Standards Development and the Use of 
Standards in Regulatory Submissions 
Reviewed in the Center for Biologics 
Evaluation and Research 
 
 
Guidance for Industry 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Additional copies of this guidance are available from the Office of Communication, Outreach 
and Development (OCOD), 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, 
MD 20993-0002, or by calling 1-800-835-4709 or 240-402-8010 or email at ocod@fda.hhs.gov, 
or from the Internet at 
https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guid
ances/default.htm. 
 
For questions on the content of this guidance, contact OCOD at the phone numbers or email 
address listed above. 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Biologics Evaluation and Research 
March 2019  Contains Nonbinding Recommendations 
 
Table of Contents 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 1 
III.  DISCUSSION .................................................................................................................... 2 
A.  What Is a Standard? ............................................................................................. 2 
B.  How Do Standards Differ from Regulations? .................................................... 2 
C.  What Is a Standards Development Organization (SDO)? ................................ 2 
D.  What Is a Voluntary Consensus Standards Body? ............................................ 3 
E.  What Are Voluntary Consensus Standards? ..................................................... 3 
F.  What Are Written or Documentary Standards? ............................................... 4 
G.  What Are Reference Materials or Physical Standards? ................................... 4 
H.  What Are Data Standards? .................................................................................. 4 
I.  What Are Performance Standards? .................................................................... 4 
IV.  HOW ARE VOLUNTARY STANDARDS DEVELOPED? ......................................... 4 
V.  WHAT ARE THE BENEFITS OF USING VOLUNTARY STANDARDS? .............. 5 
VI.  WHAT IS CBERS POLICY ON ACCEPTING STANDARDS USED IN 
REGULATORY SUBMISSIONS?.................................................................................. 5 
A.  What Is CBERs Policy on Use of Standards in Regulatory Submissions? .... 5 
B.  What if a Product Is Regulated by CBER as a Device? .................................... 8 
C.  Does CBER Take Accreditation Standards into Consideration when 
Assessing Compliance with CBER Regulatory Requirements? ....................... 8 
D.  Can Standards Developed by the World Health Organization (WHO) Be 
Used to Support a CBER Regulatory Submission? ........................................... 9 
VII.  REFERENCES ................................................................................................................ 10 
i  Contains Nonbinding Recommendations 
 
Standards Development and the Use of Standards in Regulatory 
Submissions Reviewed in the Center for Biologics Evaluation and 
Research 
 
 
Guidance for Industry 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or 
Agency) on this topic.  It does not establish any rights for any person and is not binding on FDA 
or the public.  You can use an alternative approach if it satisfies the requirements of the 
applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff 
responsible for this guidance as listed on the title page. 
 
 
I.  INTRODUCTION 
 
The purpose of this guidance is to describe the recommendations of the Center for Biologics 
Evaluation and Research (CBER) on the use of standards in product development and control as 
well as the use of such standards in CBERs managed review process.  CBER recognizes the 
value of standards and encourages the use of appropriate standards in the development and 
control of CBER-regulated medical products.  Sponsors use of standards can facilitate product 
development and provide a more efficient evaluation of regulatory submissions, including 
investigational new drug applications (INDs), biologics license applications (BLAs), new drug 
applications (NDAs), investigational device exemptions (IDEs), premarket approval 
applications, and premarket notifications, supplements, and amendments.  This guidance does 
not endorse the activities of specific Standards Development Organizations (SDOs) or 
recommend specific standards for use in regulatory submissions.  This guidance finalizes the 
draft guidance of the same title dated December 2017.   
 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the FDAs current thinking on a topic and should be 
viewed only as recommendations unless specific regulatory or statutory requirements are cited.  
The use of the word should in FDAs guidance means that something is suggested or 
recommended but not required. 
 
 
II.  BACKGROUND 
 
The Federal Governments policies on the use of voluntary consensus standards are described in 
the Office of Management and Budget (OMB) Circular A-119, Federal Participation in the 
Development and Use of Voluntary Consensus Standards and in Conformity Assessment 
Activities (Ref. 1).  The policies outlined in Circular A-119 were codified in the National 
Technology Transfer and Advancement Act of 1995 (NTTAA) (Ref. 2). 
 
1  Contains Nonbinding Recommendations 
 
The NTTAA authorizes the National Institute of Standards and Technology (NIST) to coordinate 
standards activities for federal agencies.  Neither CBERs use of nor CBERs acceptance of 
sponsors use of voluntary consensus standards constitutes a delegation of CBERs regulatory 
responsibilities.  Whether or not standards are used, CBER retains both the ability to set and the 
responsibility for setting appropriate regulatory criteria for CBER-regulated products. 
 
 
III.  DISCUSSION 
 
A.  What Is a Standard?  
 
For purpose of this guidance and as set forth in Circular A-119, the term standard (or 
technical standard) includes all of the following: (1) common and repeated use of rules, 
conditions, guidelines or characteristics for products or related processes and production 
methods, and related management systems practices; (2) the definition of terms; 
classification of components; delineation of procedures; specification of dimensions, 
materials, performance, designs, or operations; measurement of quality and quantity in 
describing materials, processes, products, systems, services, or practices; test methods 
and sampling procedures; formats for information and communication exchange; or 
descriptions of fit and measurements of size or strength; and (3) terminology, symbols, 
packaging, marking or labeling requirements as they apply to a product, process, or 
production method (Ref. 1). 
 
B.  How Do Standards Differ from Regulations? 
 
Federal regulatory agencies, such as FDA, are authorized by Congress to promulgate 
regulations to interpret and/or enforce legislation enacted by Congress.  Regulations have 
the force and effect of law and are generally mandatory, setting out specific requirements 
that regulated products and entities must meet. 
 
Standards are frequently developed outside of the federal government by an SDO.  The 
use of a standard is voluntary unless mandated by regulation or statute. 
 
C.  What Is a Standards Development Organization (SDO)? 
 
For purpose of this guidance, an SDO is an entity that develops or sponsors the 
development of voluntary standards for use or information by any person involved in the 
manufacture, distribution, sale, or use of products or services or the legal regulation of 
such products or services.  This definition includes but is not limited to voluntary 
consensus standards bodies (Ref. 3).  Additional information on SDOs can be obtained 
from NIST at https://www.nist.gov/ and the American National Standards Institute at  
https://www.standardsportal.org/usa_en/resources/sdo.aspx. 
 
 
 
2  Contains Nonbinding Recommendations 
 
D.  What Is a Voluntary Consensus Standards Body? 
 
A voluntary consensus standards body is one kind of SDO.  For purpose of this guidance 
and as set forth in Circular A-119, it is a type of association, organization, or technical 
society that plans, develops, establishes, or coordinates voluntary consensus standards, 
using a voluntary consensus standards development process that includes the following 
attributes or elements: 
 
1.  Openness:  The procedures or processes used are open to interested 
parties.  Such parties are provided meaningful opportunities to participate 
in standards development on a non-discriminatory basis.  The procedures 
or processes for participating in standards development and for developing 
the standard are transparent. 
 
2.  Balance:  The standards development process should be balanced. 
Specifically, there should be meaningful involvement from a broad range 
of parties, with no single interest dominating the decision-making. 
 
3.  Due Process:  Due process shall include documented and publicly 
available policies and procedures, adequate notice of meetings and 
standards development, sufficient time to review drafts and prepare views 
and objections, access to views and objections of other participants, and a 
fair and impartial process for resolving conflicting views. 
 
4.  Appeals Process:  An appeals process shall be available for the impartial 
handling of procedural appeals. 
 
5.  Consensus:  Consensus is defined as general agreement but not necessarily 
unanimity.  During the development of consensus, comments and 
objections are considered, using fair, impartial, open, and transparent 
processes (Ref. 1). 
 
Circular A-119 also explains that voluntary consensus standards bodies often have 
intellectual property rights (IPR) policies that include provisions requiring that owners of 
patented technology incorporated into a standard make that intellectual property available 
to implementers of the standard on nondiscriminatory and royalty-free or reasonable 
royalty terms (and binding subsequent owners of standards-essential patents to the same 
terms) (Ref. 1). 
 
E.  What Are Voluntary Consensus Standards? 
 
For purpose of this guidance, voluntary consensus standards are standards developed or 
adopted by a domestic or international voluntary consensus standards body. 
 
In order to qualify as a voluntary consensus standard for the purpose of Circular A-119, a 
standard that includes patented technology needs to be governed by intellectual property 
3  Contains Nonbinding Recommendations 
 
rights policies, as described in section III.D. of this guidance, put into place by the 
voluntary consensus standards body.  Circular A-119 states that such policies should be 
easily accessible, set out clear rules governing the disclosure and licensing of the relevant 
intellectual property, and take into account the interests of all stakeholders, including the 
IPR holders and those seeking to implement the standard (Ref. 1). 
 
F.  What Are Written or Documentary Standards? 
 
For purpose of this guidance, written or documentary standards include documents that 
set forth performance characteristics, testing methodology, manufacturing practices, 
product standards, scientific protocols, compliance criteria, ingredient specifications, 
labeling, and terminology. 
 
G.  What Are Reference Materials or Physical Standards? 
 
For purpose of this guidance, reference materials or physical standards are typically 
highly characterized reagents or substances that are distributed to assure consistency, 
quality, and safety of regulated products.  Reference materials are materials that are 
considered to be sufficiently homogeneous and stable, with respect to one or more 
specified attributes, and that have been established to be suitable for their intended use in 
a measurement process (for example, measurement of potency or product consistency). 
 
H.  What Are Data Standards? 
 
For purpose of this guidance, data standards are defined rules, formats, and terminologies 
that provide structure and consistency for exchange and utilization of data.  Data 
standards may describe the data elements and relationships necessary to achieve the 
unambiguous exchange of information between disparate information systems. 
 
I.  What Are Performance Standards? 
 
For purpose of this guidance and as set forth in Circular A-119, performance standards 
state requirements in terms of required results without stating the methods for achieving 
those results.  A performance standard may define the functional requirements for the 
item, operational requirements, and/or interface and interchangeability characteristics.  
(In contrast, a prescriptive standard may specify design requirements, such as materials to 
be used, how a requirement is to be achieved, or how an item is to be fabricated or 
constructed).  (Ref. 1). 
 
 
IV.  HOW ARE VOLUNTARY STANDARDS DEVELOPED? 
 
SDOs develop or sponsor the development of voluntary standards that can be used by a person 
involved either in the manufacture, distribution, sale, or use of products or services or in the legal 
regulation of such products and services.  SDO standard-setting activities include the 
development of performance characteristics, testing methodology, manufacturing practices, 
4  Contains Nonbinding Recommendations 
 
product standards, scientific protocols, compliance criteria, ingredient specifications, labeling, 
and terminology. 
 
Participants in the standards development process are individuals who represent stakeholders and 
possess expertise in the particular area for which a standard is under development.  Although 
standards development procedures vary among SDOs, the process typically begins with 
identifying the need for a written/documentary standard or a reference material/physical standard 
and gathering experts to develop the standard.  Drafts of written standards are circulated for 
comment, voting, editing, and publishing.  Reference materials/physical standards may be 
distributed for testing and certification to ensure that they serve their intended purpose. 
 
CBER staff often participate in the development of voluntary standards.  CBER participation in 
the development of a particular standard does not constitute endorsement of that standard. 
Guidelines for FDA participation in standards development activities are outlined in the FDA 
Staff Manual Guide for the Development and Use of Standards, SMG 9100.1 (Ref. 3). 
 
 
V.  WHAT ARE THE BENEFITS OF USING VOLUNTARY STANDARDS? 
 
In line with OMB Circular A-119 (Ref. 1) and the NTTAA (Ref. 2), the use of existing standards 
minimizes the need for government-unique standards.  By leveraging stakeholders efforts to 
develop standards, FDA can eliminate the cost to the Federal Government associated with the 
development of government-unique standards and promote international harmonization of 
standards that are acceptable to FDA. 
 
CBER participates in SDOs to become familiar with standards as they are developed, updated, or 
withdrawn.  CBER participation facilitates the development of standards that are not in conflict 
with or duplicative of FDA regulations or policies.  CBERs participation also increases the 
likelihood that the standards under development will ultimately be suitable for use in regulatory 
submissions reviewed by CBER.   
 
CBER encourages the use of appropriate standards in the development of CBER-regulated 
medical products.  Sponsors wider use of existing relevant voluntary consensus standards can 
facilitate development by reducing the need to develop unique methods and/or reference 
materials for individual products.  The use of standards can facilitate product development and 
reduce the amount of documentation needed in a regulatory submission, thus contributing to a 
more efficient submission evaluation and, ultimately, improving time to market. 
 
 
VI.  WHAT IS CBERS POLICY ON ACCEPTING STANDARDS USED IN 
REGULATORY SUBMISSIONS? 
 
A.  What Is CBERs Policy on Use of Standards in Regulatory Submissions?  
 
CBER encourages sponsors of regulatory submissions and manufacturers to use 
appropriate voluntary consensus standards.  Further, CBER intends to preferentially use 
5  Contains Nonbinding Recommendations 
 
internationally harmonized standards (standards developed by organizations typically 
involving representatives from many countries) when those standards represent the most 
appropriate standards for a specific purpose and are not in conflict with U.S. law (Refs. 3, 
4).  
 
Sponsors should confirm that the standard was used as published or state how they 
deviated from the assay described in the standard.  Standards are typically reviewed by 
the SDOs every 5 years to ensure that the standard continues to be relevant and to assess 
whether the standard needs to be updated because of advances in technology.  If the 
standard is revised and the sponsor chooses to use the updated version of the standard, 
then the sponsor should provide an amendment to the regulatory file, stating the version 
of the standard that is currently in use.  
 
For example, a sponsor utilizing a differentiation assay to measure the potential of 
progenitor stem cells per a relevant standard (e.g., Standard ABC, Version X, Date Y) 
would note that it either used the standard as written or describe how it deviated from the 
assay described in the standard. 
 
Guidance documents published by FDA may reference standards, including test methods, 
practices, guides, and material specifications, developed through voluntary consensus 
processes with the regulated industry and other interested parties.  For example, the 
CBER/Center for Devices and Radiological Health (CDRH) joint guidance, Guidance 
for Industry: Preparation of IDEs and INDs for Products Intended to Repair or Replace 
Knee Cartilage (Ref. 5) references ASTM F2451-05, Standard Guide for in vivo 
Assessment of Implantable Devices Intended to Repair or Regenerate Articular 
Cartilage, reapproved by ASTM in 2010.  In that guidance, the Agency recommends 
consulting the ASTM standard for the development of animal models and the testing of 
implantable devices (cartilage repair products). 
 
Sponsors are advised to discuss the proposed use of a particular standard or portion of a 
standard with CBER prior to implementation in order to determine if the standard is 
appropriate for the intended regulatory purpose.  Sponsors should contact the relevant 
CBER Office responsible for regulatory oversight (e.g., the Office of Biostatistics and 
Epidemiology, Office of Blood Research and Review, Office of Tissues and Advanced 
Therapies, Office of Compliance and Biologics Quality, or Office of Vaccines Research 
and Review.  OCOD may be contacted at industry.biologics@fda.hhs.gov for advice on 
which office is responsible for the review of a particular product.  When referencing a 
standard in a regulatory submission, sponsors should provide the name of the SDO, the 
title of the standard, and the version of the standard.  The use of voluntary standards is 
not mandatory. 
 
CBER recommends the following to those considering the use of a standard in support of 
their regulatory application. 
 
1.  When using a standard, the sponsor should provide a complete reference 
for the standard in the regulatory submission. 
6  Contains Nonbinding Recommendations 
 
 
2.  Once CBER has determined that a version of a standard is acceptable, the 
sponsor should implement a new version of that standard after the sponsor 
qualifies and validates the changes and the Agency determines it is 
acceptable.  The sponsor should submit the information requesting 
implementation of a new version as an amendment or supplement to the 
regulatory file. 
 
3.  Written/Documentary Standards:  A sponsor may use appropriate 
written/documentary standards that describe a process or assay used to 
assess a manufacturing intermediate or final product. 
 
4.  Reference Materials/Physical Standards:  A sponsor may also utilize an 
appropriate physical standard or reference material in the development and 
testing of their product.  Examples of reference materials include 
commercially supplied reference standards obtained from a reputable 
commercial source; other materials of documented purity certified by an 
analytical laboratory or other noncommercial establishment; and a well-
characterized lot of the product, itself. 
 
CBER prepares, calibrates, holds, and distributes certain official U.S. 
reference standards and reagents to assist firms holding approved BLAs, 
NDAs, or INDs.  
 
The sponsor should provide information on the reference standards or 
reference materials used for testing the drug substance or drug product in 
the regulatory submission.  CBER recommends providing the source and 
lot number, expiration date, certificates of analyses when available, and/or 
internally or externally generated evidence of identity and purity for each 
reference standard.  In cases where the sponsor would be using a well-
characterized lot of their product, CBER recommends that the sponsor 
reserve and maintain a sufficient supply of the product to serve as a 
reference material.  
 
An in-house standard should be maintained in accordance with the 
regulated reference standard to which it is traceable unless a sponsor 
demonstrates that maintaining the in-house standard is otherwise 
appropriate.  However, please note that changes to the way an in-house 
standard is maintained must be reported to the Agency, in accordance with 
FDA regulations in Title 21 of the Code of Federal Regulations (CFR) 
312.31 for INDs; 21 CFR 314.70 for NDAs; or 21 CFR 601.12 for BLAs. 
 
If the sponsor has questions about whether the use of a particular standard 
is appropriate, the sponsor should discuss its use with the appropriate 
product office or CBERs OCBQ Division of Biological Standards and 
7  Contains Nonbinding Recommendations 
 
Quality Control, as appropriate, before using that standard in a regulatory 
submission. 
 
5.  Compendial Standards:  Compendial standards may be used to support a 
regulatory submission once CBER reviews and determines it is 
appropriate. 
 
6.  Data Standards:  Data standards can help promote effective and efficient 
review of regulatory submissions.  Examples of data standards include 
Structured Product Labeling, Health Level 7 Stability Standard, etc.  
Submission data standards are listed in the FDA Data Standards Catalog 
established in the Standardized Study Data Guidance (Ref. 6).  For more 
information, see the FDA Data Standards Catalog, available at the FDA 
Resources for Data Standards website: 
https://www.fda.gov/ForIndustry/DataStandards/default.htm. 
 
B.  What if a Product Is Regulated by CBER as a Device? 
 
The use of consensus standards is not mandatory for medical device regulatory 
submissions unless the consensus standard has been incorporated by reference into a 
regulation.  For devices regulated by CBER, a sponsor or manufacturer of a medical 
device may use either standards that have been recognized by CDRH or non-
recognized standards to support regulatory submissions for medical devices.  In 
accordance with the Food and Drug Administration Modernization Act of 1997, CDRH 
maintains a list of Recognized Consensus Standards that can be found at 
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm.  Standards 
referenced in the CFR can be found in the Standards Incorporated by Reference (SIBR) 
Database at https://www.nist.gov/standardsgov/what-we-do/federal-policy-standards/sibr.  
For additional information on the standards recognition program, refer to the 
CDRH/CBER joint guidance, entitled Appropriate Use of Voluntary Consensus 
Standards in Premarket Submissions for Medical Devices; Guidance for Industry and 
Food and Drug Administration Staff (Ref. 7). 
 
C.  Does CBER Take Accreditation Standards into Consideration when 
Assessing Compliance with CBER Regulatory Requirements? 
 
Accreditation standards are set forth by accreditation organizations to ensure that certain 
criteria are met for a specified process or system.  Note that these organizations generally 
do not meet the definition of a voluntary consensus standards body.  CBER may, when it 
deems appropriate, take accreditation standards established by these organizations into 
consideration when assessing compliance with CBER regulatory requirements.  
Examples of accreditation organizations include AABB (transfusion medicine and 
cellular therapies), Foundation for the Accreditation of Cellular Therapy (cellular 
therapy), International Council for Commonality in Blood Banking Automation 
(identification and labeling of blood and tissues), and American Association of Tissue 
Banks (tissue banking).  CBER has, for example, recognized certain blood donor history  
8  Contains Nonbinding Recommendations 
 
 
 
 
questionnaires developed by AABB as acceptable for use by blood collection  
establishments to collect donor history information from donors of blood and blood 
components.1 
 
D.  Can Standards Developed by the World Health Organization (WHO) Be 
Used to Support a CBER Regulatory Submission? 
 
Although the WHO does not meet the definition of an SDO, the WHO and the standards 
it develops have a role in the development, manufacturing, and use of certain medical 
products. 
 
WHO develops both written standards and physical standards/reference materials that, 
when appropriate, can be used to support a regulatory submission.  Written standards are 
published on the WHO website as recommendations and guidelines.  WHO also provides 
biological reference materials for the manufacture and control of certain manufactured 
products. 
 
                                                 
1 Implementation of Acceptable Full-Length and Abbreviated Donor History Questionnaires and Accompanying 
Materials for Use in Screening Donors of Blood and Blood Components; Guidance for Industry, dated May 2016, 
can be found via the following link: 
https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/B
lood/UCM273685.pdf.  
9  Contains Nonbinding Recommendations 
 
VII.  REFERENCES  
 
1.  OMB Circular A-119: Federal Participation in the Development and Use of Voluntary 
Consensus Standards and in Conformity Assessment Activities, January 2016, 
https://obamawhitehouse.archives.gov/sites/default/files/omb/inforeg/revised_circular_a-
119_as_of_1_22.pdf 
2.  National Technology Transfer and Advancement Act of 1995.  Pub. L. 104-113, March 
1996, Including Amendment by Pub. L. 107-107, section 1115, December 2001, 
https://www.nist.gov/standardsgov/national-technology-transfer-and-advancement-act-
1995 
3.  FDA Staff Manual Guides, Volume IV  Agency Program Directives, Common 
Standards, Development and Use of Standards, SMG 9100.1, June 2012, 
https://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/StaffManualGuides/
UCM240278.pdf 
4.  Federal Register Notice:  International Harmonization; Policy on Standards (60 FR 
53078, October 11,1995), https://www.gpo.gov/fdsys/pkg/FR-1995-10-11/pdf/95-
25070.pdf 
5.  Guidance for Industry:  Preparation of IDEs and INDs for Products Intended to Repair or 
Replace Knee Cartilage, December 2011,  
https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulator
yInformation/Guidances/CellularandGeneTherapy/UCM288011.pdf 
6.  Providing Regulatory Submissions In Electronic Format  Standardized Study Data; 
Guidance for Industry, December 2014, 
https://www.fda.gov/downloads/drugs/guidances/ucm292334.pdf 
7.  Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for 
Medical Devices; Guidance for Industry and Food and Drug Administration Staff, 
September 2018,  
https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/Guidan
ceDocuments/ucm077295.pdf 
 
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