QUALITY METRICS

TECHNICAL CONFORMANCE GUIDE

Technical Specifications Document

This Document is incorporated by reference into the following Guidance

Document(s):

Draft Guidance for Industry Request for Quality Metrics, published July 28,
2015

For questions regarding this technical specifications document, contact (CDER) Tara Gooen
Bizjak at 301-796-3257 or (CBER) Office of Communication, Outreach and Development at 1-
800-835-4709 or 240-402-8010.

U.S. Department of Health and Human Services

Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
 QUALITY METRICS
TECHNICAL CONFORMANCE GUIDE

Revision History

Date Version Summary of Revisions

June 2016 1.0 Initial version
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TABLE OF CONTENTS

TABLE OF CONTENTS ............................................................................................................. 3

1. INTRODUCTION............................................................................................................. 1
1.1 Background ....................................................................................................................... 1
1.2 Purpose............................................................................................................................... 1
1.3 Document Revision and Control ....................................................................................... 2
1.4 Relationship to Other Documents ..................................................................................... 2
2. EXCHANGE FORMAT – ELECTRONIC SUBMISSIONS ....................................... 2
2.1 File Transport Formats .................................................................................................... 2
2.1.1 Extensible Mark-up Language .................................................................................................. 2
3. FILE FORMAT – ELECTRONIC SUBMISSIONS ..................................................... 2
3.1 Variable and Dataset Descriptor Length .......................................................................... 2
3.2 Special Characters: Variables and Datasets ................................................................... 3
3.3 Variable and Dataset Names .............................................................................................. 3
3.4 Variable and Dataset Labels .............................................................................................. 3
3.5 Data Definition File ............................................................................................................. 3
4. GENERAL CONTENT AND FORMAT OF A SUBMISSION .......................................... 3
4.1 Data Element Specifications............................................................................................. 3
4.2 Data Elements - Descriptions ............................................................................................. 3
4.2.1 Drug Product Name ................................................................................................................... 3
4.2.2 Drug Designation ....................................................................................................................... 4
4.2.3 Applicable Monograph ............................................................................................................... 4
4.2.4 Drug Product Type ..................................................................................................................... 4
4.2.5 Applicant Name .......................................................................................................................... 4
4.2.6 Final Labeler Name ................................................................................................................... 4
4.2.7 Final Labeler Codes ................................................................................................................... 4
4.2.8 Application Type ......................................................................................................................... 4
4.2.9 Application Number ................................................................................................................... 4
4.2.10 NDC Product Code ................................................................................................................... 5
4.2.11 Time Period Start...................................................................................................................... 5
4.2.13 Lots Attempted .......................................................................................................................... 5
4.2.14 Lots Rejected ............................................................................................................................. 5
4.2.16 Out of Specification (OOS) Results – Finished Drug Product or API ............................... 5
4.2.17 Number of Lot Release and Stability Tests – Commercial Use .......................................... 5
4.2.18 Out of Specification (OOS) Results Invalidated ................................................................... 5
4.2.19 Product Quality Complaints ................................................................................................. 6
4.2.20 Lots Attempted and Released ............................................................................................... 6
4.2.21 Annual Product Review (APR) / Product Quality Review (PQR) Completed ..................... 6
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4.2.22 Annual Product Review (APR) / Product Quality Review (PQR) Required........................ 6
4.2.23 DUNS Number.......................................................................................................................... 6
4.2.24 Dosage Form ........................................................................................................................ 6
4.2.25 Facility Establishment Inventory Number (FEI) ................................................................. 6
4.2.26 Establishment Activity Classification ................................................................................... 6
4.3 Mandatory Data Elements – Formats ............................................................................... 6
4.4.1 APR Approval ............................................................................................................................. 8
4.4.3 Percentage of Corrective Actions and Preventive Actions (CAPA) Involving Re-training ..... 8
4.4.4 Process Capability (PC) or Process Performance (PP) Index Calculation .............................. 8
4.4.5 CAPA Trigger Policy .................................................................................................................. 8
4.4.6 Triggers for CAPA...................................................................................................................... 8
4.5 Optional Data Elements – Formats ................................................................................... 9
5.0 DATA VALIDATION RULES .............................................................................................. 9
6.0 GLOSSARY........................................................................................................................... 10
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QUALITY METRICS TECHNICAL CONFORMANCE GUIDE

This technical specifications document, when finalized, will represent the Food and Drug
Administration’s (FDA’s) current thinking on this topic. It does not create or confer any rights for
or on any person and does not operate to bind FDA or the public. You can use an alternative
approach if the approach satisfied the requirements of the applicable statutes and regulations. If
you want to discuss an alternative approach, contact the FDA staff responsible for implementing
this guidance. If you cannot identify the appropriate FDA staff, send an email to mailto:CDER-
[email protected].

1. INTRODUCTION
1.1 Background

This Quality Metrics Technical Conformance Guide (Guide) serves as the technical reference for
implementation of the draft FDA guidance for industry on Request for Quality Metrics. 1 Since
publication of the Pharmaceutical CGMPs for the 21st Century in 2004, 2 CDER has continued to
promote its vision of “a maximally efficient, agile, flexible manufacturing sector that reliably
produces high-quality drug products without extensive regulatory oversight.” The draft guidance
for industry on Request for Quality Metrics and this technical reference document continue
FDA’s policy efforts to ensure successful implementation of CDER’s objectives outlined in the
21st Century publication. FDA expects that quality metrics calculated from data that it collects
will provide objective measures that, when used with additional internal data, will provide the
Agency with indicators of the effectiveness of pharmaceutical manufacturing quality systems.
The goal of these measures is to assure quality drug products are available to patients. The
objectives of CDER’s quality metrics program can best be achieved through collaboration and a
shared understanding of standards for metric indicators and data exchange/reporting.

This Guide supplements the draft FDA guidance for industry on Request for Quality Metrics and
provides recommendations about submission of information that will support the FDA’s
calculation of quality metrics.

1.2 Purpose

This Guide provides technical recommendations for the submission of quality metric data. It is
intended to ensure clear expectations for industry on the submission of quality metric data as
described in the Request for Quality Metrics draft guidance.

1
See http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm455957.pdf.
We update guidances periodically. To make sure you have the most recent version of a guidance, check the FDA
Drugs guidance Web page at
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm310704.htm.
2
See Pharmaceutical cGMP’s for the 21st Century: A Risk- Based Approach at
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/Manufacturing/QuestionsandAnswersonCurrentGoodMan
ufacturingPracticescGMPforDrugs/ucm137175.htm.

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1.3 Document Revision and Control

This document is incorporated by reference into the draft FDA guidance for industry on Request
for Quality Metrics. Please refer to the draft guidance at
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
CM455957.pdf for ongoing changes to the guidance or submission processes before final
adoption.

1.4 Relationship to Other Documents

For resources on data standards, please also refer to the Study Data Technical Conformance
Guide located on the FDA Study Standards Resources Web page at
http://www.fda.gov/forindustry/datastandards/studydatastandards/default.htm.

2. EXCHANGE FORMAT – ELECTRONIC SUBMISSIONS

2.1 File Transport Format

Currently, FDA receives, processes, and archives electronic dataset files in several formats. The
FDA is committed to open dialog about best practices which includes a review of various
formats. Extensible Markup Language (XML) shall be the recommended format for Drug
Quality Metrics submission.

2.1.1 Extensible Mark-up Language

Extensible Mark-up Language (XML), as defined by the World Wide Web Consortium (W3C),
specifies a set of rules for encoding documents in a format that is both human-readable and
machine-readable. 3 XML’s primary purpose is to facilitate the sharing of structured data across
different information systems.

3. FILE FORMAT – ELECTRONIC SUBMISSIONS

3.1 Variable and Dataset Descriptor Length

The length of variable names, descriptive labels, and dataset labels should not exceed the
maximum permissible number of characters described in Table 1:

Table 1: Maximum Length of Variables and Dataset Elements

Element Maximum Length in Characters
Variable Name 8
Variable Descriptive Label 40
Dataset Label 40
3
See http://www.w3.org/XML.

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3.2 Special Characters: Variables and Datasets

Variable names, as well as variable and dataset labels, should include only American Standard
Code for Information Interchange (ASCII) text codes.

3.3 Variable and Dataset Names

Variable and dataset names should not contain punctuation, dashes, spaces, or other non-
alphanumeric symbols. In addition, the variable and dataset names should not contain special
characters, including:

\ / * ,? < > | “ ‘ : % # + ( ) { } [ ]

3.4 Variable and Dataset Labels

Variable and dataset labels can include punctuation characters. However, special characters
should not be used, such as:

1. Unbalanced apostrophe, e.g., Parkinson's.

2. Unbalanced single and double quotation marks.
3. Unbalanced parentheses, braces, or brackets, e.g., ‘(‘, ‘{‘and ‘[‘.
4. ‘<’ less than sign and ‘>’ greater than sign.

3.5 Data Definition File

The data definition file is a human and machine-readable dataset that contains a list of the
datasets included in the submission along with a detailed description (i.e., metadata) of the
contents of each data set.

4. GENERAL CONTENT AND FORMAT OF A SUBMISSION

4.1 Data Element Specifications

Below are product data elements which correlate to column product names described in
Appendix-A of the draft FDA guidance for industry on Request for Quality Metrics.

4.2 Data Elements - Descriptions

4.2.1 Drug Product Name

For drugs that are subject to approved applications under section 505 of the FD&C Act or under
section 351 of the PHS Act, and for drugs that are described in a drug master file (DMF) that is
intended to support an application, the API/drug substance or FDF/drug product name provided
in the application should be used.

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For drugs that are not subject to an approved application under section 505 of the FD&C Act or
under section 351 of the PHS Act, the API or FDF drug product name should be used. If the drug
product name is included as part of registration, the same name included in registration should be
used.

4.2.2 Drug Designation

Indicate if the drug referenced in the completed data table is prescription (Rx) or over-the-
counter (OTC). This element is not required to be reported for an API intended for use in the
manufacture of a drug product.

4.2.3 Applicable Monograph

The applicable monograph, if any, for the drug referenced. This element is not required to be
reported for products that are subject to an application under either section 505 of the FD&C Act
or under section 351 of the PHS Act, or covered by a submission to a DMF that is intended to
support such an application.

4.2.4 Drug Product Type

The drug product type – Active Pharmaceutical Ingredient (API) or Finished Dosage Form
(FDF). This field is restricted to two options; only one option can be selected.

4.2.5 Applicant Name

The name of the application holder.

4.2.6 Final Labeler Name

The name of the labeler listed in the NDC code.

4.2.7 Final Labeler Codes

The name of the labeler listed in the NDC code (for validation of text entered as “final labeler
name”).

4.2.8 Application Type

The application type is New Drug Application (NDA), Abbreviated NDA (ANDA), Biologics
License Application (BLA), Drug Master File (DMF), or Non-application product (NA).

4.2.9 Application Number

The NDA, ANDA, BLA number for an approved product or the applicable DMF number. Leave
blank for non-application products.

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4.2.10 NDC Product Code

The final labeled NDC product code.

4.2.11 Time Period Start

The beginning of the time period within which the data being reported were collected.

4.2.12 Time Period End

The end of the time period within which the data being reported were collected.

4.2.13 Lots Attempted

The number of lots attempted for the drug referenced above in 4.2.1 for each establishment. 4

4.2.14 Lots Rejected

The number of specification-related lots rejected for the drug referenced above in 4.2.1 for each
establishment.

4.2.15 Attempted Lots Pending Disposition

The number of lots attempted pending disposition for more than 30 days on the last day of the
time period within which the data being reported was collected.

4.2.16 Out of Specification (OOS) Results – Finished Drug Product or API

The number of test results that fall outside the specifications or acceptance criteria for the drug
referenced above in 4.2.1 for each establishment.

4.2.17 Number of Lot Release and Stability Tests – Commercial Use

The number of lot release and stability tests conducted for the drug referenced above in 4.2.1 for
each establishment.

4.2.18 Out of Specification (OOS) Results Invalidated

The number of invalidated OOS results for finished drug product or API and stability tests due to
laboratory error for the drug referenced above in 4.2.1 for each establishment.

4
In this section of the guidance, “establishment” means “covered establishment” as defined in the FDA guidance for
industry on Request for Quality Metrics.

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4.2.19 Product Quality Complaints

The sum of product quality complaints received for product distributed in the United States for
the drug product referenced above in 4.2.1 across all establishments.

4.2.20 Lots Attempted and Released

The number of lots attempted which are released for distribution or for the next stage of
manufacturing for the finished drug product or API referenced above in 4.2.1 for each
establishment.

4.2.21 Annual Product Review (APR) / Product Quality Review (PQR) Completed

Indication (yes/no) of whether the APR or PQR was performed within 30 days of the annual due
date.

4.2.22 Annual Product Review (APR) / Product Quality Review (PQR) Required

Number of APRs or PQRs required.

4.2.23 DUNS Number

The DUNS number for each establishment listed in the quality metrics data submission.

4.2.24 Dosage Form

The dosage form for the drug product referenced above in 4.2.1.

4.2.25 Facility Establishment Inventory Number (FEI)

The FEI for each establishment listed in the quality metrics data submission.

4.2.26 Establishment Activity Classification

List the activity classification (e.g., Direct Product Manufacturing) for all establishments listed in
the quality metrics data submission.

4.3 Mandatory Data Elements – Formats

Table 2: Mandatory Data Element Formats

Data Element Data Element Data Data Element Description
Name Label Element
Type
PRODNAME Drug Product Name Text
RXSTATUS RX OTC Status Text RXSTATUS = RX or OTC

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Data Element Data Element Data Data Element Description

Name Label Element
Type
Applicable
MONOGRPH Text
Monograph
PRODTYPE Drug Product Type Text PRODTYPE = API, FDF
APPLICNT Applicant Name Text
FINLBLER Final Labeler Name Text
LABELER Final Labeler Codes Num
APPTYPE = NDA, ANDA, BLA
APPLTYPE Application Type Text
DMF, or NA
APPNUM Application Number Text
NDCCODE NDC Product Code Num
TIMEPRD Time Period Start Date
TIMEPRD Time Period End Date
Number of lots attempted of the
LTSATT Lots Attempted Num
product
Number of specification-related
LTSREJ Lots Rejected Num
rejected lots of the product
Number of attempted lots pending
APRWIDD Attempted Lots Num
disposition (more than 30 days)
Out-of-Specification Number of OOS results - Finished
OOSRES Num
Results product (including stability testing)
Number of lot release tests
LTRELTST Lot Release Tests Num
conducted for commercial use
Number of OOS results for finished
Out-of-Specification product and stability tests for the
OOSRESIN Num
Results Invalidated product that are invalidated due to
lab error
Number of product quality
Product Quality
PRODQCMP Num complaints received for the product
Complaints
distributed in the United States
Number of lots attempted that are
Lots Attempted and released for distribution or for the
LTSREL Num
Released next stage of manufacturing the
product
Have associated APRs or PQRs
APR/PQR been completed within 30 days of
APRWIDD Text
Completed annual due date for the product?
APRWIDD = Y or N
APR or PQR Number of APRs or PQRs required
APRPQRS Num
Required for the product
A unique nine-digit identification
DUNSNUM DUNS Number Num
number for each physical facility

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Data Element Data Element Data Data Element Description

Name Label Element
Type
location
DOSAGE Associated finished dosage form
Dosage Form Text
FORMS
Facility
Facility Establishment Inventory
FEINUM Establishment Num
Number
Inventory Number
Subset of Business Operations:
Establishment
ACTIVITY Text Analytical testing, Pack,
Activity
Manufacture, Other
QUARTER Reporting Quarter Text QUARTER= 1, 2, 3, or 4

4.4 Optional Data Elements - Descriptions

4.4.1 APR Approval

Indicate Yes/No to indicate whether each associated APR/PQR was reviewed and approved.

4.4.2 APR Approval by Quality Unit and/or Operations Unit

If response to 4.4.1 is Y, indicate whether the approving entity was: 1. Head of the quality unit;
2. Head of the operations unit; 3. Both; or 4. Other.

4.4.3 Percentage of Corrective Actions and Preventive Actions (CAPA) Involving Re-
training

Indicate the estimated percentage of your corrective actions plans that involved re-training of
personnel (i.e., a root cause of the deviation is lack of adequate training).

4.4.4 Process Capability (PC) or Process Performance (PP) Index Calculation

Indicate Yes/No if PC or PP Index was calculated for each critical quality attribute as part of that
product’s APR or PQR.

4.4.5 CAPA Trigger Policy

Indicate Yes/No if establishment management has a policy requiring CAPA at some lower
process capability or performance index.

4.4.6 Triggers for CAPA

Related to 4.4.5, indicate what PC or PP index value triggers a CAPA.

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4.5 Optional Data Elements – Formats

Table 3: Optional Data Element Formats

Data Element Data Element Data Data Element Description

Name Label Element
Type
Was each APR/PQR reviewed and
APRAPPVD APR/PQR Approved Text approved?
APRAPPVD = Y or N
APR/PQR Approved 1. Head of the quality unit; 2. Head
Text
APRAPPVDY by Quality and/or of the operations unit; 3. Both; or 4.
Operations Unit Other.
CAPAs Requiring What percentage of CAPA required
CAIRTP NUM
Re-Training re-training of personnel?
Is a PC or PP Index calculated for all
PC/PP Index
PCPPCALC Text CQA?
Calculation
PCPICALC = Y or N
Are CAPAs triggered at some lower
CAPA Trigger
REQCAPA Text PC or PP Index?
Policy
REQCAPA = Y or N
What PC or PP index value triggers
PCPPCAPA Triggers for CAPA Num
a CAPA?

5.0 DATA VALIDATION RULES

For purposes of this Guide, data validation is a process that attempts to ensure that submitted
data are both compliant and useful. Compliant means the data conform to the applicable and
required data standards. Useful means that the data support the intended use (i.e., regulatory
review and analysis). Data validation is one method used to assess submission data quality.
Standardized data do not ensure quality data, but they do make it easier to assess some aspects of
data quality by facilitating the automation of various data checks. Data validation relies on a set
of validation rules that are used to verify that the data conform to a minimum set of quality
standards. The data validation process can identify data issues early in the review that may
adversely affect the use of the data. FDA recognizes that it is impossible or impractical to define
a priori all the relevant validation rules for any given submission. Sometimes serious issues in
the submitted data are only evident through manual inspection of the data and may only become
evident once the review is well under way. Often these issues are due to problems in data content
(i.e., what was or was not submitted, or issues with the collection of original source data), and
not necessarily how the data were standardized.

When the FDA guidance for industry on Request for Quality Metrics is published in final, the
validation rules will be posted to the external FDA Web page. Establishments should validate
their metric data before submission using the posted validation rules and correct any validation
errors.

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6.0 Glossary
The following is a list of acronyms and terms used in this technical specifications document:

API: Active Pharmaceutical Ingredient

APR: Annual Product Review
ASCII: American Standard Code for Information Interchange
BLA: Biologics License Application
CAPA: Corrective Action and Preventive Action
CBER: Center for Biologics Evaluation and Research
CDER: Center for Drug Evaluation and Research
DMF: Drug Master File
DUNS: Data Universal Numbering System
ESG: Electronic Submissions Gateway
FD&C Act: Federal Food, Drug, and Cosmetic Act
FDF: Finished Dosage Form
FEI: Facility Establishment Identifier Number
NDA: New Drug Application
NDC: National Drug Code
OOS: Out-of-Specification
OPQ: Office of Pharmaceutical Quality
OTC: Over the Counter
PQR: Product Quality Review
PQS: Pharmaceutical Quality System
Rx: Prescription
W3C: World Wide Web Consortium
XML: Extensible Markup Language

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