Guidance for Industry 
ANDAs:  Stability Testing of 
Drug Substances and Products 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
June 2013 
Generics 
 
   
Guidance for Industry 
ANDAs:  Stability Testing of 
Drug Substances and Products 
 
 
 
 
 
 
 
 
 
 
 
 
 
Additional copies are available from: 
Office of Communications 
Division of Drug Information, WO51, Room 2201 
Center for Drug Evaluation and Research 
Food and Drug Administration 
10903 New Hampshire Ave., Silver Spring, MD 20993  
Phone: 301-796-3400; Fax: 301-847-8714 
druginfo@fda.hhs.gov  
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
June 2013 
Generics 
 
   
 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION.............................................................................................................1 
II.  BACKGROUND...............................................................................................................1 
III.  DISCUSSION....................................................................................................................2 
   
 
1
Guidance for Industry  
ANDAs:  Stability Testing of Drug Substances and Products 
 
 
This guidance represents the Food and Drug Administrations (FDAs) 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 recommends that abbreviated new drug applications (ANDAs) submitted under  
section 505(j) of the Federal Food, Drug and Cosmetic Act, and the drug master files (DMFs) 
that support ANDAs, follow the stability recommendations provided in the International 
Conference on Harmonisation (ICH) stability guidances.     
 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the Agencys 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 
 
Over the past few years, the Office of Generic Drugs (OGD) has received numerous inquiries 
about what stability data FDA expects in ANDA submissions.  Currently, the only published 
direction from OGD is contained in a 1995 letter to industry which states that OGD will accept 
ICH recommended long-term room temperature conditions for stability studies (i.e., 252C, 
605% RH).  Although adequate in the context of other guidance existing at that time, this 
recommendation is no longer sufficient to serve as a basis for stability testing for ANDAs.   
 
The following existing ICH guidances address stability for new drug substances and products: 
 
1.  Q1A (R2) Stability Testing of New Drug Substances and Products. 
  
2.  Q1B Photostability Testing of New Drug Substances and Products. 
  
3.  Q1C Stability Testing for New Dosage Forms. 
 
                                                 
1 This guidance has been prepared by the Office of Generic Drugs, Office of Pharmaceutical Science in the Center 
for Drug Evaluation and Research (CDER) at the Food and Drug Administration.  
  1  
 
4.  Q1D Bracketing and Matrixing Designs for Stability Testing of New Drug 
Substances and Products. 
 
5.  Q1E Evaluation of Stability Data.2  
 
In the discussion that follows, these guidances are referred to as ICH stability guidances.   
 
III.  DISCUSSION     
 
Although the ICH stability guidances were developed by ICH to provide guidance on the 
information that should be provided in new drug applications to ensure the stability of new drug 
substances and drug products, we believe the recommendations also should be applied to 
ANDAs. 
 
When following the ICH stability recommendations, you, the applicant, should: 
 
1.  Submit data from three pilot scale batches or two pilot scale batches and one small 
scale batch.  If the size of the pilot scale batch does not follow ICH recommendations, 
the applicant should provide a justification. 
 
2.  At the time of submission, provide 6 months of data that include accelerated and 
long-term conditions.  FDA recommends following ICH guidelines with respect to 
utilization of intermediate conditions to support shelf-life. 
 
3.  Use multiple lots of drug substance as appropriate. 
 
4.  Manufacture and package the drug product using principles that are representative of 
the commercial process. 
 
5.  Provide a fully packaged primary batch. 
 
6.  Use drug product from all three primary batches when using bracketing and matrixing 
designs under ICH Q1D. 
 
7.  Provide statistical analysis of the data as appropriate, in accordance with ICH Q1E, 
Appendix A. 
 
If you choose not to follow the above recommendations, you should provide FDA with a 
justification for the approach you intend to follow in your ANDA submissions to ensure stability.   
                                                 
2 We update guidances periodically.  To make sure you have the most recent version of these guidances, check the 
FDA Drugs guidance Web page at 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. 
  2