dianne L. Kennedy, Office of the-   product, medical device,-or other FDA
p~odu~, m~~cal devt?es (m~~dmg m  Commissioner (HF-2); Food and Drug  regulated product may have been 
vttro dtagnostics), spec1al nutritional  Administration 5600 Fishers .Lane  associated with a serious outcome, such 
produ~ (dietary supplements, medical  Rockville, MD 2o857~ 301-443-01i7.  as death, a life,threatening condition, 
foods, mfantformulas), and other  , initial or prolonged hospitalization,  . 
products regula~ed by FDA. There are  SUPPLEMENTARY INFORMAnON:  disability. congenital anomaly, or inay 
two versions of the form. One version of  L Background  .  have resulted in a condition that-
the.forin (FDA Form 3500) is available -- required surgical or medical   
In-the Federal Regist~r of February_  , 
for use by health professionalsJor   intervention to prevent permanent 
26, 1993 (58 FR 11768), FDA announced 
voluntary reporting; the other version of  impairment or damage. FDA also 
the availability of two proposed 
:the form (FDA Form 3500A) istobe  encourages health professionals to 
versions ofa form for reporting adverse 
used by user facilities, distributors: lind '  report product quality problems such. as 
 events and product problems with  
manufacturers for reporting that is  defective devices, inaccurate or  . -
human drug products, medical devices; 
required by statute or FDA regulations.  unreadable product labeling, packaging , 
and other FDA-regulated products  ' 
The new form will simplify and  or product mix-up, contamination or  
excluding vaccines. The draft form 
consolidate the reporting ofadverse  stability problems, and particulate 
requested information concerning the 
events and product problems and will  matter in injectable products.   
patient, the adverse event or product 
enhance agency-wide consistency in the    Manufacturers, distributors, and user 
problem, the suspecthuman drug 
collection of postmarketing data. This  facilities should use FDA version 3500A 
product or medical device, and other 
notice also responds to written  to report adverse events and product 
information concerning the 
comments the agency received on  , problems to FDA as required in the 
manufacturer, user facility, or 
proposed versions of this form. Copies  .. applicable statutes and regulations.  .. 
distributor. fDA devel_oped the new 
ofboth versions of the new form-appear  The new form is intended to replace 
at the end of this document.  form to simplify and ,co~solidate the  the following adverse event and product 
mandatory reporting of adverse events 
problem reporting forms:     
DATES: Version FDA 3500 (for voluntary  and product problems for human drugs, 
FDA Form 1639 (all versions): 
reporting) is effective immediately;  biologics (excluding vaccines), and  .  Adverse,Drug and Biologic Experience 
version FDA 3500A (for mandatory 
medical devices, as well as to facilitate  Reporting;   
reporting) will-become effeCtive on  the voluntary reporting of adverse  FDA Form 3318: Drug Quality 
November 30, 1993. Manufacturers,  events for these and other FDA Reporting System;  
medical device distrib-utors, and user 
regulated products. FDA found that  FDA Form 2519f: Medical Device and 
facilities are encouraged to begin using.  there was confusion about what to  Laboratory Product Problem Reporting 
FDA 3500A now. 
report to the agency' and the existing  Program; 
ADDRESSES: Copies of version 3500 (for  patchwork ofreporting forms and  FDA test Form 3375:-Medical Device 
voluntary reporting) and/or instructions  systems sometimes made it difficult to .  Reporting;   
for completing the form may be  report problems guickly and easily.  FDA"'Form 3322:Medical Device 
obtained by calling 1-800-FDA-1088 or  The new form 1s part of    Report. 
writing MEDWA TCH, 5600 Fishers  MEDWATCH~FDA'snew Medical'  FDA is preparing a proposal to amend 
Lane, Rockville, MD 20857-9787. Ten  Products Reporting Program, whlCh is  the adverse drug experienCe reporting 
copies or less of version 3500A (for  .. intended to facilitate the reporting of  regulations to revise the definition of 
mandatory reporting) and/or a copy of  adverse events and product problems  "serious" and to require, among other 
the instructions for completing the form  for all FDA-regulated products by the  things, that version 3500A be used_ 
may be obtained from either: Division of  entire health care community  instead of Form 1639. In addition, FDA 
Epidemiology and Surveillance (HFD (manufacturers, distributors, user  is also preparing a final rule for adverse 
730), Center for Drug Evaluation and  facilities, and health professionals). The  experience reporting for licensed 
Research, Food and Drug  main focus of the MEDWATCH program  biological products, and a final rule on 
Administration, 5600 Fishers Lane,  is to inform and encourage health  medical device user facility, distributor, 
Rockville, MD 20857; Adverse  professionals (physicians, physician  and manufacturer reporting, 
Experience Branch (HFM-220), Center  assistants, pharmacists, nurses, and  certification, and registration. These 
for Biologics Evaluation and Research,  others) about reporting serious adverse  rules will providt> consistency with the  Fede~ ROgi.Ster l  Vol. 58, No.  105 I Thursday, June 3, 1993 /.Notices  31ti97 
provisions of the new form.B.iologics   relevant teSts or laboratory data and  it possible for human drugproduct and 
manufacturers and medical device  other relevant history.    biologics manufacturers.to submit all .  . 
manufacturers, distributors,and wier  C. Suspect Medication(s) (all products  necessary information on one side of the 
facilities will be required to use Form  except medical devices): Name, dose,  form. Version 3500A does not have to be 
3500A when the agency has finalized  frequency and route used, therapy dates,  submitted as a one page front-and-beck 
the respective adverse event reporting  diagnosis for use, lot number, expiration  form. If desired, the user facility, 
regulations for these entities. Drug    date, national drug code (NDC) number,  distributor, or manufacturer may submit  
manufacturers willbe required to.use  and other information.  .  their reports on two-pages. 
Form.3500A by November 30,1993.-All  D. Suspect Medical DeVice: Brand 
 The specific provisions of these 
manufacturers. medical device  name, type of device, manUfacturer 
 sections are explained in more detail In 
distributors, end user facilities,    name and address, operator of device, 
 section m. of this document. 
however, are encouraged to begin ushig  expiration date, product identificatjon 
 m. 
Form 3500A now.  number, date implanted and explanted, 
 Comments 0n the Proposed Form 

Adverse events associated with  and other information. 
  The February 26,1993, notice  .. 

vaccines should continue to be reported  E. Reporter: For version 3500, the  requested comments on the proposed  . 

on a Vaccine Adverse Event Reporting  reporter is the person who makes the  form. FDA received 79 comments f:roril 

System (VAERS) form and not on the  report; for version 3500A, the reporter is . representatives of the pharmaceutical, . 

new form.  the person who made the initial report   biotechnology, and medical device 

As statedhi the February 26, 1993,  ofthe adverse event or product problem  industries, as well as from hospitals, 

.n otice, FDA is committed to working   to the user facility;distributor, or  academic institutions, and health 

with health professionals and user  -manufacturer.  .  profession assoclati~ns. Although the  

Both versions ofthe form also request 
facilities, distributors.-and . . .  . ~  .  certain iilformation that is specific to  comments generally supported the US! 

manufacturers to identify rapidly  health professionals, user facilitieS,  of a consolidated reporting form, mannyn 
  
serious adverse eventS and product.  comments offered useful suggestions 
distributors, end manufacturers. For  revising the proposed form.    
problems. For the past year, FDA has  example, version 3soo includes "Advice 
consulted with industry and health    About Voluntary Reporting/' and- ,  A. General Comments  '  '
profeiiSional organizations representing 
describes "serious adverse events'' and 
physicians, dentists, nurses, and  1. Confidentiality 
"product problems." FDA encotirages 
pharmacists regarding the development  health professionals to report even if  Many comments Were cOncerned with 
of the new form and an education     they are not certain the product caused  the issue of patient/reporter  .. 
program. On May 4, 1993, FDAheld a .  the event or ifthey lack all the details.  confidentiality and the confidentiality  .. 
premeeting with organizations  The "Advice" also instructs health    statement on the proposed version 3500. 
representing health care professionals to  professionals to use additional blaDk  That statement read as follows:.  '. 
diSCUSB .ways in which these  pages if needed, and to use a separate  Olnfldentiality: The identity of the patient 
organizations Can work with FDA to  form for each patient. It also adviSes  is held in strictest confi~ence by the FDA. 
inform their members about FDA's  health professionals to notify the  .  The identity of ihe reporter ~ill be shared . 
MEDWATCH program. FDA is also.  responsible person in the facility where  with the manufacturer unless you request 
planning to conduct a conference with  a mtldical device adverse event  otherwise. However, the FDA will not 
organizations representing health  occurred, and provides telephone.  disclose the reporter's identityin response to 
professionals.and industry to announce  numbers by which reports may be  a request frmn the public.       
and explain,the MEDWATCH program.  submitted to FDA by FAX or modefl!,  Some comments questioned whether . 
In June 1993, FDA intends to publish  and telephone numbers to request  FDA and/or manufacturers are  .  
articles aboutthe.MEDWATCH program  additional information, to report  permitted by statute or ~lationto _ 
 in the.Journal ofth~America~ Medical  product quality problems, or to request  protect the confidentiality ofpatients 
Association and the American Journal  a VA  ERS foi'Jil to report adverse events  and/or reporters. Other comiD.erits  
ofHospital Phannacy. In addition, .the  associated with vaccines.  questioned whether FDA and/or .  
agency is planning conferences,  In version 3500A, section F asks  manufacturers would actually take steps 
exhibits, speeches, and articles to  medical device user facilities and  to ensure confidentialityif so permitted. 
mtorm nealth professionals about  distributors to provide information  Several commentsasked about State 
MEDWAT  CH. The agency is also    about themselves and the report.  regulation of confidentiality and Federal 
making available to health professionals  Section G in version 3500A requeSts  preemption. 
the "FDA Desk Guide For Adverse  information from all manufacturers  The Department of Health and Human 
Event and Product Problem Reporting."  concerning adverse event or product  Services (HHS) has a longstanding 
Health professionals may obtain a copy  problem reports. Section H in version  policy of providing strict protection to 
by calling 1-800-FDA-1088.  3500A requests information from device  the confidentiality of patient 
n.  manufacturers concerning adverse  information. This policy is based on a 
Provisions ofthe Final Form and 

events or product problem reports.  recognition of the extreme sensitivity of 
Other Reporting Information 

Sections F, G, and H appear on the  . this information and the personal harm 
Both versions of the form contain 
 reverse side of version 3500A. Ifa  that can result from the disclosure of 
identical reporting provisions for the 
 human drug or biologic product  such information found in HHS' 
following sections: 
 manufacturer is reporting an adverse  records. 
A. Patient Information: Patient  event in which no suspect medical  FDA, a component of HHS, has long 
identifier, age or date ofbirth, sex, and  device is involved, the manufacturers  shared the same belief in the importance 
weight.  section (section G) on the reverse side  of personal privacy and has  . 
B. Adverse Event or Product Problem:  of version 3500A may be completed and  implemented this confidentiality.policy 
Outcome attributed to event (e.g., death,  reproduced in placa of the suspect  in its public information regulations 
disability, etc.), date of event, date of  medical device section (section D) on  (see part 20 (21 CFR part 20)). Under the 
report, description of event or problem,  the front side of the fonn. This makes  authority of Exemption 6 of the  -~ 
31598  Federal Register I Vol.  58, No.  105 ./ Thursday, June 3, 1993 I Notices . 
.  . 
~ 
Freedom of Information Act (FOIA),  from the public, pursuant to the Freedom of  available on the FDAelectrt>nicbulletin: 

these regulations have for many years  Information Act.  board system at 1-80().;-222.;.()185 .    " 

protected patient names and other   2. Consistency With Other Forms  To explain more thoro uglily the  

identifying information from disclosure  mandatory reporting requirements for' 

in response to requests filed under the  Several comments asked how and  manufacturers, distributors; and user 

are 
FOIA.  whether the agency's efforts to issue a  facilities, CBER and CDRH  prepmng  

The agency also recognizes the  consolidated form were consistent with  specific reporting guidelinesto ,  : 

importance of protecting th~ identity of  recent initiatives on clinical safety data  accompany each Center~adverse everit. . . 

individuals who voluntarily report  m~agement by the International  reporting regulations. When. these  -.  ~: 

information to the agency, specifically  Conference on Harmonisation of  regulations become final ~dthe  '' 

including those who report adverse  Technical Requirements for Registration  guidel(nes are completed; FDA will, " 

reactions or product experiences. Thus,  of Pharmaceuticals for Human Use (ICH)  announce their availability in a future 

the regulations also protect from public  and the international reportingof drug  issue of the Federal Register.  ..  ; . 

disclosure the identity of the individual  safety by the Council for International  Concerning adverse event reporting for 

yoluntarily reporting, whether that  Organizations ofMedical Sciences  human drug products, FDA has made ' 

individual is the patient or a health  (CIOMS).  available the "Guideline for  r '  .  

professional, as well as the identity of  The agency believes the forin is  Postm(U'ketingReporting ofAdver8e  .. ~  

the. hospital or other institution    consistent with _adverse reaction reports  Drug Experiences.  These guidelines 

a~sociated with the report (see  20.111).  created or proposed by international   will be updated to be consist~nt with 

The agency has maintained its  organizations. For example, ICH is - .  the changes made in the regulations for 

protection of the identity ofvoluntary  working on a draft guideline that would  the reporting of adverse drug  ,  .:. -~"- .. 

reporters because of its belief that  consider a serious adverse event, , . _..  experiences and the new Form 3_500:A~>f:f.: 

confidentiality is a key to encouraging  experience, or reaction to be an incident  4; Space on the Form  '  '~:~; <
.health professionals to report serious    that results in death, requires inpatient 
adverse experiences. Such reporting is  hospitalization or prolongs existing  Several comments asked whafshoufdc . 

essential to the agency's postmarketing   hospitalization, results in pe~istentor  be done if more-space is needed to;/:~... 

surveillance program, which is designed  significant disability/incapacity, or is  complete the sections of the form; :.;<ii.V>/; 

to help ensure the. continued safety of  life-threatening. The companies may  FDA advises reporters to use  -  ~,,<~; 

marketed health products in the United  continue to use the CIOMS form for  additional blank sheets of paper,  : ~.:~-; 

States.  reporting foreign events with prior  referenced to the section ofthime fyo rm \}';J)-::]"'' 
 
approval.  .  -being described, to complete 
. FDA has been informed ofa number 
narrative sections of the form. 'Reporters'..,  
oflawsuits pending in State courts in  3. Development of Guidelines 
should use additional 'copies of the fotiri: 
which manufacturers have been   
requested and, in some cases, ordered to  Several comments requested  to complete all other sections. FDA 
additional information about the  l'Bminds reporters to number allextra 
provide the names of those reporting 
adverse reactions to particular products  fFoelbloruwairnyg 2 s6ta, t1e9m93en, nt omtiacdee:  i"nS ptheec ific  pages,,  and the form with "page----o. f  ,
and, rarely, the names of the patients 
involved. Because of the agency's  user facility, distributor, and  ,  Several comments stated that the 
concern about these confidentiality  manufacturer reporting guidelines Will  space permitted for the re-quested   .  .. '.'  ':? 
issues, the agency, through the    be developed to provide guidance in the  information on the form as reproduced" ' . 
use ofthe new form." The comments  in the February 26, 1993, Federal     
Department ofJustice, has filed a  
statement of interest in a number of  asked whether the guidelines being  Register was insufficient:   
these cases. The statement informed the  developed are specific to the new form  .  FDA advises that theactualsizeofthe
courts of the potential damage tlie ..  and when will they be made available.  form is.8 i/2" by 11" and that its siZe. 
agency believes would be done to its  In addition, the comments asked about  had been reduced to accommodate 
postniarketing surveillance program if  the availability ofguidelines for'the~  publication in the Federal RegiSter.  . 
the identities of patients and reporters  existing adverse event and product  Copies of two versions ofthe forni'in . 
are released to plaintiffs in these cases.  problem reporting regulations for  their actual size maybe obtained by 
The agency believes that the  human drugs, biologics, and medical  request as stated at the beginning ofthis. 
confidentiality of this infomiation has  devices.  notice.   
been maintained in all of the cases in  To explain more thoroughly the  5. Recommendations for Additional 

which it has participated. Because such  voluntary reporting program for health  Information on the Form 

cases are of continuing concern, FDA is  professionals, FDA Qas prepared the 
currently exploring ways in which it  .  "FDA Desk Guide for Adverse Event  One comment recommended that 

might further.stren~en its regulations  and Product Problem Reporting" which  reporters should be able to indicate 

to protect patient and reporter  includes the instructions for completing  ''ethnicity" on the form.  , 

confidentiality,  the voluntary Form 3500.'FDA also has  The agency notes that section B.7 on 

In orderto_emphasize some of these  prepared instructions for completing the  both versions requests "Other relevant 

precautions, the confidentiality  mandatory reporting Form 3500A. Both  history, including preexisting medical 

statement on version 3500A has been  versions of the form and their respective  conditions (e.g., allergies, race,  . 

revised to read as follows:  - instructions are available now and may  pregnancy, smoking and alCohol use, 

I  be obta~ned from the Center for Drug  hepatic/renal dysfunction, etc.)." A 

Confidentiality: The patient's identity is  Evaluation and Research (COER), the  reporter may indicate ethnic origin in . 

held in strict confidence by FDA and 
Center for Biologics Evaluation and  this section. 

protected to the fullest extent of the law. The 
Research (CBER), and the Center for.  One comment asked where on version 

reporter's identity may be shared with the 
manufacturer unless requested otherwise.  Devices and Radiological Health (CDRH)  3500 reporters should indicate whether 

However, FDA will not disclose the  (addresses identified above). Copies of  the report is an initial report or an 

reporter's identity in response to a request  both sets of instructions are also  update.   
 Federal Register I Vol. 58, No. 105 I  Thursday, June 3, 1993 I Notkea  31599 
,. 
For the initial reporter, the  pharmacists, and industry regarding the  gender. One co~entobservedthat 

information should be included in  design and content of the form. FDA  there was no place to desi_gnate that the. 

section B.S of version 3500. For user  modified the draft form in response to  gender is not known.      .  ...  ..   

. ~.I 
facilities, distributors, and    many of the suggestions made by these  FDA believes that health professionals  
manufacturers; this information should  groups. In addition, FDA has made a  will generally know the patient's  .'\ ,. 
be included in section G.7 of version  number ofrevisicms to the final form  gender, and FDA encourages whoever 
3500A.  .  based on comments made by health  has the first direct contact with the 
Several comments suggested that the  professionals and industry  patient or knowledge ofthe event to. 
disclaimer at the bottom of the front  representatives who will be using this  providiJ.as much information as  . 
side of proposed version 3500 page  form. Finally, during the initial period  possible. As with all the fields in the 
should be broadened to say:  of its use, FDA will continue to closely  report, ifinformation is not known, the 
"Submission ofa report does not  monitor comments imd suggestions it   field can be marked as unknoWn. 
constitute an admission that medical  receives from interested parties on the  Section A.4 in the proposed form 
personnel or the product eaused or   form, and will consider making further  req\lested the patient's weight in ' 
contributed to the event." One comment  modifications to clarify and simplify the  pounds or kilograms. Several comments 
suggested that the language for the  form as the need arises.   said that weight data are difficult to 
disclaimer should be the same as the  B. Section A (Versions 3500 and .  obtain and are meaningless unless 
language in803.24(f) (21 CFR  50DA}-:-Patient Inoimation  height data are also pro~ded. One 
803.24(f)), which provides more  3. ~  comment noted that there was. no place 

specifically th~ medii::al device reports  Section A.l ofthe proposed form  for pediatric body weight.    .    . 

do not in themselves constitute    requested "patient initia1s"and stated  Fl>A has decided to retain the space 

admissions ofcausality or liability.  that the initials would be "in  on the form for weight for those:'  . 

FDA has amended the form to add the  confidence." FDA.received numerous  instances-in which it can be provided. 

language "or contributed" to the ..  comments expressing concern about  Some dosages are prescribed in terms of 

disclaimer. The agency has nOt,     asking for the patient's initials. claiming  a patient's weight withoutreganHo 

however, adopted the language of  that providing a patient's initi~s would  height, and sothere may be instances 

 B03.24(f) for the form because that  compromise patient confidentiality.  where the weightis usefulby itseH..  . 

degree of sjlecificity woUld be  Some comments also noted'tliat other .  . F DA can determine from t,he age ofth8~ 
inappropriate for purposes.ofthis form.  identifiers, lruch as an identifying ..   patient whether the weigh~ispediatriC 
number in a clinical trial, might be more  weight.   
6. RepOrts from Co~smners and to 
 available and more useful.,One         
Manufacturers   
 comment suggested adding or  C. Section B (Versions 3SOO tr350QAr 
Several comments asked whether  substituting the pharmacy prescription  Adverse Event orProduct Problem   ' 
there will be a form that consumers can  number of the suspect medication as the  Section B in the proposed form was 
use to report adverse events and product  identifier.  .  titled, "Adverse event or product 
problems to FDA, or whether consUmers  FDA has modified section A.l to  problem." One comment suggested . 
should use the form for health  request a "patient identifier." The form  changing the title to "product related . 
professionals.  .  does not specify the type of identifier  event~ rather than "product related. 
Although FDA expects that moSt 
 that may be used. The reporter may use  problem." The commentasserted that. 
reportswill conie from health   
 any number or other identifier that will  health professionals might be len likely  
professiOJials; consumers are 
 allow the reporter to identify the patient  to report an adverse ev:entif the 
encouraged to work with their health  
 if contacted for followup. This change  language suggests that the product has  .. 
professionals to submit version 3500. 
 . will allow-different reporters to use the  already been determined: to be the cause . 
One comment stated that the   
 identifier they believe is most  of the problem.   .  . 
submission ofversion 3500 to FDA 
 appropriate, and willprovide additional  The agency disagrees with this 
would impede the ability of 
 protection to the patient involved.  comment. The term "product problem" 
manufacturers to take corrective action 
 Section A.2 in the proposed form  might be better understood by more 
concerning adverse events or product 
 requested the patient's "age at time of  people th~the term "event" and may 
problems.   
 event." Several comments suggested  therefore lead to more comprehensive 
FDA disagrees with the comment. The  that FDA include the date of birth in  reporting of possible problems.  . . 
agency intends to inform expeditiously  addition to, or instead of, the aga of the  Another comment suggested that the 
manufacturers of any product problem  patient. One comment asked how to  term "product problem" be reserved for 
reports it receives as well as reports of  record the.age at the time of event. when  devices only.   
~rious adverse experiences. The agency  multiple experiences are being reported,  Although the term "adverse drug 
will expedite the transmission of these  and one noted that there was no  experience" is aSsociated with the 
reports to enable manufacturers to  reference to age in hours when 1UJ.  regulations pertaining to adverse drug  . 
conduct rapid and effective followup. In  adverse event affecting a neonate is  experience reporting, the more general 
addition, the agency notes that health  being reported.  "product problem" may be applicable to 
professionals may report to FDA or the  .  FDA liaS revised the form to enable  other FDA-regulated products,  . 
manufacturer.  .  the reporter to supply the patient's date  including drugs and biological products, 
of birth or age at the time of the event.  as well as devices. A general term that 
7. Use of the Form on a Test Basis 
As for recording the age at the time of  is applicable to all classes and types of 
One comment recommended that the  the event when multiple experiences are  products is more appropriate for a single 
. form should be used on a test-basis first  being reported, the age reported should  form that is used for the reporting of 
before it is finalized~    be the age at event onset. The form does  problems associated with each ofthe 
The agency advises that in developing  not specify years or months, so hours  types of products. FDA has retained the 
the draft form, it consulted health  can be used ifa neonate is involved.  headings and terminology referring to 
professional organizations representing 
 Section A.3 in the proposed form  adverse events and product problems. 
physicians, dentists, nurses, 
 requested information on the patient's  The agimcy does not believe that the  31600  Federal Register J  Vol.  58, No.  105  I Thursday, June 3,  1993 I  Notices 
language. is misleading. The outcomes.  required intervention to prevent  FDA received one comment 

attributed to the adverse event will be  permanent impairment/damage, as  conteming the "other" listed reason for 

described and the description of the  derived from. 803.3 (21 CFR 803.3)).  reporting an adverse event. Orie  

event or problem Will clarify whether  This section is for the general reporting  comment suggested that FDA could 

the product being reported is a drug or  and description of the event. FDA does  increase the number of reports received 

a device. This will facilitate the agency's  not want to limit the choices of reasons  by broadening the "other" category to 

direction of the form to the proper  for reporting in this general section, but  include such reasons as loss of work, 

program for attention.  would rather leave the reporter all the  physician visit required, pharmacist 

Se.ctwn B.1 of the proposed form  options that might be applicable.  intervention required, product not  ~ 

asked whether the report pertained to an  Further specificity may be provided in  working properly, product defect, and 

"adverse event and/or product problem  later sections of the form.    unexpected effect.  . ' 

(defect or malfunction)." Several  In addition, the purpose of the new  The reporter may indicate the "other" 

comments supported drawing a  form is to consolidate the reporting of  category for any serious event thatdoes 

distinction between defe.ct and  adverse events and product problems  not fit into the other categories 

malfunction of medical devices-. The  for all FDA-regulated products in order  provided. The reporter may explain the 

proposed form d~d not define these  to enhance agency-wide consistency in  reason in the space provided 

t13rms, but listed them separately, i.e.,  the collection of postmarketing data.  immediately after the word "other" and 

"defects or malfunctions." However,  Several comments asked FDA to 
 in the narrative in section B.S.  . 

some comments suggested deleting the  define "disability.'~ 
 FDA received several comments 

terms "defe.ct" and "defective,".stating  As noted above, FDA is asking that  questioning the purpose of and support 

that such terms could have an impact on  only serious adverse events be reporte-d.  for reporting coT,~genital anomalies. One 

product liability action.  . .   An event is serious if it results in a  comment Sl,l&gested that it might fnvolve 

The fina,l form has replaced "l;lefect or  disability that is significant, persistent,  drawing concl~ions that could be. 

malfunction" with "defect/  or permanent, as described on the  legally damaging to a provider and  

malfunction... Defects may be related to  reverse side of version 3500.  beyond the capacity of the risk manage~ 

product design or manl,lfacture whereas  Several comments asked FDA to  in a particular hospital.  .  ...' 

malfunctions may be related to a device  explain the phrase "required  .  FDA has retained the category of;:, 
not operating as iil!ended. For purposes  intervention to prevent permanent  congenital anomalies pecause these ~ . 
of reporting, however, the agency does  damage.'' Other comments said that this  events are relevant to the evaluatioifof 
not believe these distinctioQs need to be  pertains only tQ devices and should be  the safety and efficacy of productS;'    
set out on the form itself, because the  so described.  /'.  Experience has.shown that these  .< 
,?, 
agency is not asking the reporter to  FDA has replaced "required ..  abliormalitj.es can occur through th~ru~..  ~ 
make such distinctions on the form: .  in!ervention to prevent permanent  of certain drug products. For example;  
Although the underlying information  damage" with "required intervention to  the drug thalidomide; used in Europe as 
may be relevant to product liability.  prevent permanent impairment/  .  a sedative in the 1960's, caused serious 
issues, submitting the form itself, as is  damage" to be consistent with statutory  cangenital anomalies in the fetus, 
clearly stated onthe form, doe.s not  -and regulatory language. The agency is  including dysmelia, or malfqrmation.of 
constitute an admission that the product  proposing to add this element to the  the limbs, when taken early. in 
caused the adverse event. FDA needs  regulatory definition of "serious...as that  'pregnancy. - .   
information on defects and  term is applied to adverse experiences  The form is intended to help FDA 

malfunctions to protect the public  with drugs and biologics. This proposed  identify possible serious adverSe events 

he.alth.   change makes the definition of  and product problems ~n order: to 

Section B.2 in the proposed fomi  "serious" consistent for drugs, biologics,  ptote.ct the public health. Vel'Sion  
pertained to "Reasons for reporting  and devices and also reflects the  3500A bears specific disclaimers stating 

adverse event".and listed seven reasons:  definition of "serious" proposed by the  that submission of a report does not 

"death;'1 "lila-threatening,"  -   International Conference on  constitute an admission that medical 

"hospitalization-initial or prolonged  Harmonisation of Technical  personnel, user facility, distributor, 

due to event," ~disability," "congenital  Requirements for Registration of  manufacturer, or product caused or 

anomaly,'' "required intervention to  Pharmaceuticals for Human U.se (ICH).  contributed to the event. Version 3500 

prevent perman~uit damage," and  .  The agency'believes it is' desirable,  bears a similar disclaimer that 

"other;" for reportingan adverse event.  where possible, to have a consistent   submission of a report does not 
The proposed form directed the person  definition of what constitutes a serious  constitute an admission that medical 
completing the forQI to "check,all that   adverse event for all regulated products.  personnel or the product caused or 
apply.'' FDA receivedniany comments  FDA hopes that such consistency will  contributed to the event.   
stating that some listed reasons for  eliminate confusion about what events  One comment suggested that FDA 
reporting apply only to certain classes of  should be re~orted. Further guidance  delete "Reasons for reporting adverse 
products and the categories are,  will be provided in adverse event  event," but retain "check all that apply" 
therefore, too broad, and suggested that  regulations in the near future.  because the outcomes listed are 
these specific limitations to classes of    One comment asked whether  pertinent outcomes but may not be the 
products be described in the se.ction of  treatment with a drug is an intervention.  reason the event is being reported:   
the form listing outcomes.  The agency advises that drug  To address this concern, FDA has 
FDA acknowledges that not all  treatment necessary to preclude  modified the title of this field to 
reasons listed are applicable to all  permanent impairment of a body  "Outcomes attributed to adverse event.'' 
classes of products and reporters. Some  function or permanent damage to a body  This will clarify the agency's intent that 
relate primarily to drugs (e.g., congenital  structure would constitute intervention.  pertinent outcomes thought to be 
anomalies, as included in  310.305,  Another comment sought clarification  attributable to the adverse event are the 
312.32, and 31:4.80 (21 CFR 310.305,  of the term...permanent damage."   ones that reporters should identify. 
312.32, and 314.80)), and some relate  "Permanent damage" means damage  On a related issue, one comment 
primarily to medical devices (e.g.,  that is not reversible.  stated that if the date of death were  Federal Register I  VoL 58, No. 105 I Thursday, J\me 3, 1991 I Notices  31601 
being included with the reasons for  that such information is relevant for 
 FDA agrees that it would be useful to 
'reporting adverse events, it would be  regulatory purposes. 
 include allergies in the list ofconditioris 
~portantto leave spaee to clarify  . Section B.5 of the proposed form 
 and bas revised the form accprdingly. 
a
whether the repQrted adverse event was  requested  reporter to ''describe event 
 One comment asked whether ICD-9 
the cause ofdeath. Another comment  or problem,'' and to "attach hospital 
 codes (an International Classficiati()I) of 
said that the form should indicate  discharge summary, ifavailable. One 
 Diseases code) and verbatim terms  ' 
whether "death" should be cheCked if it  commentsuggested adopting the  . 
 should be included in this section. 
is not related to the adverse event.  language from the FDAtest Form 3375 
 Including ICD-9 codes and 
 The revised form does include a space  (Medical Device Reporting) that requires  descriptors of the codes is optional for 
for the date of death, Since the reporter  a narrative description of relevant  manufacturers. 
is told that section B.2 is for "Outcomes  informati?Jl 
D. Section C (Versions 3500 and 
attributed to adverse event," ifthe  FDA believes that any information  1 
3500A)-Suspect Medication($) 
patient died while using the product,  . that is rel~vant to help FDA determine 
b u t. the  reporter d 088 not thin k th8  d 98th  bthee i ncaculusdateido nin o tfh aen . naadrvreartSivee e ivfeitn its s hnooutld Section C in the proposed form would . 
was related to the event, the reporter
 require information on "suspect  . 
should not check the box for "death" on  already provided by other sections of 
 medication(s)," such as the dose, 
the form.  the form. However, "Attach hospital 
 frequency, and route ofadministration,_ 
Sections B.3 and B.4 ofthe proposed  discharRe summary, ifavailable" has  therapy dates, diagnosis for use pr .   . 
form pertained to the "date ofevent"  been d~1eted from the fin$! form to  indication, and exp~tion date.   
and "date-of this report," respectively.  dispell the impression that the hospital  One comment preferrecl the use of . 
FDA rooeived several comments  . d._ischarge summary is required. FDA  "associated medication(s)" rather than  
suggesting that these dates are  encourages the reporter, however, to  "susp~10edication(s)," saying tha,t the 
ambiguous or unn8cessary.  attach the discharge summary if  term "suspect" implies causality that{;:_ 
theO rneep coo.r t.m  hmi seenct  t8io8kn .l; t.B.U.J.  4h  odwiff tehres   fdr ao tm e  oth f e  . apveSartielacaitbniloeedn.   tB. o. 7 olifs tt hineg p orof "pporseee dx fiostrimn g~
  
 osFteDnAsi bblays,  rheatsa innoetd b teheen u psreo voefn th._e ..J:te;n+n: '. ....:  
date the manufacturer rooeives the  medical cond8 itions and other relevant 
 suspect because the report isiniend~i:l. 
report, which is requested lil section G.  history." In the proposed fotm for user 
 to alert manufacturers and FDA to,.. ;-  
FDA b&s not changed these sections of  facilities, manufacturers, arid  suspected Unks between particular- : 
the form. FDA believes that both ofthe  distributors, this section contained four  products and adverse events. The \   
dates are necessary because they .  . lines for entering information. Several  agency does not believe that this term. 
proVide important information for both  . comments opposed the inclusion ofthe  ' "suspect" implies that causality bas :, 
identification and regulatory purposes.    d lin  been proven. In addition, the term 
To proVl' de .cl arifi cati. on ~~ or the  terms  prTephnen ptree prinates.d  lines w. ere-- .o rigi-nall.y  "associated medications" might be 
"date ofevent" and "date of this  included to allow for the option of  construed as "related" or "concomtiota n t"' 
report," the "date ofevent" fs the date  optical scanning, but the lines 8re not  medications. The form is intended 
of first onset ofthe adverse event. The  -, necessary for the technology that FDA  collect information about drug products 
"date of this report" is the date that the  currently uses and have been deleted  connected with particular adverse< 
report is filled out by the individual   from the final vei'Sions of the form. For  events and problems. The co~comitant 
!Jubmittiog the report. The dat~ the    submission of adverse events related to  medications are requested separately on 
report is filled out may pr may not differ  the use ofbiologics, optical scanDing  theform.  .  /  . 
from ~edate that .the manufactUrer .  remainS a useful tool for FDA to  Two comm~tssuggested adding.  . :1 
receives the report. The date of.the  . .  enhance the speed and accuracy of data  "manufactufer8 only" to "Suspect...~ ._,   
report in section B is not redundant  entry, and FDA urges biologics  medication(s)" because userfacilities 
with the date the manufacturer rooeives   manufacturers to submit forms that can  are not required to report medication 
the report because these two dates also  be optically scanned. The agency  problems. One comment noted thatuser. 
may differ.  .  .  recognizes that for the successful  facilities who choose to report  .   _ 
One comment said that section B  application ofoptical scanning 
 medication probleniS C8Il use version  
should include an entry for the date of  technology, replication ofversion 
 3500.  . .  
completion of an investigation of an  3500A will require a high level of 
 Not all elements of version 3SOOA are 
edverse event so that FDA can verify  precision. Manufacturers will be  . 
 required by regulation for each type of- 
that the report has been submitted  required to submit their computer-
 reporter. The agency believes that  . 
within 10 days ofthe investigation.  generated version of the form for 
 asking user facilities to report ontwo 
Another comment stated that a date  approval by the agency. 
 different versions of the form would be 
indicating the date it is determined that  One commentindicated that  confusing and will not facilitate the  -
an event is reportable should be added.  preexisting medical conditloQS are pert  ability of~ user facility ~o receive a  _ 
FDA does not believe that it needs  ofthe confidential medical record and  report from a health profassional and 
information in. this section that  should not be required on either version  relay it to FDA. In addition, FDA wants 
describes the length of the investigation,  of the form.  to know about suspect drug products 
the date the reporter determines that an  The knowledge of preexisting medical  that may have contributed to an adverse 
event is-reportable, or. the date of  conditions is often crucial to an  event associated with a medical device. 
completion ofthe investigation.  adequate evaluation of an event. Ifa  Section C.l of the proposed fol'J)l  . 
Pursuant to revisions in section F.6 that  confidential patient identifier is used, it  requested information on the "Name & 
are described more fully below, the  is not likely that simply indicating a  strength (give mfr/labeler ifknown)" for 
revised form will now provide  patient's medical history would identify  the "Suspect medication(s}." The  
information from which FDA can  the patient.  .  proposed form provided lines for two 
determine the lengths ofinvestigations  One comment suggested including  separate suspect medications and   
 or the date that a reporter determines  allergies in the list of preexisting  designated them 88 "a" and "b. "-8everal 
that an event is reportable, to the extent  medical conditions.  comments suggested replacing the  3160Z  Federal Register I Vol. 58, No.  105 I  Thursday, June. 3, 1993 l  NotiCfS. 
letters "a" and "b" with numbers ("1"  provide sufficient information to  Section C.9 in the ~r~posed frirm .. 
and "2").   evaluate the relationship between the  requested the suspect medi~t!oh(s),';. 
FDA has revised the form as suggested  suspect medication and the adverse  NDC number, ifknpwn. FDA'received 
by the comments.  event. The comments suggested that  several comments stating that. the NDc 
One comment suggested removing the  FDA revise the section to indicate the  number is often not available arid.is 'of 
preprinted lines to facilitate more  temporal relationship between the  little value.  .  .  ... . ~ 
efficient use of available space by  starting and stopping date~ of the  FDA has revised the formJo specifY' 
computer systems.  .  .  '  administration. ofthe drug and the onset  providing the NDC number when:  . 
The final form retains one line for 
 of the adverse event.  reporting "product probl~nis only{if c 
each of two possible listed suspect 
 FDA agrees that, when available,  known)." Knowledge of the NDC ,  ' 
medications. FDA believes that 
 starting and stopping dates of drug  number is critical when evaluating a  
providing the lines will make the. 
 therapy are very important pieces of  .  reported drug quality problem;.>.,  . 
submission of information clearer and 
 information. However, when these dat'es  However, if the .reporter does not kno\V ' 
easier to read. 
 are not known, it is preferable to have  the NDC number, it can be omitted. s.,.' 
Regarding the section requesting the  information on duration of therapy thlin  Section C.10 _in the propo5ed,forin::  
name and strength of suspect  to have no timing information at alL The  required information nn "other :.  
medications, one comment said that  agency, therefore, declines to revise this  medications/devices used prio,to  _ 
drugs are not addressed in the tentative  section except tp encourage the reporter   event" and "therapy dates,'' The form.  .. 
final rule entitled Medical Devices;  to estimate the dates and duration if  also corifained three lines, marked''a,'' 
Medical Device, User Facility,  exact dates are fiot known.  "b," and "c" for listing information~ 
Distributor, and Manufacturer  Section C;4 in the proposed form  Several comments said that this  '.,' .   . 
Reporting, certification, and     concerned the "Diagnosis foruse  language was misleading and suggf;!,sted 
Registration published in the Yederal  (indication)." FDA received one  that "concomitant medical p.roou,~.~:l" 
Register of November 26, 1991 (56 FR  comment suggesting that the words "if . :  w.ould more clearly indic:ate th{ltthe::.  
60024) and are not subject to the niles  known" should be added to the heading  information sought pertains to p~duqts 
applicable to medical device reporting.  of "Diagnosis for use (indication)"  used immediately pripr to ,or at the .mime 
As noted earlier, thereporting form .. is  because community pharmacists may   time that the event occurre~:,.Spme ;<>. 
not for dfi!vices only. FDA regulation!i at  not know'the underlying diagnosis for a   comments asked that the preprin!!l~.'   
 310.305~ 312.32, and 314.80 require  preScription.    lines be deleted.   :,  ' /h"i'>
 adverse event or safety reports for   FDA declines to accept the  :FDA agrees that the \YOrd  ,  :;_.;;~  . 
human drug products. CBER is ~so  suggestion. In most cases, FDA expects  "concomitant" provid~s a cle,arer.;,:'!V;f, 
preparing final regulations that adopt  that the reporter will know the    description oftheinforination sough!~~.' 
similar reporting requirements for  diagnosis for use because the reporter  and has revised the form accordingly:::. 
biologics. Adverse experience  either will be the physician who made  The agency pas also removed the ;r  y 
information is used to further FDA's  the diagnosis or the manufacturer who  preprinted lines from the form to ' .,  ~2: 
objectives ofeffectively monitoring the  can obtain the information from the  provide more flexibility.in entering  
safety and efficacy of human drug and  initial reporter. The reporter may also .  information.  '  . :~-
biological products.    state on the form that the diagnosis is  One comment suggested that this  
Section C.2 of the proposed form  unknown if the information i8.llot  section and its counterpartin D.lO, 
requested information on the "dose,  available.    .  ".other medications/device-s used prior 
c.s 
frequency 8t route" for the suspect  Section  i1,1 the proposed form   to event," be combinedarinmoved to 
medication(s}. One comment suggested  asked whether the adverse event  section B (Adverse event or prodUct 
that these items pertainto the drug  "abated after use stopped or dose     problem).  ,..  < .   
product "as used" rather than "as    reduced;" The form contained "yes/no"  The agency. declines to ~ake tliis 
labeled."    boxes for two products, designated as   change. FDA wants to separat!J th!! 
Although the proposeg form did not  "a" and "b." Several comments  specific data concerning dJv,gs or ; 
specify either "as used" or "as labeled/'  suggested that a space be added for "not  devices so.that each may l.lead<Jressed 
FDA has adopted the suggestion.  applicable" for drugs, such as insulin,  separately. Section B of the foi:m is for 
Consequently, section C.2 of the final  that are generally not discontinued after  describing the adverse e~ent itself; . 
form pertains to the suspect .  .  .  an adverse event, or "unkno\vn," for    while sections C.10 and D.10 
medication's dose, frequency, and route  cases in which the information is not  respectively requeSt a deScription of  . 
"used."   
 available. FDA received several similar  : concomitant medical products ln use at 
One comment suggested that 
 comments for section C.8 in the  the time of the adverse event butnot 
. providing total daily dose would be 
 proposed form, which asked whether  used to treat the everit. FDA believes 
clearer than providing the dose, 
 the event reappeared 'after    that reporting the information in. this 
frequency, and route as prescribed. 
 reintroduction ofthe drug product.  . way willbe clearer and less likely to 
FDA believes thattotal daily dose will  In each instance; FDA has added a  cause confusion. 
not provide important information  box to check for "doesn't apply" but, 
about dosing intervals and dosage  because of space limitations, has  E. Section D (Versions.3500 and 

35DOA)-Suspect Medical Device , 

strength that might distinguish between  declined to add an entry for 
. multiple preparations of the same  "unknown." Generally, FD~expects  Section D of the proposed form, 
chemical substance. In addition, total  that the reporter will know whether the  "Suspect medical device," requested 10 
daily dose can be calculated from dose  event abated after reduction or  items of information: (1) The product. 
and frequency.  elimination of the drug treatment and  name of the device; (2) the type.of  . 
Section C.3 of the proposed form 
 whether it reappeared after  device; (3) the device manufacturer's  
pertained to "Therapy dates (or give 
 reintroduction. The field may be left  name and address; (4) whether the 
duration}."   
 blank or "unknown" may be written in  person operating the device was a 
Several comments expressed concern  ifthe information requested is not  health professional, lay user/patient, or 
that duration'oftlferapy does not  available.    "assistive personnel;" (5) the expiration  Federal Register I  Vol. 58, No. 105 I  Thursday, June' 3, 1993 I  Notices  31603 
date of the device (ifhown); (6)  whether this referred to the  manufacturer generally reduces the 
information specifically identifying the  manufacturing site or the reporting site.  manufacturer's ability to identify the  
device, such as the model, catalog,  FDA advises that the name and  cause of the problem. It may not be 
serial, lot, or other number; (7) if  address refers to the reporting or  practicable, however, to return all 
implanted, the dateofimplantation; (8)  headquarters site. The agency urges  devices as, for example, when a patient 
if removed, the date of removal; (9)  voluntary reporters to provide whatever  who owns a device will notrelinquish 
whether the device had been returned  information is available to them  it or where shipping the device might 
and was available for evaluation; and  regarding the manufacturer. In the final  pose possible public health problems.  .. 
(10) other medications or devices used  form, section G.l, mandatory for all  The agency, on its own initiative, has . 
a
prior to the event and the therapy dates.  manufacturers. now specifies that the  amende section 0.9 of the form to state : 
FDA received a number of general  name and address for the contact office .  that the suspect medical device should 
comments on this section. Several  and the site of manufacturing for a .  not be sent to FDA. The agency has 
comments proposed reversing the  device be provided.  made this change because  . 
locations of Sections G ("All  Section D.4 of the proposed form  manufactUi'ers, not the agency, have the 
manufacturers"Lando so that all  asked whether a health professional, lay  primary responsibility for performing an .. 
information regarding suspect  person, patient. or "assistive personnel"  evaluation of the device and are best 
medications could be presented on one  operated the suspect medical device.  equipped to provide instructions.on the 
side ofthe MEDWATCH form.  Several co_mments questioned the term  shipping imd handling ofa device.  . ,. 
As stated above and in the February   "assistive personnel," noting that health  One comment asked FDA to i11clude.  . 
26, 1993, notice, ifa medication    professionals rarely use this term.   a sp.a ce. ." for the current possessor ofth-e 
manufacturer Is reporting an adverse  FDA agrees with these comments and  devJce.  .  .  . 
edvevenicte i nis w inhvicohlv neod ,s tuhsep mecatn mufeadcitcuarle rs  hdaessi rgenpaltaicoend w thheic the rcman w bieth u asend " boyth er"  suFgDgeAst edde cblyin tehse t coo ammmeenndL t hFeD.fAor nmo atess  
section (section G) on the reverse side .  individuals,,s'uch as nurse's aides,  that the form, at section 0.9; aSks.  :  . 
. of version 3500A may be completed imd  orderlies. or engineers who are in a  whether theo rd evice is available-for.' . .  . 
identically reproduced in place Qf the  position to detect an adverse event  evaluation  is in the manufacturer's 
suspect medical device section (section  involving a medical device.  .  possession. Based on the responSes to  c 
One comment requested that FDA  this section,>ils well as inform)ltion in . 
D) on the front ofthe form. This makes 
provide a way of designating devices  other sections of the form. FDA bflleves  
it posSible for medication manufacturers 
. to subinit all necessary information on. .  thaFtD dAo  rneocto rgenqiuzeirse t ahna_t o tpheerraet oarre   a  bthea at bthlee t aog deentceyr maninde m wahneurfea catsuurseprse c~tl. l . ~ 
one side oftheform.  necessary.. 
significant nlimber of deviceS that do   medical device is located. if
One comment suggested that 
not require operators. In such caSes, the  One comment stated that FD~should 
manufacturers be permitted to submit 
subsection would not apply.     provide "instruction in the proper . 
and refer to the user facility report  . 
Section 0.5 of the proposed form 
 handling of 'explanted' materials; 
rather than repeating the information in  asked for the device's "exp. date." 
 FDA lielieves that such instruction 
sectionD.   
Several comments noted that tlie term 
 could vary, depending on the medical 
FDA agrees with this comment. The  "exp. date could be understood as an 
 device involved, and so it would be   
 manufacturer does not have to recopy  abbreviation of"explant date.~  . 
 impractical, given the limited spaCe on 
the infounation supplied by the user  To avoid any possible confuSion. FDA  the form, to amend the form to provide  
. facility and.may refer to the answer in  .  has replaced "exp. date" with  instructions for every possible type of . 
the user facility/distributor section  "expiration date."    explanted device. FDA acknoWledges. , 
. (section F in version-3500A) ifthe  Section 0.8 ofthe proposed form  however, that the issue raised by the:, 
manufacturer~after conducting an  requested the date on which the suspect  comment is important and intends to 
appropriate investigation, verifies the 
medical device was "removed."' Several  address these issues in the future.  . 
information.  comments stated that the word  Section D.to in the proposed form 
One comment suggested replacing the  "explant" more accurately described the  requested information on "other 
heading, "Suspect Medical Device"  information sought under this  medications/devices used prior to 
with "Subject Medical Device."  subsection than remove.  event" and also requested "therapy 
FDA declines to accept ~s  FDA agrees with these comments and  dates!' Several comments claimed this. 
suggestion. The form is intended to  has changed the form to provide a space  request was too broad or would yield. ~ 
provide mformation on "serious adverse  to indicate the date implanted devices  little value. Other comments stat~ that 
events" and deaths that are suspected of  may have been "explanted.   the requested information might not be 
baing related to 8 device. The term  Section 0.9 of the proposed form  pertinent, and that FDA should limitthe 
"Suspect medical device" quite  asked whether the device was "available  requested information to dtugs or. 
appropriately focuses the reporter's  for evaluation" and whether the device  devices that might have had a hea!fng 
attention to 8 possible association  had been returned to the manufacturer.  on the adverse event baing reported. 
between a serious injury or death and a  Several comments suggested that the  One comment suggested that FDA 
medical device.  agency_should advise user facilities to  amend the form to specify other  , 
FDA. on its own initiative, has  return allegedly faulty devices to  medications or devices that might have 
changed the caption of section D.l from  manufacturers.    had an impact on the event. Another 
"product name" to "brand name."  FDA advises that requiring user  comment suggested the listing ofother 
"Brand name" is more commonly used  facilities to return devices is beyond the  medications and devices in use at the 
in the device industry and _will identify  scope of the user facility reporting   time of the event. 
products with a greater degree of  authority under section 519 of the act  The agency agrees that the proposed 
specificity.  (21 U.S,C. 360i) and accordingly beyond  form's request for "Other medications/ 
Section 0.3 ofthe proposed form  the scope of this report form. User  devices used prior to evant-give 
asked for the manufacturer's name and  facilities should be aware that the  therapy dates," was overly broad-and 
address. Several comments asked  failure to return a device to the  might yield information that is not  31604  Federal RegisteJ; I  Vol. 58, No. 105 l  ThW'Sday, June 3, '1993/.Notices 
pertinent. FDA also agrees with the  FDA declines to amend the:form as.  One comment asked.FDA to.define ,   
comments suggesting listing other  suggested by the comment. There is  "user facility'' ..when.an.adverse,eventis. 
medications and devices in use at the  sufficient space to provide any  being reported by a JDanufacturer. 
time of the event and specifying other  additional identifying information that "  FDA lias deleted this portipn .on , , 
medications or devices that may have  the reporter may believe is useful.    version 3500A. Only the health 
an 
had an impact on  event. Accordingly,  Several comments said section E.2,  professional's form(version 3500) _.,,, 
FDA has deleted the request for "Other  which asked whether the reporter is a   continues to ask whether the. event was 
medications/devices used prior to  health professional, is unnecessary on  also reported to a manufacturer,. u.ser ': . 
event," and replaced it with    version 3500, which is created expressly  facility, or distributor. As for the  <  
"Concomitant medical products and  for health professionals. One comment  definition of "user facility," FDA'has; .  
therapy dates (exclude treatment of  suggested that the form provide space  defined the term in the. next section/<-..  . 
event)." FDA believes that this revision  for a specific health profession.    H. Section F(Version 35DDA dnly}::~6r~   
will provide the key information  Asking whether the reporter is a  Use by UserFacility/Distribrjtor..::'~.;>;;,' 
necessary to determine whether the  health professional is not redundant '  Devices Only.  .  . . ,,.,: :  .  . . 
cause of an.adver8e event is related to '  because version 3500 may be completed          
possible drug or device interactions.  by consumers as well as by health  Section F o~pr~osed;,ersio~3Sb~A~
Other comments suggesJed that the  
 professionals.  ~  :  ..  requested dev1ce . ~ta from user~., ./   
agency amend the form to permit 
 The form includes a space, designated  facilities or distributors. The p~oposed . 
reporters to determine whether 
 section E.3, for the reporter to indicate  secti,on requested 14 .items of  . .. -~ .. '. 
concomitant treatments were.related to 
 .his or her occupation; if the reporter is  information:.(!) Designation.oft!W .~ ..  
the adverse event. 
 a health professional, this is the place to  reporter as either a user facility or:.:. ..
< 
The agency declines to accept this  indicate a specific profession and ,     distribu!~r;J2l a ~po~num'Qe,r,; (~l.~jr;, . 
suggestion. The empJ;laSis on adverse .    specialty.  .  '.  .  .  "  '.  user fS:Clbty sb~ ~.stributor's naw~:~~~;:. 
event reporting is to-identify events and  Section E.~ in the proposed form :for  address; (4) the contact person'~amlr.SF.. , 
possible interactions which are not  health professi9nals pertained to    .(5) the phone immberwl1ere the.:~.\(~' 
already known or, ifknown; occur at 11.  "Occupation." FDA rec:;eived two  .  person can be reached; (6) Ai(l.d~~l'!!~::. 
greater frequency than expected. Thus,  comments seeking clarification as to  ..  e~en~ was reported to the us$rfa~\!fY.'~r 
restricting concomitant products to  whose occupation was being requested.  d1stributor; (?).the; type Qf ~pcm(~1,\i~l 
those which the reporter believes "may  The initial reporter's occupatio1_1  ..  or"followup): (8) the report's dat~;~JP)~:{. 
have had an impact~~may tesult in  should be provided.  the ?evice purc~ase date; (10) e\'E!I}t:~r, 
incomplete information or delay the  G. Section E rVers.io~  0A Oitly.fior  (patumt and dev1ce) problem codell~;(g) 
discovery of previously unknown  .  350 whether a report bas been sent to FD~(
Mandatory Reporting)-Initial Reporter  (12) the location where the event   <'   . 
interactions. 
Section E in the proposed form for  occurred; (13) whether a report was sent 
F. Section E (Version .3500 Only for 
 user facilities, distributors, and  to the manufacturer; and (14) the  ',. 
Voluntary ReportinY-:-Reporter 
 manufacturers also requested  .  manufacturer's.name and address.  
Section E in the proposed version for  information about the reporter{name,  Section F.l in proposed ver8ion  . .  ' 
health professionals requested  '    address, and telephone number),  3500A asked whether the reporter was 
a
information about the reporter (name, .  whether the reporter was a health  user facility or distributor. One ..  .  
address, and telephone number),  professional, the reporter's occupation,  comment asked FDA to define ~mer:..     ' 
 whether the reporter was .a health  and whether the information had been  facility." Section 519,(b)(5)'oftbe act'> 
professional, the reporter's occUpation,  reported to .the manufacturer, user.  defines "Device User Facility" as~ 
whether the information had been  facility, or distributor.  .    "hospital, ambulatory surgical facility, 
reported to the manufacturer, user  Several comments asked FDA to  nursing home; or outpatient treatment 
facility, or distributor, and :w~ether the  clarify who the "rep.orter" is.  .    facility which is not a physician's    
reporter did not want his or her identity  FDA bas modifiea the title of section  office." 
disclosed to the manufacturer.  E of version 3500A to read "Initial  Under section 519(e)(5) of the act, tlie 
Several comments asked FDA to  Reporter." This will allow the 1,1ser  Secretary of HHS may, by regulation;.  
explain who the "reporter" is;  . .  facility, distributor, or manufacturer to  include an outpatient diagnostic facility 
 The "reporter" on version.3500 is the  indicate who reported the adverse event  which is not a physician's office within 
health professional or consumer, who  to it.  the definition "device user facility."  . 
may submit the form to manufacturers,  Section E.4 in the proposed form  FDA, in its tentative final rule published 
user facilities, and distributors, as well  asked whether the information had been  in the Federal Register of November 26, 
as to FDA. Ifone health. professional is  reported to the manufacturer, user.  1991 (56 FR 60024), proposed to include 
completing the form for another, the  facility, or distributor. One comment  such outpatient diagnostic facilities 
reporter on the form should be the .  suggested that FDA add a space to  within 'the definitioq of device user . 
health professional who can be  .  indicate whether the initial reporter also  facilities. Unless and until FDAissues a 
contacted in the event that followup is  sent the report to FDA.  final regulation requiring outpatient 
necessary. FDA recognizes that the  FDA has revised section E.4 to ask  . diagnostic facilities that are not 
hospital pharmacist may serve as the  whether the initial reporter also sent a  physician's offices to submit adverse 
facilitator for reporting by _physicians.  report to FDA. This will allow FDA to  event reports, such entities are not  , . 
Several comments asked for  know whether the initial reporter has  required to report. In the interim, 
clarification of the entry. of the reporter's  also sent the agency a voluntary report  however, FDA encourages the 
name, address, and telephone number.  of the same event .. The agency has  submission of voluntary reports from. 
Two comments asked for specific data  deleted the references to a  such entities. 
entry lines for identification of the  manufacturer, user facility, or  .  Proposed section F.2 requested 
doctor, university, or other relevant  distributor in section E.4 of version  information on the "report number." 
information in addition to name,  3500A because version 3500A is  Seven comments asked FDA to clarify 
address, and telephone number.  submitted by those parties.  the term "report number."  Federal Register I  Vol. 58, No. 105/ Thursday, June 3, 1993 I Notices  .31605 
In response to these requests for  derived directly from the statutory  form it is completing and that agency 
clarification; FDA has revised the   language relating to user facilities in  personnel will be able to determine  . 
wording so that the entry in thq'final  section 519(b)(1) of the act, and from the  quickly whether they are receiving an 
form requests the ..U  F/Dist Repilrt  distributor reporting regulations, part  initial or followup report. 
Number" which is ail abbreviation of  803 (21 CFR part 803), which ~me  Proposed section F.8 ofthe form 
User Facility/Distributor Report  final by operation of law on May 28,  asked for the .. date of this report." 
Number. The number consists of the.  1992. This statutory and regulatory  Three comments asked FDA to 
facility's Health Care Financing  language triggers a reporting  explain how this date differed from the 
Administration (HCFA) number, the  requirement for those entities within 10  entry in proposed 5ection B.4 ofthe   
calendar year, and a consecutive 4digit  days after they are deemed to '"become  form for the "date ofthis report.'' '   
number for each report filed that year by  aware" of the event. FDA. in its  The date ofthe report in section B.4 
the facility, e.g.; xxxxxxx-1991-0001,  November 26, 1991, tentative final rule  ofthe form is the date that the report is 
xxxxxxx-1991-0002. Ifa facility does   requiring user facility reporting, stated  filled out by the reporter, who may or  
not have a HCFA   number, the first.    that the user facilities are deemed to  may not be a user facility or distributfC)r; 
report should be Slibmitted with all  "become aware" ofinformation that  The date of the report in section F.8   
zeros in the HCFA1ipace, and FDA will  triggers the reporting requirements only  refers to the date the user facility or 
assign a number to be used on future  when they have sufficient information  distributor forwards the report tQ FDA 
reports. Ifa facility has more than one  to make a determination that a report is  or the manufacturer. This information is 
HCFA number, the facility may choose  required. Distributors, however, only  relevant because it indicates the date 
any one ofthose numbers, butmust use  serve as a conduit of information  that statutory and regulatory timefr&mes 
the same number fOr subsequent  submitted to them, and are deemed to  for reporting are triggered. (See the  .  
submissions. These numbers; whi!=b   become ''aware" of information that    discussion to comments for section F.6.) 
will be unique to each fonD; will    triggers reporting requirell)ents when 
Propo~section F.9 of the fOrm  .. 
facilitate tracking ~dau,diting by FDA.  they receive a report.,.       asked for the "deviee purchase data."  
Device distributors follow the 8ame  Prop~dsection F.7 requested that   FDA received eight comments on this ~ 
format butuse the~ FDA registration  user facilittesand distributors specify  section. Some comments noted thatthe 
number with the calendar year and  whether the report is an initial or  _ 
device p~asedate was often not. 
sequence nrimber.  '  .   followup report. FDA received four .  >  ; 
acCessible to a distributor: oiber . .  ~/ 
Proposed section F.4 of the form 
 comments on this section. One 
comments sugg~sted.thatit would be ': 
requested that tiser facilities or  , 
 comment suggested mandatory   
more realistic to request the  .  , 
distributors list a contact person..One 
 resubmission of the entire form with 
comment sought clarification as to who  each addendum.  approxi~teage of the device.   . 
The agency agrees that purchase dates 
the contact person should be.  FDA di:;agrees with the comment 
may often not be accessible and that  .. 
User facilitY submissions should be  suggesting mandatory resubmission of 
approximate age of the device is. more 
made by an individual who is   the entire form for each addendum.  
appropriate. Therefore "device_ purchase 
designated by the facility's most  Resubmission of the entire form would 
date" has been revised to read, 
responsible person as the device user  hi~derFDA's ability to determine 
"Approximate age of device." 
facility contact for this requirement.  wliether an initial or followup form was 
Section F.lO in the proposed form 
FDA will conduct its medical device  being submitted _and also inake it   
reporting (MDR) correspondenCe with  difficult to identify new informatiqn.  requests "Event problem codes" and 
this individual. The contact person may  Such resubmissions would also place  refers to a "coding mariual." FDA  .  :' 
received many comments expressing : 
or may not be an employee ofthe  '  additional paperwork burdens on user 
facility. However, the faCility and its  facilities or distril;Jutors without any  confusion over these codes as wellu>.. 
reSponsible officials will remain the  apparent benefit. to the user facility,  the coding manual to be used insection 
parties ultimately responsible for  distrilmtor, or FDA. Consequently, FDA  F.10. 
compliance with the requirements.  declines to require resubmissions ofan  The agency intends to make the 
Proposed section F.6 ofthe form  entire form with each addendum.  Coding Manual available at the time  
. requested the date the adverse event  Another comment suggested that FDA  version 3500A iseffective.... .,
. was reported to Qle user facility or  amend the form so the designation of an  Proposed section F.tt asked whether 
distributor. Four comments said this  initial report or a followup report would  a report had been sent to FDA and. if so. 
date should be the date on which the  appear in a section rpquesting "general  the date the report was sent. 
user facility or distributor determined  information."  One comment said that1he 
that the event was reportable. One     FDA has taken this.comment under  information requested in this entry is 
 comment noted that without requesting  advisement and will consider it after the  redundant to section F.7 ("Type of 
this information, FDA would be unable  agency acquires some experience with  report"). 
to determine ifthe user facility  the final form.  The agency disagrees with the   
complied with the provision in the Safe  One comment asserted that the  comment. Section F.7 asks whether the 
Medical Devices Act of1990 (the  proposed section F.7 did not adequately  information being provided is part ofan 
SMDA) (Pub. L. 101~29), which  d-istinguish between initial and  initial or followup report; it does not ask 
requires user facilities to report an event  followup reports.    whether the report was sent to FDA, nor 
within 10 days after the user facility  The agency disagrees with the  does it ask when the report was sent. In 
becomes "aware" of a reportable event  comment. section F.7 in version 3500A  contrast, section F.11 will inform  . 
u.s.c. 
(21  360i(b)(1)).  permits the user facility or distributor to  manufacturers and others analyzing ~a 
FDA has revised section F.6 to read,  check simply whether the report is an  report whether FDA has also been  
"Date user faCility or distributor became  initial report or a followup report. By  informed of possible problems with the 
aware of event." The agency believes  permitting these parties to check an  device.   
that this language is the most relevant  appropriate box, FDA believes that a  One comment stated that the question 
to the distributor and user facility  user facility or distributor can readily  whether a report had been sent to FDA 
reporting requirements because it is  determine and indicate which type of  could make user facilities and  31606  Federal Register I  Vol.  58, No.  105 I Thursday, Jun,e  3,  1993 I  Notices 
distributors believe that they should   FDA deelines to amend the form as    different from the information-filled out 
send a report to FDA.  requested. The category of "nUf1)ing  in section D.3 orF.14.  .:  ,.  -c:  :_. 
FDA advises that distributors and user  home" is specified in the SMDA, and 
I. Section G(Version 35oOA _bniyf--Ail 
facilities must ,submit reports ofcertain  the "other" option will allow' reporters 
Manufacturers  .    .   
adverse events to FDA. Under section  to indicate different kinds of facilities 
519(b) of the act, a user facility must   that are not specifically indicated on the  Section G in the proposed, fonit for 
submit reports of deaths that are  form.  user facilities, distributorS, and  ,   
suspected of being device related to  One comment suggested changing 
 manufacturers requested inJormation 
FDA and to the manufacturer, if known.  "ambulatory/surgical facility" to   
 from all manufacturers, inCluding tbe 
User facilities must also submit reports  "ambulatory surgical facility." 
 manufacturer's name, addre~. and -: 
nf serious injuries that are,suspected of  FDA agrees with comment and has 
 telephone number, the report sourt:e  . 
being device related to the manufacturer  changed the form accordingly. 
 (such as literature, health professional, 
or, if the manufacturer of the device is  Proposed section F.13 ofllie form  user facility, etc.), the date th~    
unknown, to FDA. Similarly,  asked whether the user facility or  manufacturer received the report, th5J. 
distributors are required by regulation to  distributor had sent a report to the  application number if the report. 
submit all reportable adverse events to  manufacturer, and the date of such a  involved a human drug product, the. . . . 
FDA and to the manufacturer. Thus, the  report. One comment expressed concern  type of report, the adverse event term(s) 
statute and regulations do require user  over the accuracy of the _information  (for a biological product), and the  . 
facilities and distributors to report to  provided to the manufacturer.  report/control number.  . 
FDA.  The agency is aware that information  . Section G.1 in the proposedform  . 
Proposed section F.12 listed seven .  provided to manufacturers may be  requested the manufacturer~s nam~,,..   
possible choices-"hospital," "J;10me,''  anecdotal or incomplete, but notes that  address, and telephone number:  -: 
"nursing home," "outpatient treatment  it is the manufacturer's obligation to  FDA has, on its own initiative .. 
facility," "outpatient diagnostic  .-   investigate reports of adver8e events  '  chariged the desCription of the' <  .. 
facility," "ambulatory/surgicat facility,''  related to their devices.  .  information &Qught in section G.11.d.: 
and "other"-for the location at which  Proposed section F.14 of the form  identify a "ContaCt offi~name(: ' .. 
the adverse event occurred.  asked user facilities or distributors to  address (&:miring. site for devices)/':In  _ 
bne comment questioned whether the  provide the manufacturer's name and  addition, FDA has created a new:S8Ction 
< 
request for"location" referred to the  address. Three comments claimed that  G.2 for the. contact office'stelephoD:~-
location ofthe adverse event or the user  this provision duplicated information  number. 	 - .  'I..:-~.,>, 
facility.  .  requested in section 0.3 t'Manufacturer  Section G.2 in the proposed fo~,:1if\
The "location" request in the form .  name &: address")-and section G.l    (now renumbered as G.3) requested,"~'.;; 
means the location where the adverse  ("Manufacturer name/address&: phone  information on the report source. the:~
event occurred.  # (site of mfr for dJ.vice)") (now  section lists several possible sourc~. {; 
Thirteen comments asked FDA to  "Contact Office name/address (&: miring.  such as "foreign," "study," "literature,'' 
delete "home" from the form. Several  site for devices")}.  . .  "consumer," "health professional,'~ user 
comments stated that reporting home  The agency disagrees with the  facility," ''company representative.~ 
events is not required under the SMDA.  comments. The three sections cited by  "distributor," and "other." Several 
One comment suggested putting  the comment can result in different  comments said that "company . 
"(voluntary)" after the entry for  manufacturing names and addresses  representative" Should be deleted  . 
"home."   from different parties. Section D._;J, for  becaul!O the report source_should be the 
FDA does not-agree that the reporting  example, which requests the    original reporter;    - . '  , 
of certain events that occur in the homlt  manufacturer's name and address for  FDA disagrees With the comment.- . 
is~ot required under the SMDA. For  the suspect medical device, may be  FDA recognizes that certain-segmentSof 
example, a distributor thatbecomes  completed by a voluntary reporter. This  the industry frequently receive reports 
aware that one of the-devices-it  individual will probably only haw  from company representatives. :rhe   -; 
distributed is suspected of causing a  access to the device itself and will  .agency wants to track reportsrect~ived 
death or serious injury while being used  therefore supply the name oraddress of  in this manner.      .   
in someone's home must report this  the manufacturer that is imprinted or  One comment suggested designating 
event to FDA. Accordingly, inclusion of  attached to the device. In contrast,  the last four items in..the_list of report  
the choice "home" hi F.12 is    section F.14, which fs completed by the  sources (user facility, company_ 
appropriate and should not be followed  user facilities or diStributors, will  representative, distributor, and other) as 
by the word "voluntary:"  .  provide the manufacturer's name and  being relevant to dev~ces only, and 
Another comment suggested adding  the address these reporting entities U:se  another suggested adding "foreign 
"home" as a possible location of the  for the purpose of communicating  health authorities." One comment 
adverse event to version 3500, the  adverse event information to the  objected to the use of the term 
voluntary form used by health  manufacturer. The-name and address  "literature." 
professionals.  may be different from the manufacturer  The proposed form did include~ and 
FDA does not believe it is necessary  name and address present on the device  the final version retains, the choice of a 
 to include this information on the  itself. FDA has revised the request for  "foreign" source. However, FDA has not 
voluntary form. The agency will have  information in section G.l of the final  revised the form to make the other 
this information for all deaths and other  form, which is completed by  suggested changes. FDA realizes that 
serious adverse events on the report  manufacturers, to clarify that the  "user facility," for example, may only 
form submitted by the distributor andt  manufacturer must identify both a  be relevant to device-related adverse 
or user facility.  .  contact office and include the name and  events. The purpose of this form, 
One comment suggested changing  address of the manufacturing site for the  however, is to provide one form that can 
"nursing home" to "residential care.  device. The contact office and  be used to report adverse events that are 
facility" in order to encompass a  manufacturing site information  related to several FDA-regulated 
broader range of institutions.  provided by the manufacturer may be  products. It is therefore necessary to  Federal Register I  Vol.  58, No.  105 I Thursday; June 3.   1993 I  Notices  3,1607 
include some choices in this section  under section .StO(k) of the act (21  ,  comments asked whether this 

that may not b&.relevant to a specific  , U.S.C. 360(k)) or the premarket approval  information could be moved to section  

FDA-regulated product. FDA also does  application (PMA) number for medieal  B ("Adverse eventorproduct  _ 

not agree with the comment which  devices. One comment suggested they.  problem"), Some comments Said that 

objects to the request for "literature" as  be included.  the preprinted Jines l~mited.the number 

a report source. FDA regulations at  .  FDA has not required the 510(k)  .  of terms that coul!f be provided.  . .. 

 314.80(b) provide that each applicant  num~ror the PMA number on version  FDA has revised the form to delete the 
having an approved application under  3500A because this information would  term "Biologics" because the agency did 
21 CFR 314.50 or 314.94 shall promptly  duplicate other information FDA may  not intend to. limit the applicability of 
review all adverse drug experience  receive in periodic reports from device  this section to biologics. FDA has;also 
information obtained or otherwise   manufacturers.  deleted the preprinted lines.FDA. 
received by the applicant from any  Two comments asked whether reports  declines, however, to move this   .  ...; 
source, foreign or domQstic, including  for investigational deviceBXemptions  information to section B because the  
information derived from commerCial.  (IDE's) are to be included in this form.  a_gency believes this informationis:best  ,  
I  marketing experience, postmarketing.  Devices that are subject to IDE's~.  hnked to other information prov.ided by 
clinical investigations, postmarketing  pursuantto 21 CFR parts 812 and 813  the manufacturer in section G.  ..:  .  
epidemiological/surveillance studies,  are exempt under 803.36(b) from the 
Section G.8 in the proposed form 
scientific literature, and uripublished  adverse event reporting requirements. 
 (now repumbered as G.9) requested:the 
scientific papers. Current regulations for  These devices are instead subject to IDE 
"Repprl/control #1. '' Severalcomroents 
device manufacturers and distributors  I:eporting requirements.    . .  . 
also require submiSsion of reports_ from   One comment asked whether the form  sought clarification. of this sectio~. One 
any source, including literature (see-part  should be usedJo .report adverse events  comment-asked how th" reporl/ccm~l . 
number differed from the manufacturer :   
803). Thus, the form appropria~ely lists  for IND products in development. .,.  . report n\upber. Another eomroeilinoted ; 
possible sources of reports~  .  .    Adverse events associated wi~these 
Section G.3 in the proposed form 
 . products should be reported. FDA Fo~  ~at the manufacturer report.num~~is . 
already required at the top oftheJorm' . 
(now renumbered as G.4) requested 
 3500A is not required but may be.used . 
and questioned wby manufacturers: 
information on the "date received by 
 to report tQ-dayiND safety alerts. One. 
. manufacturer." FDA received several  comment asked whether, for marketed  should provide the number ln.s~Qn 
G.8 (now renumbered as G.9).   
commQnts requesting clarification of  biologic products, both the IND and the 
FDA.has revised both entries to read 

this date. Two comments wanted to.  PLA numbers_should be provided 'for 
"Mfr. report number." The  :.  . 

ensure that the date meant the dattrthe  spontaneous postmarketing reports and 
manufacturer report number is required 

manufacturer received enough  asked about products with multiple ..  
in both places to allow the front .and ..   

information tb make a report, and one  IND's butonly one PLA.  .   
asked whether the date meant receipt of  For a markete4 Dialogic product, the  back pages of a particular report.to be 

.. information by the corporation .  .  .  PLA number should be provided for  matched in the event they are submitted 

anywhere in the world or in the United  spontaneous postmarketing reports. The  as. separate pages or if they are copied 

as separate pages.  

States.  '  .  IND n\lmber should only be referenctKi 
The date received by manufacturer  ifthe'suspect product associated with  f. SectionH(Version 3500A Only~ 

means the date the manufacturer  . the adverse event was administered.  Device Manufactilrerspnly     . 

initially received information to  under a specific IND protocol, and the 
determine that-an adverse event  report is being submitted as a tO-day  Section H in the proposed form for 

occurred. This would apply to a report  IND Safety Report. .  .    user facilities, distributors, and . 

received anywhere in the world.  .  One comment said the .form should  manpfacturers requested device     

Section G.4 in the proposed form  ask whether the product is an over-the,. manufacturers to provide 13 items of 

(now renumbered as G.S) pertained to  coup.ter (OTC) product~ .  . information: (t)A~ontact office,  .1-. .... 
an NDA number, IND number, PLA  FDA agrees and has revised the. form  including an address and phone  .  
number, and asked whether the drug  to include a box to indicate whether the  number; (2) the device manufacture 

product was a "pre-1938'' product. One  reportconcerns an OTCproduct.    date: (3) the product code; (4)wbether  

use: 
comment suggested that the form either  Section G.6 in the proposed form  the device is labeled f~r single  (5) 

specify that the acronyms (NDA, ANDA;  (now renumbered as G.7} concerned the  the report type; whether it con~rnsa 

etc.) pertain only to pharmaceutical   "type of report" and included six  death, serious injury, a malfunction, or  ~ 

manufacturers or spell out the terms.  possible choices: 5-day, 10-day, 15-day,  some other problem; (6) whether the  . 

The acronyms pertain to human drug  initial, periodic, or followup. One  event being reported hivolved the initial 

products. "ANDA" stands for  comment 'said that the form repeatedly  use or reuse of the device; (7) whether 

"abbreviated new drug application;"  asks whether a report was an initial .  the manufacturer has evaluated the 

"NDA" stands for "new drug  report or a followu{>.  .  device, and, if so, whether it has 

application;" "IND" refers to an  FDA disagrees w1th the comment. The  conducted a failure analysis; (8) .jf the 

investigational new drug application,  designation of an initial or follo\vup  report is a followup report, whether it 

and "PLA" refers ~o a "product license  report by manufacturers only appears  reports a correction, provides additional 

application." The agenJ;y has not,  once onthe form.  information, responds to an FDA 

however, revised the form as the  Section G.7 in the proposed form  request, or involves .a device evaluation; 

comment suggests because it believes  (now renumbered as G.8) concerned -.  (9) evaluation codes, including entries 

medical device arid drug and biological  "adverse event term(s)" for biologics  for method, results, and conclusions; 

product manufacturers know what  and provided three lines for entering  (10) the type ofremedialaction 

abbreviations are applicable to their  .information. FDA received many  initiated, such as recall, repair, or 

products.  .  comments noting that the information  replacement; (11) whether the action 

Several comments asked why the 
 was requested only for biologics and  was being reported to FDA under FDA 

form did not request the application 
 asked whether FDA intended to limit  regulations; (f2) a manufacturer 

numbers for applications submitted 
 this section to biologics. Several  narrative, and (13) corrected data. 
 31608  Federal Register I  Vol. 58, No.  105 I  Thursday. June 3, 1l93 I Notices 
FDA, in response to comments and on  guidance will be issued by FDA by the  be "helpful in clarifying the nature of 
its. own initiative. has significantly  effective date of this form.  tile particular problem!'      -, 
reorganized and reVised this section.    One comment objected to including  FDA does not agree tllat adding tllese 
Section H, as revised. assigns greater  _  "other" as a type ofreport, stating that  entries under the user facility/ 
prominence to certain entries, such as  the SMDA only requires reports of  distributor rep?rting section will 
the type of reportable event and whether  death, serious illness, or serious injury.  provide clarifying information. The user 
the manufacturer has evaluated the  Another comment asked whattype of  facility and distributor reports are  
device. and deleted the entry  event would fall under this category.  forwarded to tile manufacturer. The    . 
concerning "product code." The agency  The form's reference to "other" is  manufacturer must then submit a report 
will discuss these comments in the  intemted to capture any reports that a  based on tile distributor or user facility 
order in which they relate to the  manufacturer believes the agency  report indicating tile kind of followup  
sections in the final form.  should be aware of that ar&1lot covered  report. Accordingly, requiring this 
Section H.I in the final form requests  by "death," "serious injury, and  information from user facilities or  
information on the "Typf:r ofReportable "malfunction," as these terms are  distributors would provide duplicatiVe 
Event." This section was at H.s in the 
 defined by statute or regulations. This  information to FDA. 
proposed form, and was originally 
 category can be used to notify FDA of  Section H.7 of tile propoSed form, 
captioned .. Type of Report.'' Several 
 ~ correction action or removal. Section  "Device evaluated by mfr7" (now    
comments stated that the information 
 519(f}(1) of the act states that no report  renumbered as H.3 in the final foriJI), 
 requested in this section duplicated that  Ofcoi'J'8Ct_iv~ action or removal is  contained tllree boxes tllat device   
requested in section 8.2, "Reasons for  . required 1f 1t has been reported per  manufacturers could mark: "yes,'' .: . 
reporting adverse event.''  section 519(a} ~fthe aC!-. Moreover,  "failure analysis attached;" and "no (if 

FDA disagrees with the c:Omme~ts.  under the Med1cal DeVIce Amendments  no, attach page to explain why not) or . 

Section 8.2. which is now titled,  ,  .  of 199~: the category can be used to  . providecoC:le.',' Two1:omments said   

"Outcomes attributed to adverse event,''  repo~ other signifi~t adverse device  FDA should delete this section or; if 
applies to medications, medical devices,  expenence as determmed by the  retained, change "failure analysis 
and otber-FDA-iegula:ted products.    Secretary,!o be necessary to be  attached" to "evaluation ~mmary 
Consequently, it identifies possible 
 ~~~H.a ofthe proposed form  attached.''  . 
FDA disagrees tllat tllis section;gl1_ould 
adverse events or problems, such as 
 (now renumbered as H.-2 in the final  be eliminated. It is tile nianufa~r's- 
congenital anoma~y, that ~aynot be 
 form)"was captioned, "If follow-up,  primary responsibility to determiJ!e . -. 
.appll~ble to medica.} deVIces. In  what type?" The form provided four  whetller its devices have caused an"" . :_ 
contrast, section H..t is-devoted  boxes to indicate whether the followup  adverse event and, in turn, to provide''' 
exclusively to medical device  was a correction, additional 
such information to FDA so tile agency 
manufacturers and is specific to the  information, response to FDA request,  are, 
can determine whether further steps 
categories of adverse ev;ents ..that device  or device evaluation. Several comments 
needed _to protect tile public health. The 
manufacturers are tequlr8d to report.  requested clarification. One comment 
agency agrees, however, tllat tile term 
Further, the agency anticipates tllat    asked whether a manufacturer had to 
"failure analysis attached" might be 
secti?n 8.2 will ~~alninformation  complete a new form whenever new  interpreted to preclude any other  
proVIded by tile m1tial.reporter, such as  information became available. Anotller 
evaluation outcomes an~ has replaced it 
a user facility, and forw.ar.ded.to the  comment requested clarification of tile 
witll "evaluation summary attached.'.' 
manufacturer. After an mvestigation, tile  term "correction." A tllird comment 
Another coinJ!lent suggested -tllat a 
manufactun:r's interpretation of tile  .  asked whether the agency was trying to  manufacturer may be unable to conduct 
event ~aydi.ffer hom that provided by  determine whether a report was an  an evaluation -for alltypes of devices, 
the tmtial reporter.  original or followup report;  . 
notably devices that are dis,P-osable. 
S6Veral comments requested tllat FDA  Section H.2 is intended to assist  The agency advises manufacturers 
chan'ge tile phrase "malfunction tllat  agt!ncy personnel swiftly determine tile  who believe that tlley cannot conduct an 
might cause deatll or. serious injury if it  purpose behind a followup report. For  evaluation for a medical device to usa  . 
were to recur" to "malfunction tllat is  . example, a "correction" would indicate  tile "no" option and attach an 
likely to cause <).eatll" in order to  tllat the manufacturer has alfeady  explanation or provide tile appropriate 
conform to section 519(b)(1)(8) of tile  submitted a report and is correcting  code. Ifthe manufacturer believes tllat 
. act and 21 CFR 803.24.  information provided in tile previous  direct evaluation is not applicable, tile 
FDA has amended tile language to  report. Iftile manufacturer indicated  manufacturer, in some circumstances,  
refer only to a "malfunction,'' Th'8  that it was responding to an FDA  cou!d perform a surrogate method of 
agency notes tllat, under tile 1992  request, tllis would alert FDA personnel  evaluation. 
amendments enacted on June -16, 1992,  to tile possible existence of documents  One comment suggested tllat FDA 
Congress has changed tile standard for  or discussions on the adverse event or  create an additional box to indicate ~not 
determining when adverse events must  product problem. FDA does not expect  returned." 
be reported. This law will be effective  device manufacturers to submit reports  FDA agrees and has added a modified 
1 year from tile date of enactment of  that contain information tile agency has  version of this suggestion, "not returned 
these amendments. Moreover, FDA has  received in a previous report. The  to mfr.'' to the final form.   
not yet published a final MDR reporting  manufacturer should simply provide the  Several comments said FDA should 
regulation, based on comments  new information to FDA and mark the  delete section H.2 in the proposed form, 
submitted in response to the November  box indicating what kind of followup  "Device manufacture date,''. (now  . 
26, 1991, tentative final rule.  report is being submitted.  renumbered as section H:4 in tile final 
Accordingly, at the time of publication  One comment suggested that FDA  form) because it duplicated information 
of this notice, it is impossible to provide  place a similar entry regarding the type  requested in section D.6, which askS for 
tile exact standard that will be required  of followup report in section F for use  the suspect medical device's model 
for reporting under the new law and  by user facilities and distributors, The  number, catalog number, serial number, 
future regulations. Regulations or other  comment said such information could  lot number, and other numbers.  FDA disagrees with the comment. .  concerns labeling information;  Section H.~ "Usage of Device," in the 
These two sections provide different  Information from this section is not  proposed form, isnow renumbered-as. 
information to FDA. Section 0.6 does  intended to be used to interfere with the  section H.81n the final fomi. The   . 
not request the manufacturing.date; it  practice of medicine; it is intended to  proposed form offered three options: "  
merely provides inf~ation th!lt will  provide FDA with information to carry  "initial use of device,"."retise,". or:.. . ;;, 
help identify a speCific medical device.  out its statutory obligation to protect the  "Unknown." One coinment claimed this 
This information may help FDA  public health. Information from this  section was not relevant to medical : -. 
determine whether a specific device  category may, in tum, be provided to  devices.    .  >-. 
design is a problem. Section H.4 asks  health care professionals to make them  For the reasons stated :in FDA's ... '  : . 
when the device was manufactured; this  aware of unsafe devices for the  response to comments to sectionIi.cS, 
(
information may be important shoul~  protection of their patients.  FDA disagrees wciatnh  this commteon V  ."  ;'., 
the manufacturer or FDA determine that  FDA has enlarged and reforoiatted  Adverse events  be related reti8e ~ ~-.: - , 
a
the adverse event may be caused by  section H.9, "Evaluation codes; of the   of devices orily intended for  single , ..  ;: 
manufacturing problems during a  proposed form" (now renumbered as  use. Moreover, this information-may~  . 
certain time period.  section H.6 in the final form). Several  help FDA to determine:whether fhe ..  
Another comment noted that the  comments said FDA should eliplinate  adverse event -is attributable to the  '' 
manufacturing date ''may not be readily  this section because -it was too narrow  device or to its operation and , 
available for large equipment" and  and called for subjective judgments  maintenanGt;J.   ., _ .  .  ~~ 
asked FDA to delete this item.  rather than objective facts.  In sectioJ! H.12 in the proposed fo:nn; - 
FDA does not agree with this  FDA does no_t agree with these  "Manufacturer narrative," (now 
comment's suggestion. As discussed  assertions. Although all codes require a  renumbered and renamed as section 
above, determining the manufacturing  measure of subjective evaluation, they  H.lO, "Additional manufacturer 
date of a product is extremely important  also enable reviewers to ascertain very  narrative,': in the final form) two  ._-, 
in enabling FDA to trace device defects  quickly certain key facts. Manufacturers  comments questioned how this  ~"' . ~:
to flaws in the manufacturing process.  have, or can obtain, the best initial  manufact\lrer narrative differed from the. , . 
Consumers, health professionals,  assessment of the product problem, and  narrative requested in section B.5, .  .  . ,. /- 
distributors, and others affected may  this will help FDA and the  .. Describe event or problem ....:       :
then be informed with some precision of  manufacturer determine the caus~ of the  FDA notes that Section H is to be  ~ 
the products posing a, risk, and any  problem and take any steps necessary to  completed solely by device  n-,.  
possible recall can be limited to the  protect the public health.  --    manufacturers. In contrast, section 
period in which the manufacturing flaw  Section H.10 in the proposed forDJ.. "If  "Adverse eventor product problem.!~ 
appeared.  remedial action initiated, check type,"  may be completed by individuals or  
One comment asked that, in order to  (now renumbered as section H.7 of the  entities other than device 
reduce the burden on manufacturers,  final form) provided nine boxes:  manufacturers. The accounts of the 
the manufacturing date should be  "recall," "repair," "replace,"  event by the' manufacturer in section H 
changed from month, day, and year to  "relabeling," "notification,"  may differ from the accounts presented 
month and year only.  .  .  "inspection," "patient monitoring,"  by others in section B. This is   
FDA agrees and has revised the final  "modifications, adj.," and "other" that 
 particularly true because a manufacturer 
 form to request only the month and  . device manufacturers could select. FDA 
 is obligated to investigate the causes of 
year.  .  .  received two comments on this secti-on. 
 the adverse event, and is therefore likely 
Section H.4 in the proposed form  One comment noted that some terms  to have additional information. FDA, 
(now renumbered as section H.5 in the 
 had not been defined, could "overlap,"  however, does not wish the  _ 
.f inal form) asks whether a device is. 
 and requested clarification.   manufacturer to duplicate information  
. "Labeled fot: single use." FDA received 
 Most of these terms are defined or  that h'ls already been provided in 
!wo comments suggesting that the 
 further explained in the act or in  section B. In order to clarify that the .. 
S9ction was not relevant to devices. 
 existing FDA regulations concerning  manufacturer should. only include in 
Another comment requested 
 recalls and remedial action (see 21  section H.lO information that is 
clarification of this provision. 
 tJ.S.C. 360h and 21 CFR parts 7 and  additional to that in section B.s. FDA 
FDA does not agree with the assertion  803). FDA believes that the remaining  has renamed section H.10 to request  
that the section is not relevant to  terms are self-explanatory.lfa  "Additional" manufacturer narrative. 
devices. FDA is aware that adverse  manufacturer believes there is some  In the proposed form, the  .  .  
events can arise from the reuse of  overlap or that more than one_ type of  manufacturer could indicate in section 
devices that are intended to be used  remedial action applies, more than one  H.13, "Corrected data," (now 
only once.  box may be checked.  'renumbered as H.ll in the final foim) as 
Another comment stated that this  Another comment suggested that the  an alternative response to the proposed 
 sectiog. was not relevant to capital  "recall" .option be placed.in section  section H.12 request for "Manufacturer 
equipment.  H.ll (now renumbered as section H.9 in  narrative." One comment suggested that 
Ifthe section is not relevant to the 
 the finartorm) which requests that, if  FDA replace "12. manufacturer 
device being reported, such as capital 
 action is required under 21 U.S.C.  narrative or 13.corrected data" witha 
equipment, the "No" box is the 
 360i(f), the corraction or removal  reference to the manufacturer narrative 
appropriate selection.  . 
 reporting number be listed.  _  "and/or" corrected data, to clarify that 
One comment asserted that this  FDA believes the current format more  both sections could be-checked or only 
section constituted FDA interference in  clearly presents the requested  one section. 
the practice of medicine.  information and allows FDA to  FDA agrees that both sections or one  
FDA does not agree with this  determine quickly what remedial action  section could be checked and that "and/ 
comment because the requested  has been taken by the manufacturer.  or" language is more appropriate. 
information is part of section H of the  FDA also advises that the proposed  Device manufacturers could provide 
form which only requests information  form stated an incorrect citation, which  "corrected data" in addition to a 
from device manufacturers and  has been corracted.  "manufacturer narrative" or, under  31610  Federal R~ster~,(...yol. Ji8, No; 105/.Thursday, CJune  3, 1993, /:Notices 
certain clrcumst~ces, could provide  not to ~ycOrrections the manufacturer  FDA received many.comments on 
only corrected data; or. only '.'aqditional  may have made to the ri:u!<ij.cal device or  section H.3. "Product COde/' hi 'the  -< 
manufacturer 118rrative." Aceor~gly,.   .to data supporting the safety or  . '  proposed form. The crimments ' 
FDA has revised this section to read   effectiveness ofthe device.  expressed confusion over:what 
"10. Additional manufacturer narrative  -Consequeiitly; this option hidicates only  infoimation W&s being requested. . 
and/or 11. Corrected data."  .  .  .theJonni!tbeing corrected, an,d a 510(Ji) ' 
One commentrequested clari.ficatlon.  or PMA S\lpplemerit will not be  . .  .  FDA has deleted this ~on. 
ol"corrected data." Another comment.   necessary unless otherwise required  .  The following versions ~:th~ fo~ 
-asked whether checking the ~correct~  under FDA regulations.  that appear on the next page are a 
data'~ box would require the    ..  In addition, the agency, on its own  . represe11tation and are not tlie actual 
manufacturer t.o submit a 510(k) or PMA  initiative, has deleted draft section H.l,  si~..    ..   
supplement.   ..    captioned, "Contact office-:4nclude .;__  -:::::nated: May 2~,1wa.  
.  The "correction.. option is only to be  address and phone ifdifferent from G.1" 
David A.~~.' .. 
used to indicate changeS to infOrmation   from-section H, and merged the   
Commissioner ofFood and Dross. 
previously submitted. Itrefers to ,  information request with section G;l  .I  .  ' 
corrected information in the form and   ("COntact offictJ.;-name/address"}.  IIIUJtl c:ooe: 4ttO-Ot-l' 
.  ....,: .. 
. ...  Federar llegister l  Vol~.58, No.  105 I Thursday, June 3, 1993 I !'~latices  31611 
MED~icH  Fur VOLUNTARY rcportin~:  Fonn Approved: OM8 NSo.. .O OltMG-B0 2se9.1& Eempetnrle os:n ' 2ff1t3W11:9M4 
by health professionals uf adverse 
-events and product problems 
IUJ: H>,, "HIJIC'AI. titOUU<"I"' Kfi"UKliNt:~ PKtHOit.\M  Page  of 
A.  Patient information  .      C.  Suspect medication(s)   
1. Patient identifier 2. Age at time  3. Sex  4. Weight  1- Name (give labeled strength & mfr~abeler,_if known) 
oofr e-v-e-nt-: -------------- -0 female  ---- lbs  #1 
or
Date 
In confidence  ofblrth:  Ornate - kgs 
B.  Adverse event or product problem  2. Dose, frequency & route used  3. Therapy dates (if unknown. give duration). 
lrom lo tor best esltn'l8tit! 
1.. 0  Advetee event  and/or  0 Product problem (e.g.. defectsimaHunctions)  11  #1 
2. Outcomes attributed to adverse event  0 
(check all that apply)  disability 
0  0 congenital anomaly 4. Oiagnosi_s lor use (ondocation)  5: Event abeted alter use 
death  0  stopped or dose reduced 
0  required intervention to prevent  #1 
q lifelhreatening,..,.,oay "'  permanent impairmenlldamllge  1 Qyes Ono O~t't 
hOspitalization -Initial or prolongoo  Oo~r;  '  1::6#~.27L o":"t:-:l::-(:::if-;-k-no-wn"-:".)-------r7:-.~E=-x-p-.-:da~t-e-:-(,-:-:fk~n-o-w~n)--1 ,2 Qyes 0 no  Omfy"' 
3. eDvaeten to f  r4.. tDhaist ereopl ort  # 1  '1  8. Event reappeareod a=lter  
lrfiO.dayYrl  tfllOday)'fl  reintroduction 
5. Describe event or problem   #2  #2 
-:-:NDC=~,-:-(f:-_or-p-r0d-:-u-cl_p_ro7blems:--_"-onl-:y-:-)----.,.--f  1  D
..  \ 1::9-. 11'  Oves  no 
.2 
Qyes Oi.o p=n, 
tO. Concomitant medical products and therapy dates (exclude trea~of event) 
D.  Suspect medical device  ,. 
1 Brandname 
2. Type of devi_ce 
3. Manufacturer name & addraaa  4. Operator of devica 
0 
\  health professional 
0 
.lay user/patient 
0 
other: 
- ----' 
5. Expiration data 
6.  ~moc&a;yrl
model I 
6. Relevant tesfsllaboratory data, Including dates  7. H implanted, give date 
catalog I 
1modayyr1 
serial I 
8.  H explanted, give data 
loll  lmodayyrl 
other II 
9. Device available lor evaluation?   (Do not send to FDA) 
0  yes  0  0 
no  returned to manufacturer on 
10. Concomitant medical products and therapy dates (exclude treatment of event) 
1.  Othenelevant history, including preexisting medical conditions (e.g.. allergies. 
race. pregnancy. smoking and alcohol use. hepatic/renal dysfunction. etc.) 
E.  Reporter (see conftdentiality section on back) 
1.  Name, addraaa & phone I 
13. 
2. Health-professional?  Occupation  4. Also reported to 
0  0  I  0  manufacturer 
Mall to: 	 MEDWATOi  or FAX to:  yes  no  0 
R56o0c0k vFiilsleh,e MrsD L a2n0e8 52-9787  HIOO-FOA-G178  5.  1H1 Myo mu alinDu NleOctTu wraar,n pt lyaocuer a ind en Xti t"y  Idni sthcilos sbeod .t o O  0  duissetrri bfauctoilirt y 
FDA Form 3500 (6193)  Submission of a report does not constitute an admission that medical personnel or the product caused or contributed to the event.  31612- Federal Register./ Vol. 58, Nq. 105 I Thursday, June 3, 1993 I Notices 
ADVICE ABOUT VOLUNTARY REPORT~_N9 
.. 
,~  '.
Report experiences with:  How to report: 	 . _  _  . 
 medications.(drugs or biologics)  _   just fill in the sections that applyto yo~r:;!9pbrt, . /!J:'
 medical devices (including in-vitro diagnostics)    use section c toran productsexceJ)t' .;.x;~-.::.:-:':'!::);:_  
 special nutritional prc;>ducts (dietary  medical devices  
supplements, medical foods, infant formulas)   attach additional blank pages if needed . 
 other products reguf~ted by FDA   use a separate form for each patient .  . 
~~~~~~ther  ~oA ?~ t~e ma~;<3~P:~~~Jt~~f~-E:_ 

Report SERIOUS adverse events. An event 
 . to_ 
is serious when the patient outcome is: 
 ,, 
~"  '  ~-~:""'. ~-
 death  Important numbers:  __ 
 fife-threatening (real risk of dying)   1-800-FOA-0178  to FAX report . 
 hospitalization (initial or prolonged)   1-800-FOA-7737: to report py modem  ., . 
 disability (significant, persistent or permanent)   1-800-FDA-1 088 16r more information or to 

.  congenital anomaly  report. quality-prOblems . 

 required intervention to prevent permanent 
  1-800-822-7967 	 for~ VAERS fOrm 

impairment or damage 
 . for VClcc,ines 

'  ~ ' ~  -- .  ... 
Report even if:  If your report involves a serious adverse   / 
event with a device and it occurred in a facility ouF_ 
 you're not certain the product eaused the 
side a doctor'soffice. that facility may be legally required  8 
event 
 to report to FDA and/or the manufacturer.  Please notify  ~' \  ;:.-;  ._ ....
~- _you don't have all the details 
 the person ln that facility,who would handle such-reportjn.g...,. .-..:,.:-:_.- . A1  

Report product problems - quality, performance  
Confidentiality; The patient's identity is held in strict ,. 
or safety concerns such as: 
confidence by FDA and protected to the-fullest extent of 
'' >.suspededcontar{iination  the law.  The reporter's identity may be shared with the 
 questionable stability  manufacturer unless requested otherwise. However,  _ 
FDA will not disclose the reporter's identity in response to 
 defective components 
a request from the public. pursuant to the Freedom of   
 poor packaging-orlabefing 
Information Act. 
:.' 
_   The public reporting burden lor this collection ot inlormatton  -Reports Clearance Officer. PHS  and to:  Please do NOT 

has been estimated to average 30 miriutes per response.  Hubert H. Humphrey Building.  Off1ce of Management and  return this form 

including the~time. for reviewing instructions. searching exist~  Room721-B  Budget   to either of these 

lng data sources. gathering and maintaining ltw! data needed. '  .200 1ndependence Avenue. S.W.  Paperwork Reduction Project 
and completing and reviewing the CoUection of information.  Washingtpn. DC 20201  (0911).()291)  .  addreSseS~ 
Send your comments regarding this burden estimate or any  ATTN:PRA  Washington. DC 20503 
other aspect of this coUection of information. Including sug
.gestions lor reducing this burden to: 
FoAForm3sQO-back  Ple~se Use Address Provided Below-Just Fold In Thirds-, Tape and Mail 
------------------------------------------------------------~-------------~------~--------------~~-----------~ 
Department of 
Health and Human Services 
Public Health Service 
Food and Drug Administration  
Rockville. MD 20857 
Official Business 
Penalty for Priv;Jte Use $300 
MED~TCH 
The FDA Medical Products Reporting Program 
Food and Drug Administration 
5600 Fishers lane 
Rockville, MD 20852-9787  _F8deralltegister I  Vo~ -58, No. 105/ Thilrsd&y, June 3, 1993 1 Notices  . 31613 
,OMIINo.OOI~IE
...  r.........'. ... S..OUBIItMMM.n.t...o\.n:
,:..1.../.N.M  

Flll' usc h~; user~facilities, 
MED~TCH 	 distributorS and manufacturers for  ,=-~. 
- MANDATORY reporting
A.  Patient information  .  .   C.  Suspect medication(s)  -.   
known) 
1. Patient Identifier 2. Age at time  3. Sex  4. Welght I. Name (gille labeled strength & mfi-flabeler. d 
oof erve-nt-; -----'-- 0 female  ---1bs II 
or
Oate ___ 
Bt.n  cAondfidveencres e evoef bnirtt ho: r product problemD ma~e  ---kgs 2. Dose frequency & route used  3. Tkhoemr-ap1y0 \da0tfe~sl (r~t_ unknown..  give duration) 
1. 0 Adverse event  and/or  '0 Procluc:t j)rObfem (e.g.: c:tefectslmatiunctionsl  t. 
2. 	(Ochuetcclo<m al1e sth aattt raipbpultye) d to adverse even,. t  o0  cdoisnagbeitni'tXta l anom aly 1  .#42,. _  Diagnosis lor use (tnd<calton)  5. 	Event abated after uae 
00O  dehlnoaes t-pthhit raelaiztaetnioinngt  m~:oind iatyia'y ln  or prolonged  0O  ropeetqhnuenirrae:n.de  nintt eimrvpeanitrimone ntoV dpa<mevlle.g net   11-.6.2 -,.. . ,	.L-ot'""t_(..,.il-know--n)----.-7-.".",E _x_p_ _d a_te_(<-.fknow-n-_,~ I2I  ~OO~tvvopeepsse  dOO ornn coo1o  ae00 re=d=uce',d'   
3. Oatttol  ....,_Uctlon  . 
event.  8. Event reappeared after
ln"'Idayyrl  o;.o 
5. Describe event or_ probiem  1-';;;2:;...--..;....._,..____......~....,.2::.-------,-1., Oves  O=n' 
9.. NDC I 2 lor product problems only (if known) 
120ves Ono.O=, 
tO. Concomitant meclical producta and 1~dales (exclude treatment pi ""'":"t) 
D.  Suspect medical device 
1 . Brand name 
2. Type ot device 
3. Manufecturer name & llddreas  4. 	Operator of device 
0 
health p<pt~ional
0 tay userlplltient . 
0 
o;her. 
:'' 
~--::------_..;,.------------15.
6 
model I 
7  II imptanted, give date 
 6. _Relevant tests/laboratory data. tneluding dates_  . tf"O'I:Say-)'fl  .
aerial I 
8. 	 II exptanted, give d!lte 
-loll    uno<lar''f"l 
9. Device available tor evaluation?  (Do nol send to FOAl 
0  yes  0  no  0  returned to ma~facturer on 
'"'""' 
10. Concomitant me<;tical products and therapy dates (exclude treatment of event) 
7. Other relevant history. including preexisting medical condi_tions (e.g .. al1erg.es. 
race. p<egnancy. smoktng and alcohol use. hepatic/renal dysfunction. etc.) 
E.  Initial reporter  .  - ' 
Heme, llddfess & phone  
Submission of a report does not constitute an  2. 	Health professional?  3.  Occupation  4  Initial reporter also 

admission that medical personnel, user facility,  Oves  Ono  Osevnte rse poOrt tnoo F DAD
 unk 
distributor, manufacturer or product caused or 
contributed to the event. 
FDA Fa<m 3500A (6193)  31614  Federal Register I V~l 58, No. 105 I Thursday. June 3, 1993 I  Notices 
Medication and Device  Submission of a report does not constitute
Experience Report  an admission that medical personnel, user
facility, distributor, manufacturer or product
(continued)  caused or contributed to the event. 
Refer to guidelines for specific instructions  Page  of 
H.  Device manufacturers only 
1. Type of repor1llble _. .  2. " follow.ilp, whal tYpe? ' 
0dealh  0  cooection  - '
0  0 
serious injury  additional information 

0  0 
malfunction (see guidelines) 
 response to FDA requesl 
0 
o~  device evalualion
3. Device evaluated by mfr? 
Onot 
n~~umedto""'.  

DyeS 0 SvaluatiOn summart atlaChed 1-:-"7"":'-:-~-:--:--~........_.;..~ 

Orio (anach page to explain why noll  5. labeled for single UM? 
0  0 
or prOVIde code:  yes  no 
I  I-I  I 
me4hod  1-1  1-1 
oesulls  I  1-1  1-1  H  J 
I  H  I 
concklsions  1-1  1-1 
7 Hremedial action nhlated,  8: Usage of device 
-c:lleck type 
0  0  0 tnlli31 use of d8~ -
recall  nottficatton 
0 
0 	 0 reuse 
rep8lf  _tnSpeclton 
Ounknown 
0  0 
replace  paltent monrtormg  9. 	 Haction reported to FDA under 
name/address .  0 	 relabeling 	 0 modtlicattonl  21 USC 3601(1), list correction/removal 
_-0  adjUSiment reportmg number: 
other 
0  0 
10.  Additional manufacturw narrative  and/or  11- Corrected data 
G.  All manufacturers - -- - .    
1. Contact olllce'-~(& mfriog sile.lor devices)  2 Phone number 
3. Report source 
(checl< all that apply) 
GJ 
foretgn 
0 
study 
, 0 
literature 
0 
consumer 
o
4. Date received by manulacturw  5.  proleSSional 
'""'"""'"  (A)NDAI  0  user taCi!tty 
INDI  0  company 
6. If IND. protocol  
represer:atat1ve 
PLA I 
0 
0  dtslnbutor 
pre-1938  yes  0 
7  Type of report other 
.  (check allhal apply)  OTC  Oves 
0  0  produd 
5-day  15-day 
8. Adversa eventterm(s) 
0  0 
10-day  periodiC 
0  0 
lnrtial  follow-up I 
9. Mfr. report number 
c......nc. 
TIW pubtfc ~bufOin few"* COIIKtion of~~hM belen estHMtM to .wr..,.,.....  Reports  ortteet. PHS  ~doNOT return this form 
;tmJoan: tofkw ln)fO.nf'~fh,l lhyOorun.t  ~6enoct~nlumdnenngt :Hs ~O:On-tiO.Nt .fMor ! N~d:ucm.g" tc"h'M-. b~ut.1 oMr~ n. nto'y:  .:_,= ~::4.4 '"--=c~=- ~WAT~T...,NP~"RVVAo4n . D~C 2~020w1 ~n1-e  to either of these addres~.
FDA Form 3SOOA beck 
(FR Doc. 93-12917 Filed 6-2-93; 8:45am) 
IJIUINQ COOl! 4110-0t-<: