0800 GFI Outsourcing registration and reporting of drugs DEC 2016

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 FDA’s 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/GuidanceComplianceRegulatoryInformat ion/Gu idances/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 FDA’s electronic
submission system, and supersedes FDA’s 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 assigned 9

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 FDA’s 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
Product, If
Assigned
(Use FDA 10
digit format
with hyphens)

Active
Ingredient(s)
(Enter each
ingredient on a
separate line
directly
beneath)

Strength of
Active
Ingredient in
Final Product

Dosage Form

Route of
Administration

10%

Source NDC
for Active
Ingredient
(Separate
multiple
source NDCs
for the same
active
ingredient with
a semicolon
";")
23456-789-90

12345-678-90

Hydrocortisone

12345-679-91
12345-679-92

Hydrocortisone
Hydrocortisone

Package
description

Number of
units produced
between
12/1/14 and
5/31/15
(integers only)

Cream

T opical

20oz jar

1000

5%
5%

34567-8901-2
34567-8901-2

Cream
Cream

T opical
T opical

40oz jar
20oz jar

1500
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