Compliance Policy Guide  
CPG Sec. 280.100:  Stability 
Requirements - Licensed In Vitro 
Diagnostic Products  
 
 
Guidance for FDA Staff 
 
 
This guidance is for immediate implementation. 
 
 
 
 
FDA is issuing this guidance for immediate implementation in accordance with  
21 CFR 10.115(g)(4)(i).  Submit one set of either electronic or written comments on this 
guidance at any time.  Submit electronic comments to https://www.regulations.gov/.  Submit 
written comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.  You should identify all comments with 
docket number FDA-2020-D-1716.   
 
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 800-835-4709 or 240-402-8010, or email ocod@fda.hhs.gov, or 
from the Internet at https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-
regulatory-information-biologics/biologics-guidances.  
 
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 
July 2020  Contains Nonbinding Recommendations 
Table of Contents 
 
I.  INTRODUCTION: ........................................................................................................... 1 
II.  BACKGROUND: .............................................................................................................. 1 
III.  POLICY: ............................................................................................................................ 2 
IV.  REGULATORY ACTION GUIDANCE: ....................................................................... 2 
 
 
i 
  Contains Nonbinding Recommendations 
Compliance Policy Guide 
CPG Sec. 280.100:  Stability Requirements - Licensed In Vitro 
Diagnostic Products 
 
 
Guidance for FDA Staff 
 
 
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 Compliance Policy Guide (CPG) is to provide guidance to FDA staff on 
stability studies for in vitro diagnostic products (IVDs) licensed by the Center for Biologics 
Evaluation and Research (CBER).  
 
In general, 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 guidances means that something 
is suggested or recommended but not required.  
 
 
II.  BACKGROUND:  
 
In vitro diagnostic products may be approved or cleared through the medical device authorities 
of the Federal Food, Drug, and Cosmetic Act or licensed under the Public Health Service Act, 
depending on their intended use and active substances. Licensed IVDs must meet the 
requirements in the Quality System Regulation at Title 21 of the Code of Federal Regulations 
(CFR) Part 820, the provisions for in vitro diagnostic products in 21 CFR Part 809, the 
requirements in the biologics regulations at 21 CFR Parts 600-660, and the requirements in the 
approved biologics license application (BLA) for the particular product at 21 CFR Part 601. 
 
IVDs regulated as biological products are subject to a number of different provisions that pertain 
to stability testing prior to product approval.  The regulations for biological products require that 
data establishing the stability of the product through the dating period be included in the BLA 
(21 CFR 601.2(a)).  The IVD regulations, at 21 CFR 809.10(a)(5) and (b)(5)(iv), require that the 
1 
  Contains Nonbinding Recommendations 
 
product label and labeling include appropriate storage instructions which are based on reliable, 
meaningful, and specific test methods to protect the stability of the product1. 
 
 
III.  POLICY:  
 
CBER requires, as a condition of licensure, that stability studies must be conducted before the 
BLA for a new IVD product is approved to ensure it will meet the expiration dating and storage 
conditions stated on the label and labeling (21 CFR 601.2 (a) and (d)).  Post-approval stability 
studies generally are not required for licensed IVDs.  Exceptions to this may include: 
 
1.  Stability studies that are required as a condition of approval of the biologics license 
application; 
 
2.  Stability studies for products that have undergone changes or deviations in the 
manufacturing process or formulation changes (21 CFR 601.12(a)(2)); and 
 
3.  Stability studies that are indicated as part of a corrective and preventive action plan 
developed in response to a failure investigation conducted by the firm that would then 
support a previously established expiration date (21 CFR 820.100). 
 
 
IV.  REGULATORY ACTION GUIDANCE:  
 
Investigators may cite a licensed IVD manufacturer on a Form FDA 483 for failing to perform 
post-approval stability studies when:  (1) the manufacturer is required to perform the post-
approval studies as a condition of licensure; (2) the manufacturer has made a formulation or 
manufacturing change; or (3) the manufacturer has committed to perform post-approval stability 
studies as part of a corrective and preventive action plan.  Investigators should refer any 
questions regarding a firm's need to perform stability studies post-approval to CBERs Office of 
Compliance and Biologics Quality using the email CBERInspections@fda.hhs.gov. 
 
 
Issued:  8/14/2000 
Revised:  07/31/2020 
 
 
 
                                                           
1 The guidance issued by the Center for Devices and Radiological Health entitled Shelf Life of Medical Devices 
dated April 1991, provides some background information on the development of stability studies for device 
products.  https://www.fda.gov/media/72487/download 
 
2