Guidance for Industry 
User Fee Waivers for FDC 
and Co-Packaged HIV Drugs 
for PEPFAR 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
February 2007 
 
User Fees 
   
Guidance for Industry 
User Fee Waivers for FDC 
and Co-Packaged HIV Drugs 
for PEPFAR 
 
 
 
Additional copies are available from: 
Office of Training and Communication 
Division of Drug Information, HFD-240 
Center for Drug Evaluation and Research 
Food and Drug Administration 
5600 Fishers Lane 
Rockville, MD  20857 
(Tel) 301-827-4573 
 http://www.fda.gov/cder/guidance/index.htm 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
February 2007 
 
User Fees 
 
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TABLE OF CONTENTS 
 
 
 
 
I.  INTRODUCTION.............................................................................................................1 
II.  BACKGROUND...............................................................................................................1 
III.  SOME APPLICATIONS WILL NOT BE ASSESSED FEES; SOME WILL BE 
ASSESSED HALF THE FEE..........................................................................................2 
IV.  WAIVERS OF FEES........................................................................................................3 
A.   Application Fees.............................................................................................................................3 
B.  Annual Product and Establishment Fees.....................................................................................5 
ATTACHMENT:  SUMMARY OF AVAILABLE EXEMPTIONS AND WAIVERS..........7 
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  Contains Nonbinding Recommendations 
1
Guidance for Industry  
User Fee Waivers for FDC and Co-Packaged HIV Drugs for 
PEPFAR 
 
 
 
This represents 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 satisfies 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, call the appropriate 
number listed on the title page of this guidance.  
 
 
 
 
I.  INTRODUCTION 
 
This guidance describes the circumstances under which user fees will not be assessed under the 
Prescription Drug User Fee Act (PDUFA) for some applications for fixed dose combination 
(FDC) and co-packaged versions of previously approved antiretroviral therapies for the treatment 
of human immunodeficiency virus (HIV).  The guidance also describes circumstances under 
which many of the applications, products, and establishments that will be assessed fees may be 
eligible for a public health or a barrier-to-innovation waiver.  We expect that most of the 
applications, products, and establishments for FDC and co-packaged HIV therapies proposed 
for use in the President's Emergency Plan for AIDs Relief (PEPFAR) will either not be 
assessed fees in the first instance or will qualify for a waiver under the "other  circumstances" 
part of the barrier-to-innovation user fee waiver.  See the Attachment at the end of the guidance 
for a summary of available exemptions and waivers. 
 
FDA's guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the Agency's 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 Agency guidances means that something is suggested or 
recommended, but not required.  
 
 
II.  BACKGROUND 
 
                                                 
1 This guidance has been prepared by the Division of Antiviral Drug Products in the Center for Drug Evaluation and 
Research (CDER), in cooperation with the Office of Regulatory Policy, CDER. 
 
All guidances mentioned in this document are available at http://www.fda.gov/cder/guidance/index.htm. 
 
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2/6/2007  Contains Nonbinding Recommendations 
As part of the President's Emergency Plan for AIDs Relief, the President committed sizeable 
resources, including $15 billion over a 5-year period to fund a program to develop programs to 
address the treatment of HIV. 2 
 
In May 2004, to encourage applicants to submit applications for HIV combination therapies that 
can be used in PEPFAR, FDA issued a draft guidance entitled Fixed Dose Combination and Co-
Packaged Drug Products for the Treatment of HIV (fixed-dose guidance).3  Attachments to the 
fixed dose guidance described some scenarios for approval of fixed dose combination (FDC) or 
co-packaged products for the treatment of HIV, and provided examples of drug combinations 
considered acceptable for FDC/co-packaging and examples of those not considered acceptable 
for FDC/co-packaging.  The guidance also explained that the Federal Food, Drug, and Cosmetic 
Act (the Act) provides for certain circumstances in which FDA can grant applicants a waiver or 
reduction in user fees normally assessed for drug applications, drug products, and establishments 
where drugs are made.  The fixed dose guidance stated that FDA was evaluating the 
circumstances under which it can grant user fee waivers or reductions for applicants developing 
FDC and co-packaged versions of previously approved antiretroviral therapies for the treatment 
of HIV.  
 
Several potential applicants have asked that we clarify whether applicants submitting drug 
applications covered by the fixed dose guidance for use in PEPFAR will be required to pay user 
fees under PDUFA and, if so, whether they would be eligible for a waiver of those fees.   
 
 
III.  SOME APPLICATIONS WILL NOT BE ASSESSED FEES; SOME WILL BE 
ASSESSED HALF THE FEE 
 
Under PDUFA, the following types of drug applications are not assessed user fees: 
 
  Abbreviated new drug applications (ANDAs) submitted under section 505(j) of the Act 
(section 735(1)) 
 
  Applications submitted under 505(b)(2) of the Act that do not request approval of  (1) a 
new molecular entity (i.e., an active moiety that has not been approved under an 
application under 505(b)) or (2) an indication for a use that has not been approved under 
an application under 505(b) ( 735(1)(B)) 
 
Most applications submitted under Scenarios 2 and 3 of Attachment A to the draft fixed dose 
guidance could qualify for these fee exemptions.   
 
                                                 
2 White House Fact Sheet The Presidents Emergency Plan for AIDS Relief, available on the Internet at 
www.whitehouse.gov/news/releases/2003/01/20030129-1.html. 
 
3 The draft guidance has been finalized and renamed Fixed Dose Combination, Co-Packaged Drug Products, and 
Single-Entity Versions of Previously Approved Antiretrovirals for the Treatment of HIV (HIV guidance).  The final 
HIV guidance is available on the Internet at www.fda.gov/cder/guidance. 
  2 Contains Nonbinding Recommendations 
Any ANDA submitted under section 505(j) of the Act would be exempt.  However, because only 
certain 505(b)(2) applications are exempt, it is important that potential applicants who do not 
want to be assessed fees be advised to use active ingredients submitted in applications that have 
already been approved under section 505(b) (that is, they can use any of the ingredients listed in 
Attachment B to the fixed dose guidance), and they should not seek any new indications for a 
use.  It is particularly important that they strictly follow the approved labeling for the individual 
ingredients.  If, for example, applicants seek a different use of the drug, a different dosing 
regimen or route of administration, use in a new population, or if they compare their product to 
others in the labeling, they will not qualify for the 505(b)(2) exemption from fees. 
 
Finally, any application submitted under 505(b)(1) or 505(b)(2) of the Act that does not require 
clinical data for approval would only be assessed a half fee under the Act (section 736(a)(1)(A)).  
This half fee would be $448,100 for fiscal year 2007.4  Bioavailability and bioequivalence data 
are not considered clinical data for purposes of assessing user fees.5   
 
 
IV.  WAIVERS OF FEES 
 
  A.   Application Fees 
 
Sponsors of applications that will be assessed either a full or a half fee may qualify for waivers 
of their application fee under several provisions of PDUFA.  Waivers must be requested of FDA 
not later than 180 days after the fees are due,6 and FDA encourages firms to request a waiver at 
least 45 days in advance of submission of an application so that the request can be evaluated 
before the fee is due.7 
 
The waivers most likely to be available to PEPFAR participants are: 
  The small business waiver, which provides for a complete waiver of the application fee for 
any company with less than 500 employees (including affiliated companies) for the first 
human drug application the company (including its affiliates) submits.8  Applicants must 
request this waiver from FDA and provide evidence to the Small Business Administration 
regarding the size of the company.  
                                                 
4 October 1, 2006, through September 30, 2007. 
 
5 See FDA's guidance for industry on Submitting Separate Marketing Applications and Clinical Data for Purposes 
of Assessing User Fees. 
 
6 Section 736(i), 21 U.S.C. 379h(i). 
 
7 Normally, FDA encourages the submission of requests for waivers 90 days in advance of the submission of an 
application.  However, to further reduce the burden on sponsors interested in making products available under 
PEPFAR, FDA will expedite the processing of waiver requests and try to process such requests within 45 days. 
 
8 Section 736(d)(3), 21 U.S.C. 379h(d)(3). 
 
  3 Contains Nonbinding Recommendations 
  The public health waiver and the barrier-to-innovation waiver, which provide for waivers of 
application fees and annual product and establishment fees for companies that meet the 
criteria.9   
FDAs Attachment G  Draft Interim Guidance Document for Waivers of and Reductions in 
User Fees (waiver guidance), sets out the criteria for each of these waivers.10  FDA evaluates 
requests for these waivers on a case-by-case basis.  
To reduce financial barriers to the development of these products, FDA has determined that any 
FDC or co-packaged drug product for the treatment of HIV that is listed in Attachment B of the 
fixed dose guidance will, for the foreseeable future, be considered to benefit the public health, 
because making these products available in the 15 countries that are the targets of the PEPFAR 
program will have a significant impact on the global efforts to treat HIV.    
 
Furthermore, for the foreseeable future, FDA will consider any FDC or co-packaged drug 
product for the treatment of HIV that is listed in Attachment B of the fixed dose guidance to be 
innovative because simplified regimens that will facilitate distribution and patient compliance, 
particularly in treatment naive patients, are needed in developing countries.  Therefore, FDA has 
determined that these products will meet the first part of the two-part PDUFA test for public 
health and barrier-to-innovation waivers.  At some point, after several alternative treatments have 
been made available, FDA may reevaluate whether these products remain innovative or whether 
a waiver for these products is necessary to protect the public health, and may find that, because 
of the existence of treatment alternatives, user fee waivers may no longer be appropriate.    
 
The second part of the test for granting a public health or barrier-to-innovation waiver is a 
financial test. That is, (1) a waiver of a user fee must be necessary to protect the public health, or 
(2) the assessment of the fee must be a barrier to innovation because of limited resources or other 
circumstances.  The statute gives FDA more discretion under the barrier-to-innovation test. 11  
Normally, a company with greater than $10 million in total annual revenue would not be found 
to have limited resources and would not be eligible for either a public health or a barrier-to-
innovation waiver.  However, FDA intends to consider the development of drugs for the 
PEPFAR program to be the sort of other circumstances that would justify a waiver of 
PDUFA user fees under the barrier-to-innovation waiver provision, provided the applicant 
meets all of the following conditions: 
 
                                                 
9 Section 736(d)(1)(A) and (B), 21 U.S.C. 379h(d)(1)(A) and (B). 
 
10 PDUFA also provides for a fees-exceed-the-cost waiver, in which the fees associated with all of an applicants 
submissions are compared with standard costs associated with FDAs reviews of the submissions and if the fees 
exceed the costs, the applicant gets a refund.  FDA does not believe this provision will provide a basis for waivers 
for PEPFAR participants but we are mentioning it for completeness.  For further information on this waiver see the 
guidance entitled Fees-Exceed-The-Cost Waivers Under the Prescription Drug User Fee Act. 
 
11 The statute does not provide FDA with the ability to consider other circumstances when determining whether to 
grant a public health waiver.  Accordingly, a company requesting a public health waiver will have to establish that it 
has limited resources to receive a public health waiver. 
  4 Contains Nonbinding Recommendations 
  The applicant is submitting an application for an FDC or co-packaged drug product for 
treatment of HIV from among the examples that are listed in Attachment B of the fixed dose 
guidance. 
  The applicant will only obtain a tentative approval in the United States for the product 
because, for example, it cannot market the product in the United States because of patents or 
exclusivity on the innovator product. 
  The applicant certifies that upon receipt of tentative approval for the product, the applicant 
will make the product available at competitive prices suitable for procurement under 
PEPFAR in one or more of the 15 designated PEPFAR countries.  FDA will accept 
certifications that are supported with one of the following:  (1) evidence that the product is 
being offered for procurement by PEPFAR, and (2) evidence that the product for which the 
application is being submitted has been approved for use by the government of one or more 
PEPFAR countries; or (3) if such approval has not been obtained, the FDC is listed on an 
HIV treatment guideline for one or more of the PEPFAR countries and the applicant provides 
a plan and schedule for the submission of an application for approval in one or more of the 
countries.   
 
To obtain a barrier-to-innovation waiver, applicants should submit a request for a waiver 45 days 
before an application will be submitted.  The waiver request should contain the certifications 
described above. 
 
B.  Annual Product and Establishment Fees 
 
PDUFA provides for annual user fees for certain prescription drug products and establishments.  
However, the following are not assessed annual user fees: 
 
1.  Products approved under section 505(b)(2) applications that are not assessed 
application fees because they are not for a new molecular entity or a new indication 
for a use 
2.  Products that are the same as another product approved under an application filed 
under section 505(b) or 505(j) of the Act  
3.  Products that are only tentatively approved 
 
If product fees are not assessed, the establishments in which such products are made are not 
assessed annual establishment fees, unless other fee paying products are made in the same 
establishment.  Therefore, a waiver would not be necessary for these product and establishment 
fees.  However, FDA intends to consider the development of drugs for the PEPFAR program 
to be the sort of other circumstances that would justify a waiver of PDUFA product and 
establishment user fees under the barrier-to-innovation waiver provision, provided the 
applicant meets all of the following conditions: 
 
  The applicant has obtained approval for an application for an FDC or co-packaged drug 
product for treatment of HIV from among the examples that are listed in Attachment B of the 
fixed dose guidance. 
  5 Contains Nonbinding Recommendations 
  The applicant certifies that it is making the product available at competitive prices suitable 
for procurement in one or more of the 15 designated PEPFAR countries.  FDA will accept 
certifications that are supported with one of the following:  (1) evidence that the product is 
being offered for procurement by PEPFAR and (2) evidence that the product for which the 
waiver is sought has been approved for use by the government of one or more PEPFAR 
countries; or (3) if such approval has not been obtained, the FDC for which the waiver is 
sought is listed on an HIV treatment guideline for one or more of the PEPFAR countries and 
the applicant provides a plan and schedule for the submission of an application for approval 
in one or more of the countries. 
  For establishment fees, no other user fee eligible products owned by the applicant are being 
manufactured at the establishment at which the PEPFAR product is being manufactured. 
 
The annual product and establishment fees are invoiced in mid-August with fees due to be paid 
by October 1 of each fiscal year.  We encourage applicants to submit requests for waivers of 
annual product and establishment fees by August 15 of each year. 
 
For information about how to request a waiver or reduction, please contact the user fee team in 
the Office of Regulatory Policy at 301-594-2041.  More information on user fees is available on 
the Internet at http://www.fda.gov/cder/pdufa/default.htm. 
 
  6 Contains Nonbinding Recommendations 
ATTACHMENT:  SUMMARY OF AVAILABLE EXEMPTIONS AND WAIVERS 
 
Table 1:  User Fee Exemptions  
 
Applications Not Assessed Fees or Assessed Reduced Fees: 
 
  Generic drug application submitted under 505(j) 
  Application submitted under 505(b)(2) if not (1) a new molecular entity or (2) a new indication for a use  
  Application that only requires BA/BE data will be assessed only 1/2 application fee 
 
Products Not Assessed Product Fees: 
  Tentatively approved product or product otherwise not approved 
  Product approved under section 505(b)(2) and is not assessed application fees  
  Products that are the same as another product approved under an application filed under section 505(b) or 
505(j) of the Act 
  If product is not assessed a fee, establishment in which it is made also not assessed a fee  
 
Table 2:  User Fee Waivers for PEPFAR Products 
 
Application Fees: 
 
  Small business waiver if:  <500 employees (with affiliates), and the first human drug application submitted 
to FDA by company (including affiliates) 
 
  Barrier-to-innovation waiver if:  
 
1.  Application for an FDC or co-packaged drug product for treatment of HIV from examples in the fixed 
dose guidance, 
2.  Only tentative approval in United States because, for example, of patents or exclusivity on the 
innovator product, and  
3.  Certification that product will be made available at competitive prices in one or more of the 15 
designated PEPFAR countries with supporting evidence. 
  
  Public health waiver if: 
 
1.  Application for an FDC or co-packaged drug product for treatment of HIV from examples in the fixed 
dose guidance, and 
2.  Total gross annual revenue of firm and affiliates <$10 million. 
 
Product and Establishment Fees: 
 
  Approval for FDC or co-packaged drug product for treatment of HIV from examples in the fixed dose 
guidance, 
  Certification that product will be made available at competitive prices in one or more of the 15 designated 
PEPFAR countries with supporting evidence, and 
  No other user fee eligible products owned by the applicant are being manufactured at the establishment at 
which the PEPFAR product is being manufactured. 
  7