Guidance to Industry

Preparing Supporting Summaries for 

Single Tier (Single Label Claim) Effectiveness Statements

Contents

I. Overview .................................................................................................................................... 2

II. Scope of Products Affected by Single-Tier............................................................................... 2

III. Scope of Studies Requiring Single-Tier Summaries ............................................................... 2

IV. Individual Study Summary (ISS) Procedure ........................................................................... 3

V. ISS template .............................................................................................................................. 4

A. First page ............................................................................................................................... 4

B. Subsequent page(s) ................................................................................................................ 5

VI. Data Requirements................................................................................................................... 7

A. Efficacy Studies .................................................................................................................... 7

B. Safety Studies ........................................................................................................................ 7

C. Exceptions for Historical Studies .......................................................................................... 8

VII. Product Compilation Summaries (PCSs) ............................................................................... 9
Guidance to Industry: Preparing Supporting Summaries for Single-Tier Effectiveness Statements

September 1, 2020 Page 2 of 10

I. Overview

As part of a movement in 2015 toward single-tier effectiveness statements, 9CFR 112.5(b) was 

amended to require publication of efficacy and safety study summaries on the APHIS website 

productdata.aphis.usda.gov. This document provides details to licensees, permittees, and 

applicants on preparing and submitting information for those summaries.

A summary of a single study is known herein as an Individual Study Summary (ISS). It is 

prepared by the licensee/permittee and reviewed/edited/cleared by the Center for Veterinary 

Biologics (CVB) for standard content and appearance. All of the ISSs applicable to a single 

biological product are then compiled into a Product Compilation Summary (PCS), which is 

posted to productdata.aphis.usda.gov. The compilation is performed by the CVB.

II. Scope of Products Affected by Single-Tier

Vaccines (including prescription platform products), bacterins, toxoids, and immunomodulators 

are included under the scope of the new rule. 

Products exempted include: antibody products, diagnostic test kits, autogenous, and allergenic 

extracts.

III. Scope of Studies Requiring Single-Tier Summaries

1. Prepare Individual Study Summaries for the following:

• Efficacy studies directly supporting licensure of a product

o Host animal vaccination-challenge or field efficacy studies (short-term and

duration of immunity): pivotal pre-license efficacy and any subsequent studies

that change claims or instructions for use.

o Host animal vaccination-challenge to establish immunogenicity for the addition of

new influenza subtypes in licensed products per VSM 800.111.

o Codified tests highly correlated to host animal efficacy, which the CVB allows as

fulfillment of pivotal efficacy requirements for certain agents (e.g., Clostridium

tetani, and select other Clostridium spp serology)

• Safety studies

o Routine field studies (VSM 800.204)

o Additional safety studies to support specific claims (e.g., safe for use in pregnant

animals).

2. Individual Study Summaries are typically not required for the following, unless specifically

requested by the CVB:

• Reasonable expectation of efficacy for a conditional license

• Reference qualification studies that merely confirm the findings of prior pivotal efficacy

• Backpassage or shed/spread studies
Guidance to Industry: Preparing Supporting Summaries for Single-Tier Effectiveness Statements

September 1, 2020 Page 3 of 10

• Proof-of-concept efficacy studies or studies conducted solely to fulfill requirements for

foreign registration

• Component compatibility studies other than host animal vaccination-challenge (e.g.,

serological non-inferiority)

• Overdose safety studies

• Residue clearance studies

• Studies for products solely for official/emergency use by APHIS

3. Full Individual Study Summaries are required for applicable studies submitted to the CVB on,

or after January 1, 2007. Studies submitted prior to 2007 do not require a full summary,

although one may be submitted voluntarily. Alternatively, a placeholder, as described in Section

VI.C below, may be submitted. All product classes within the scope of single tier must have

single-tier language on labeling, even if only placeholders are published on the CVB website.

IV. Individual Study Summary (ISS) Procedure

1. Use the ISS template provided by the CVB. Refer to the line-wise instructions provided

in the following section for details on how to prepare the ISS. Submit the ISS to CVB as

a Microsoft Word document to facilitate editing by CVB. Contact the CVB at

CVB.Single.Tier@usda.gov if you do not have access to Microsoft Word software.

2. Submit ISSs for previously accepted studies as they are available. See the single tier

implementation timeline for current goals for completion.

• Co-submit an electronic copy of the historical study report if it was originally

submitted as a paper copy. This will help the CVB expand its collection of digitized

key documents.

• If known, also provide the submission date and CVB mail log number of the original

study.

• Include a copy of the CVB acceptance letter if it is readily available, but latitude is

given for letters that would be problematic to locate.

3. Submit ISSs for new studies after the study report has been accepted.

4. Please submit ISSs electronically, preferably using the NCAH Portal. For non-portal

users, provide the submission electronically on a CD, DVD, memory stick, or other

similar device. As a reminder, the device will remain with the CVB and will not be

returned to the firm.

Complete APHIS Form 2049 and include the Microsoft Word document of the ISS and

additional related reports/letters as applicable. Use the following values on APHIS Form

2049 to clearly identify the submissions:

• Submission type=Historical Study Summary

• Product Codes: Enter all current product codes to which the study applies. Due to

acquisitions, mergers, and the subsequent licensure of related products, the codes may
Guidance to Industry: Preparing Supporting Summaries for Single-Tier Effectiveness Statements

September 1, 2020 Page 4 of 10

differ from those originally associated with the study. Justify the addition/substitution 

of codes that were not associated with the original study report. 

• Brief Description: Indicate whether the submission is a full ISS or only a

placeholder and other relevant information for the study

• Attachment type (NCAH Portal users only): Use Draft Individual Summary to

upload the ISS. Use Incoming Document (Core) for any other co-submitted

documents. Add the study identifier to the report or the Draft Individual Summary.

5. ISSs will be reviewed for acceptable format, clarity, and consistency by the Single-Tier

Implementation Team. The Team is a small group of reviewers who have developed

expertise in ISSs. If any major revisions are needed, the CVB will maintain transparency 

with the submitter to generate an acceptable ISS.

6. Once the ISS is cleared for publication, the cleared version will be converted by the CVB

to PDF, and a copy will be provided to the submitter for the firm’s files. Firms will be

given two weeks to contact the CVB at CVB.Single.Tier@usda.gov if issues with the 

cleared ISS are noted. This ISS may then appear in a Product Compilation Summary

(PCS) for any applicable product.

V. ISS template

A. First page

The first page of the ISS template contains a table with identifying information that will not be 

included when this ISS is incorporated into a PCS by the CVB. PCSs will have their own cover 

page containing appropriate identifying information for the Product. To facilitate computerized 

assembly of the PCS by the CVB, the table on page 1 of an ISS template must be the only item 

on Page 1 of the completed document. 

First page table:

Original Establishment 

Number

Enter the Est # from which the study was submitted, even if (as 

in the case of split manufacture or acquisition/merger) the study 

may pertain to another Establishment’s final-use product

Original Product Code Enter the original code(s) of the product under which the study 

was submitted. 

Current Product Codes Enter the current Est # if it is different from the original Est #. 

Enter any current codes to which the study applies. We realize 

this may not agree with the original code if the product has been 

subject to acquisitions and mergers. 

Study Identifier The CVB strongly encourages applicants to create a unique ID 

for studies. Enter the identifier, if one was created. The CVB 

recognizes there may not be a unique ID for certain historical

studies. 
Guidance to Industry: Preparing Supporting Summaries for Single-Tier Effectiveness Statements

September 1, 2020 Page 5 of 10

Date Study Submitted Enter the date the efficacy/safety study was submitted to the 

CVB (not the submission date for the Individual Study Summary 

if it is submitted after the study was reviewed)

CVB Mail Log ID

containing study

For historical studies, the CVB Mail Log (ML) ID of the full 

study submission will differ from the ML assigned to the 

individual study summary because they are being submitted 

separately. In many cases, the ML ID assigned to the full study 

report may not be known to the firm. The CVB may add this 

information later if we can trace the ML # in our records. Some 

studies may pre-date any kind of CVB Mail Log. 

B. Subsequent page(s)

The following table, to begin on page 2 of a completed ISS, will appear in PCSs.

Study Type Enter Efficacy or Safety.

Pertaining to • Enter the agent against which efficacy is being

demonstrated. For influenza products, include the

influenza strain by WHO nomenclature (e.g.,

A/California/04/2009(H1N1).

• For BVD products, enter the type (e.g. Type 1, Type 2).

• For PCV products, enter the genotype (e.g. 2).

Enter ALL for safety studies. 

Study Purpose Be succinct and non-technical, using plain language. 

Examples: 

• To demonstrate efficacy against diarrhea in piglets

nursing vaccinated sows

• To demonstrate efficacy against respiratory disease one

year after vaccination

• To demonstrate safety under field conditions

• To demonstrate safety in pregnant animals

Product Administration Include the number of doses, interval between doses, and the 

route of administration. 

If the product administered is a platform product, include the 

identity of the inserted gene for the serial used in the study. 

Study Animals Include the animal species, age at first product administration, 

and number of animals per treatment group. 

For efficacy studies, the number of animals per treatment group 

should be the number included in the final study analysis. 

For field safety trials, all animals enrolled in the study should be 

represented. State an age range indicating the number of animals 

at the minimum age.
Guidance to Industry: Preparing Supporting Summaries for Single-Tier Effectiveness Statements

September 1, 2020 Page 6 of 10

Challenge Description Include the challenge agent and time interval between the last 

product dose and challenge. If the challenge agent is a generally 

recognized strain (e.g., Singer strain of BVD1 or Rickard strain 

of FeLV), please indicate it.) 

• Bovine Virus Diarrhea Virus-state the type, subtype, and

strain.

• Infectious Bronchitis Virus-state the type.

• Infectious Bursal Disease Virus-state the type.

• Influenza Virus-state the subtype and strain. Designate

the strain according to accepted standards of influenza

virus nomenclature.

• Newcastle Disease Virus-state the strain.

• Porcine Circovirus-state the type and subtype.

• Rabies Virus-state the strain.

Enter “Not applicable” for safety studies.

Interval observed after 

challenge

Specify how long, and how frequently, animals were monitored 

for safety studies and after challenge for efficacy studies.

Results

***See the following section of this document for data 

formatting requirements.*** 

Efficacy: Focus on results that provided the primary basis for 

regulatory acceptance. Avoid myriad unremarkable secondary 

findings. 

Define any complex case definitions and indicate when the test 

was conducted according to a codified Standard Requirement. 

Explain scientific/medical terms in plain language. 

If multiple dose concentrations or different routes of 

administrations were tested, present only the data for the 

formulation/route that was approved for licensure. 

Safety: Account for all enrolled animals by adverse event 

observed. 

Presentation:

If a table or graphical presentation does not fit easily in the 

Results block of the ISS template, append additional pages to the 

template and refer the user to the added pages. If the data fit 

better on 8.5 x 11” pages in landscape view, it is permissible to 

rotate the data sideways on portrait-oriented pages. (Example 

ISS #9 contains rotated text.) Do not rotate individual pages 

within the Word document, however, as this creates problems 

during the CVB’s automated compilation of a Product 

Compilation Summary.
Guidance to Industry: Preparing Supporting Summaries for Single-Tier Effectiveness Statements

September 1, 2020 Page 7 of 10

If data were presented in tabular format in the study report, the 

same table may be copied/pasted into the ISS, provided there is 

adequate resolution to retain readability.

VI. Data Requirements

Example ISSs for a variety of study designs are available on the CVB website. These are not 

meant to reflect the only way that study data can be presented, but they do provide acceptable 

examples. All presentations of study data must meet the following guidelines:

A. Efficacy Studies

1. Raw data: All efficacy ISSs must present raw study data. The ISSs are intended to meet

the needs of a wide variety of readers.

Strive to present raw data in a meaningful, concise manner, but do not combine/collapse data 

so that information is lost. 

• Example: In example ISS #1, it would have been inappropriate to reduce the data for

each calf to an overall yes/no outcome, as there were two parameters (virus and

antibody) being evaluated. Information about individual calves would have been lost

if those findings were combined into a single composite outcome.

2. Summarizations: Limited high-level summaries are permissible, but not required, to

accommodate readers who do not wish to examine raw data. The following types of

summarizations are allowed in addition to raw data:

• 5-number summaries are allowed for continuous numerical data, such as lung lesion

scores or the duration of an event. Example ISS #5 shows this type of

summarization.

• Totals are allowed for dichotomous or qualitative data, such as total mortalities or the

number of animals meeting the criteria of a multi-factorial case definition. Express

totals as the number affected over the total number (e.g., 9 of 25 died). Similarly,

percentages are also allowed as long as the numbers are included (e.g. 9 of 25 (36%)).

• It is permissible to include a “final classification” column at end of raw data to show

the disposition for each animal (positive or negative). Example ISS #7 illustrates this

type of summarization.

Do not include other summarizations, such as averages or means. Do not include 

statistical analyses, such as prevented fractions or p-values.
September 1, 2020 Page 8 of 10

Guidance to Industry: Preparing Supporting Summaries for Single-Tier Effectiveness Statements 

1. Account for every animal enrolled in the study. For the FST ISS, an animal is

considered enrolled once it has received the first vaccination. Indicate the number of

animals that completed the study (with or without an adverse event (AE)) and the

number that did not complete the study (with or without an AE). In some

circumstances it may be acceptable to provide this information in narrative form

rather than in a table.

2. Present a table listing the AE by category.

• The number of AEs may not match the number of animals experiencing AEs,

since an animal may experience more than one AE.

• AEs that are clearly considered to have a plausible cause other than

vaccination may be included in a separate category. (Example: An animal

dies a few days after vaccination due to accidental trauma). The explanation

must be in the study report with adequate justification (i.e., definitive data) to

rule out vaccination. Such AEs may be indicated as “affirmed by licensee to

have a cause other than vaccination.” Example ISS #15 shows this type of

summary.

• Explanatory notes may be included to indicate circumstances that may affect

the interpretation of the observations or where there is not a sufficient degree

of certainty to designate the AEs as having a cause other than vaccination. In

that case a short, concise explanation may be provided below the table.

(Example: Pigs vaccinated with a Mycoplasma hyopneumoniae bacterin are

part of a herd that experiences an influenza outbreak a couple of days later.)

Example ISS #16 shows this type of summary.

3. Where appropriate, present a table of injection site swelling. Tabulate local injection

site swelling by size and duration. Example ISS #10 shows this type of summary.

4. For poultry studies, include data for mortality, hatchability, and condemnation as

required or on a case-by-case basis. Hatchability data are required for products

administered in ovo. If the data are not available, make an explanatory notation.

Mortality, hatchability, and condemnation data may be presented as percentages as

long as total animal numbers are reported. Example ISS #14 shows this type of

summary.

C. Exceptions for Historical Studies

The data requirements described in Sections V.A and V.B are expected for all summaries for

studies conducted in 2017 forward. It is highly likely that studies of the past several years

also will have the detail necessary to meet these requirements. The CVB recognizes that

some older study reports may not have the detail necessary to meet all of the summary

For field safety trials (FST) according to VSM 800.204, a tabular presentation is recommended. 

The presentation may be in one or more tables to present the data adequately. 

B. Safety Studies
Guidance to Industry: Preparing Supporting Summaries for Single-Tier Effectiveness Statements

September 1, 2020 Page 9 of 10

requirements, and these will be handled on a case-by-case basis to best present the available 

data.

If a full ISS will not be submitted for a study conducted prior to 2007, submit a placeholder 

ISS instead. Follow the format shown in ISS Example #17. 

VII. Product Compilation Summaries (PCSs)

All of the ISSs for a given product are appended together to create a PCS. The compilation is a 

computerized process performed by CVB data systems. An example PCS is on the CVB 

website.

A courtesy copy of each PCS is then sent to the firm. Firms are asked to provide any feedback 

on errors to cvb.single.tier@usda.gov within 2 weeks. Since the PCSs are merely a grouping 

of previously cleared ISSs, errors/concerns should be rare. 

• PCSs for new products will be generated and sent to the firm at the time of product

licensure. There will be a delay of at least 28 days before posting the PCS to the

productdata.aphis.usda.gov website. Firms wishing to have a PCS posted earlier than 28

days after licensure can request an earlier date by emailing

cvb.single.tier@usda.gov. (Do not email your firm’s reviewer.)

• PCSs for currently licensed products may be sent to the firm at any time after all of the

component ISSs have been cleared and at least 28 days prior to posting the PCS on

productdata.aphis.usda.gov.

• If a product is licensed and the PCS has not yet been published on

productdata.aphis.usda.gov, firms may distribute their copy of the PCS, without alteration

or embellishment, to interested parties.

• Updated PCSs may be generated if an eligible study is conducted after initial product

licensure.

• French versions of published PCSs may be considered for publication if approved and

submitted by the Canadian Food Inspection Agency (CFIA) to the CVB. Licensees and

permittees should consult with CFIA when PCS revisions are needed to ensure

consistency with the CVB generated PCS.

VIII. Updating Product Codes Associated With Approved ISSs

Licensees and permittees may need to update the list of product codes associated with a 

cleared (approved) ISS. When this occurs, use the following process: 

• Do NOT resubmit the ISS.

• Make a formal submission with the following parameters:

o Submission type=Historical Study Summary

o Brief Description=”Request to update product codes associated with previously

cleared ISS”
Guidance to Industry: Preparing Supporting Summaries for Single-Tier Effectiveness Statements

September 1, 2020 Page 10 of 10

o Related Submissions = ML of submission where ISS was processed

• Attach a justification for each code addition

The CVB will evaluate the request. If eligible, a new ISS with only the newly requested product 

code(s) will be generated by the CVB based on the previously cleared (approved) ISS, and then

returned under the new submission. The previously cleared (approved) ISS will not be changed. 

If the codes are not eligible to be added to a previously cleared (approved) ISS, the request will 

be denied.