Electronic   Drug  Product Reporting   for  

Human Drug  Compounding  Outsourcing 
 
Facilities  Under  Section  503B of  the  

Federal  Food,  Drug,  and  Cosmetic  Act 
 
 
Guidance  for Industry  

 
 
 
 
 
 
 
 
 
 
U.S. Department  of Health  and  Human  Services
  
Food and Drug  Administration  

Center  for  Drug Evaluation  and  Research  (CDER) 
 
Office  of Compliance 
 
 
 
 
December 2016 

Compounding   and Related Documents 
 
   
 
Electronic   Drug  Product Reporting   for  

Human Drug  Compounding  Outsourcing 
 
Facilities  Under  Section  503B of  the  

Federal  Food,  Drug,  and  Cosmetic Act  

 
Guidance  for Industry  

 
 
 
 
Additional  copies are available  from: 

Office of Communications, Division of Drug Information 

Center  for Drug Evaluation and Research 

Food and Drug Administration 

10001 New Hampshire Ave. Hillandale Bldg., 4th Floor
  
Silver Spring, MD 20993 

Phone: 855-543-3784 or 301-796-3400; Fax: 301-847-8714 

Email:  druginfo@fda.hhs.gov
  
http //www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm  
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department  of Health  and  Human  Services
  
Food and Drug  Administration  

Center  for  Drug Evaluation  and  Research  (CDER) 
 
Office  of Compliance 
 
 
December 2016 

Compounding   and Related Documents 
 
 
   
 
 
TABLE OF CONTENTS
  
 
I.   INTRODUCTION............................................................................................................. 1 
 
II.   BACKGROUND  ............................................................................................................... 1 
 
III.   SCOPE  OF THIS GUIDANCE  ....................................................................................... 2 
 
IV.   SUBMITTING  COMPOUNDED PRODUCT REPORTS  ........................................... 2 
 
A.   Who Must Report and What Must They Report.................................................................. 2
  
B.   When to Report ...................................................................................................................  3
  
C.   How to Report  .....................................................................................................................  3
  
D.   Confidentiality of Reporting Information ............................................................................ 5
  
 
 
   
 
Guidance  for Industry  

Electronic Drug  Product  Reporting for  Human Drug Compounding 
 
Outsourcing  Facilities  Under  Section 503B of the Federal  Food, 
 
Drug,  and  Cosmetic Act 
 
 
 
I.   INTRODUCTION  
 
This  guidance   explains   how  facilities   that elect  to  register  with  FDA  as  outsourcing   facilities   are  
to  submit   drug product reports, consistent   with section  503B of  the  Food, Drug, and  Cosmetic  
Act  (FD&C  Act)  (21 U.S.C. 353b).1   Section  503B  of  the  FD&C  Act provides  that a  facility   that 
elects  to  register  with  FDA  as  an  outsourcing   facility   must  report  to FDA  certain  information  
about the  drugs  compounded  at  that outsourcing   facility   in the form  and  manner   that FDA may  
prescribe  by  regulation   or guidance.2    This  guidance   describes  who must  report  and what 
information   they  must  provide  and  explains   that  drug  compounding   reports  must  be submitted   in  
structured product labeling  (SPL) format  using   FDAs  electronic   submissions   system.   
 
Because  Congress  gave FDA  explicit   statutory authority   to establish   binding   requirements   in  
guidance   as  to  the  form  and  manner  in  which  reports  are  to  be  prepared, those portions  of  this  
guidance   relating   to such  form  and  manner   are  not  subject to  the  usual  restrictions   in FDA's good  
guidance   practices  (GGP)  regulations   (i.e., the  requirements   that  guidances   not  establish   legally  
enforceable   responsibilities   and  that  guidances   prominently   display  a  statement   of  the  
document's nonbinding   effect).3    
 
II.   BACKGROUND  
 
The  DQSA added  new  section  503B  to the  FD&C  Act.  Under section  503B(b), a compounder  
can  elect  to  become an  outsourcing   facility   by  registering   with  FDA  and  meeting   the  other  
requirements   described in section  503B  of the  FD&C  Act.4   Outsourcing   facilities   are  inspected  
by  FDA on  a risk-based schedule   and  must  comply with other  provisions   of  the  FD&C  Act,  such  
as current  good  manufacturing   practice  (CGMP)  requirements.    Details   on  other requirements  
applicable   to  outsourcing   facilities   are  the subject of separate  guidance   documents.5  
A  facility   that  elects  to  become  an  outsourcing   facility  must, at the  time  of  initial   registration   and  
twice  each  year, in June and  December, submit   to  FDA  a  report  identifying  the  drugs  
                                                 
1  Section  503B  was added  to the FD&C  Act by  the Drug  Quality  and Security  Act  (DQSA),  Pub. Law  No. 113-54,  
on November  27,  2013.  
2  See  section 503B(b)(2)(B).  
3  See  21 CFR 10.115(d)   &  (i).  
4  See  the guidance for  industry  Registration for  Human  Drug  Compounding Outsourcing Facilities under Section  
503B of  the FD&C Act.  
5 All FDA guidances are available on the FDA guidance web page. FDA updates guidances regularly.   To make sure  
you have the most  recent version of a guidance, always consult the guidance web  page at  
http://www fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default htm.    
  1    
 
compounded  by  the  facility   during  the  previous   six-month  period.6  For each  identified   drug,  the  
outsourcing   facility   must  provide  certain   information,   which   is  listed   in section  
503B(b)(2)(A)(ii).     
 
III.    SCOPE OF THIS  GUIDANCE  
 
This  guidance   addresses the  provisions   in the DQSA  regarding   the  drug  reporting  requirements  
for registered   outsourcing   facilities.   Separate guidance   documents   provide  instructions   on  which  
facilities   should   register   with FDA  as  outsourcing   facilities   and how  to do so.  FDA  has  modified  
its electronic   submission   system  to  accept  the electronic   reports  for drugs compounded   by  
registered   outsourcing   facilities   in  SPL  format. This  guidance   provides  instructions   for  
outsourcing  facilities   to report  compounded  drugs  in SPL  format  using   FDAs electronic  
submission   system, and supersedes FDAs draft guidance,  Interim Product  Reporting for Human 
Drug Compounding Outsourcing Facilities  Under Section 503B  of  the FD&C Act.  
 
IV.   SUBMITTING  COMPOUNDED PRODUCT REPORTS  
 
A.  Who  Must Report  and What  Must They  Report  
 
Upon  initial   registration   as  an  outsourcing   facility   under  section  503B  and  twice  each  year  (in  
June  and  December),   each  registrant   must  submit   a  drug  product  report  to FDA.7   This  means  
that even if  the outsourcing   facility   has not  compounded   any drug products  during  the previous  
six-month  period, it must submit a  report to  FDA  indicating   that it has not  compounded   any  drug  
products  during  the  period.  
 
This  report must  identify   all  sterile  and  non-sterile   drugs  compounded  at  the outsourcing   facility  
during   the  previous   six-month  period  and  provide  all  of  the  following  information   for  each  
compounded  drug8:  
 
	   The  active  ingredient   and  strength   of  active  ingredient   per  unit  
	   The source of  the active  ingredient   
	   The National  Drug  Code  (NDC)  number  of  the source drug or  bulk  active  ingredient,   if  
available  
	   The  dosage  form  and route  of administration  
	   The package  description  
	   The  number  of  individual  units produced  
	   The NDC number  of the final  product, if assigned9   
 
For purposes  of  drug  product  reporting  under  section  503B(b), the  strength of  the active  
ingredient  per unit  is  the  strength  of  the  active  ingredient   per dose  of  the  product.   
                                                 
6  Section 503B(b)(2)   of the FD&C  Act.  
7  Section  503B(b)(2)(A)  of the FD&C  Act.  
8  Section  503B(b)(2)(A)  of the FD&C  Act.  
 
9  Section 503B(b)(2)(A)(ii)   of the FD&C  Act.  
  2    
 
 
 
The  NDC number  for  both  the  source  drug  or bulk active  ingredient   and any finished   drug  
product to  which  an NDC  has been  assigned   must  be submitted   in  the  standard  format  of 
ten numerical   digits  with dashes separating   the three segments, for example, in a 5-4-1, 5-3-2, or  
4-4-2 configuration.   
 
The  package  description  refers  to the  description  of  the  smallest   individual  saleable  package  of  
the product  for distribution  and must  include   the  type  of  package  (e.g., vial, syringe,  bottle)  and  
the  volume   per package  (e.g.,  100 ml  vial,   5 ml  syringe,  100 tablets  per  bottle).   
 
The  number of  individual  units produced  refers  to  the  number  of  the  smallest   individual   saleable  
packages  of  product for distribution.   For  example,  if  a registered outsourcing   facility  
compounds  one  thousand  100 ml  vials  of  5 mg/ml  of  Drug  X, the  strength of  the active  
ingredient  per unit  is  5  mg/ml,  the  package description  is  100  ml  vials,  and  the  number of  
individual  units produced  is  1,000 vials.   Similarly,   if  a registered  outsourcing   facility  
compounds  5 mg  tablets  of  Drug  Y  in  one  thousand  bottles  of  100 tablets  each, the  strength of  
the active  ingredient  per unit  is  5 mg,  the  package  description  is  bottles  of  100 tablets,  and  
the  number  of  individual  units produced  is  1,000 bottles.  
 
B.   When to Report  
 
Registered  outsourcing   facilities   must  submit   a  report  upon  initial   registration   under  section  
503B  of  the  FD&C  Act  and  twice  each  year  thereafter, once  in  June and  once in December.10   
Initial   drug  product  reports  must  identify   products  compounded  during the  previous six  month  
period,  not  including   the  month  in  which  the  facility   registers.   Semiannual   drug  product reports  
submitted   between  June  1 and  June  30 of  each  year  must  report  products  produced during  the  
previous  six  month   period from  December  1  through  May  31.  Semiannual   reports submitted 
between  December  1 and  December  31 of  each  year  must  report  drug  products  compounded 
during   the  previous  six  month  period from  June 1 through   November  30.11    
 
C.  How  to Report  
  
Section  503B(b)(3)  of  the  FD&C  Act  requires  outsourcing  facilities   to submit   drug  reporting  
information   by  electronic   means, unless  FDA  grants  a  request for a  waiver  of such requirement  
because  use  of  electronic   means is not reasonable  for  the  person  requesting   the  waiver.    FDA 
has  modified   its  electronic   submission   system  to  accept  electronic   submissions   in  SPL  format  for  
drugs  compounded by  registered  outsourcing   facilities.    Therefore, a facility   that elects  to  
register  with  FDA as  an  outsourcing   facility   must  submit   drug  product reporting   information  
using   FDAs  electronic  reporting   system  and  the  SPL  format,  unless  FDA  has  granted  the  facility  
a waiver.    
 
FDA  has  created  a  new  SPL  document  type  category  for  outsourcing   facilities   drug  product  
report  submissions.   Outsourcing   facilities   making   electronic   submissions   must  submit   drug  
                                                 
 
11  Section  503B(b)(2)(A)  of the FD&C  Act.  
  3    
 
product  reporting   information   using   the  document   type  Human   Compounded  Drug  Label.12   
Section  IV  of  the  guidance   for  industry   Providing Regulatory  Submissions  in Electronic  Format  
  Drug Establishment  Registration and Drug Listing  provides  detailed instructions   on  how  to 
submit   information   using   SPL.  FDA  also offers  tools and  information   for creating   and  
submitting   SPL files.    Additional   information   can  be found at  www.fda.gov/edrls.   
 
Although  each  compounded product  could be  reported in  a  separate  SPL  submission,  techniques  
can  be used  to simplify   and combine   the  submissions   for  products  with  identical  active  
ingredients,  different   packaging   presentations,  formulations,  and/or  strengths.    Multiple  
strengths,   package  sizes,  and  source  NDC  numbers  can  be  reflected  in  a  single   SPL  submission, 
which  will   reduce  the  number  of  SPL  submissions   that  a  facility   will   need  to submit  to FDA.   
For example, the  following  table  contains   data that  could be consolidated  into a single   product  
SPL  submission:  
 
NDC of Final  Active  Strength of   Source NDC   Dosage Form   Route of   Package   Number of 
Product, If  Ingredient(s)   Active  for Active   Administration   description   units produced 
Assigned   (Enter each   Ingredient in  Ingredient   between  
(Use FDA 10   ingredient on a   Final Product   (Separate  12/1/14 and  
digit format   separate line   multiple   5/31/15  
with hyphens)   directly   source NDCs   (integers only)  
beneath)   for the same 
active  
ingredient with  
a semicolon  
";")  
12345-678-90   Hydrocortisone   10%   23456-789-90   Cream   T opical   20oz jar   1000  
   
12345-679-91   Hydrocortisone   5%   34567-8901-2   Cream   T opical   40oz jar   1500  
12345-679-92   Hydrocortisone   5%   34567-8901-2   Cream   T opical   20oz jar   1200  
 
Furthermore,   SPL  submissions   can  be  saved,  updated, and resubmitted  for  subsequent  reporting  
periods  instead  of  creating  a new  submission   each time.  In  addition,  any product that is  not  
compounded in  a particular   6 month  period  does  not require  an  SPL  submission,   even  if  the  
outsourcing   facility   sent in a  submission   for that product previously.  
 
Whether  the  product  report  is  for  initial  registration  or  the  semiannual  reporting  period, if an  
outsourcing   facility   has  not  compounded  any  products for  the previous  six  month  period, a  report  
explicitly   stating   so  must  be submitted.13   This  can  be  accomplished   by  creating   a  single   Human  
Drug  Compounded Drug  Label  SPL  file  and indicating  No Products to  Report in  the  data  
elements  section.  
 
FDA  does  not  anticipate   many  instances  in  which  electronic   submission   of  reporting   information  
will  not  be reasonable  for  a facility   because  the  electronic   system  for  submitting   the  information  
is  an  internet-based system accessible to  all  facilities   seeking  to  register.  It  is  likely   to be easier  
                                                 
12 The SPL  document type name Human  Compounded Drug Label was chosen by the FDA Data Standards  
Council  to  distinguish  drug product  reporting submissions  under section  503B  from  drug registration and listing  
submissions under section 510.  
 
13  Section 503B(b)(2)(A).  
  4    
 
to report product information  electronically  than  in paper  form.   However,  to apply  for  a waiver  
from  the  requirement  to  electronically   submit  drug  reporting   information,   please provide  a  
written  request with  a complete  explanation   of why the use  of  electronic   means  is  not  reasonable  
to the  following:  
 
Drug  Registration   and  Listing   System  Staff  
U.S. Food and Drug Administration 
 
10903 New Hampshire   Avenue
  
Silver Spring, MD  20993
  
 
or   
  
Email:   edrls@fda.hhs.gov  
 
If you are  granted  a  waiver,  you will   be  instructed   on  how to  submit   product reporting  
information.     
 
D.  Confidentiality  of  Reporting Information  
 
Section  503B(b)(1)(B)(i)   provides  that  outsourcing  facility  registrations   are  available   for  
inspection   to any  person  so requesting.  
 
Section  503B(b)(2)(C) specifies   that  product  reports  are  exempt  from  inspection   under  section  
503B(b)(1)(B)(i)   unless  the Secretary finds   that such an  exemption   would  be  inconsistent   with  
the protection  of the  public  health.   FDA finds   that exempting  from  disclosure   some of  the  
information  submitted  in product reports would be  inconsistent   with  the  protection  of  the public  
health, specifically,   for each  marketed product:  the  name  of  the  outsourcing   facility,   address  of  
the  outsourcing   facility,   name  of  the  active  ingredient,   strength   of  the  active  ingredient   per  unit,  
dosage  form, package  description,  and NDC  of  the  final  product  (if  assigned).   This  information  
is  generally   required  on  product  labels  or  publicly   available,   but  publication   of  this  information  
will   facilitate   product  recalls  when  they  are  necessary,  and  assist the public  in finding  
outsourcing   facilities   that have  compounded  certain  drug  products,  particularly   drugs  in shortage.  
FDA intends to  publish   this  information   on  our  Web site. FDA  does  not  intend to publish  
information   about  a  drug  submitted   in a  product report  if  an  outsourcing   facility   notes in the  
report  that it has  not distributed   the drug and  has not  advised  any person of  its intent   or  ability   to  
compound  the  drug.  
 
  
 
 
 
 
  5