Contains Nonbinding Recommendations  
 Compliance Policy Guide  
Sec. 420.500 Interference with Compendial Tests  
Guidance for FDA Staff1  
You may submit either electronic or written comments regarding this guidance at any time. Submit 
electronic comments to http://www.regulations.gov. Submit written comments to the Division of 
Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, 
MD 20852. All comments should be identified with the docket number listed in the notice of availability 
that publishes in the Federal Register.  
For questions regarding this document contact the Center for Drug Evaluation and Research (CDER) at 
301-796-3100.  
Issued by:  
U.S. Department of Health and Human Services  
Food and Drug Administration  
Center for Drug Evaluation and Research  
Office of Compliance  
Office of Regulatory Affairs  
November 2012  
1 This guidance has been prepared by the Office of Compliance in the Center for Drug Evaluation and 
Research (CDER) and the Office of Strategic Planning and Operational Policy at the Office of Regulatory 
Affairs (ORA) at the Food and Drug Administration.  
2 Note that USP distinguishes between official articles, official products, and official substances. 
Here, the term, official product means a finished dosage form.  
Compliance Policy Guide  
Sec. 420.500 Interference with Compendial Tests  
This guidance 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 it 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 Compliance Policy Guide (CPG) provides guidance to FDA staff regarding compendial drugs for 
which added substances interfere with compendial assays or tests of the products. This CPG applies to 
drug products under the jurisdiction of the Center for Drug Evaluation and Research (CDER). A previous 
version of this CPG, numbered Section 420.500, published in FDAs Compliance Policy Guides Manual in 
1980. This CPG supersede that document.  
FDA's guidance documents, including this Compliance Policy Guide, 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  
Section 501(b) of the Federal Food, Drug, and Cosmetic Act states that a drug is deemed to be 
adulterated if it is recognized in an official compendium and its strength differs from, or its quality or 
purity falls below the standards set forth in the compendium. Under the Act, determination of strength, 
quality, or purity is made in accordance with the tests or methods of assay set forth in the relevant 
compendium.  
The United States Pharmacopeia (USP) indicates that certain added substances, excipients, and 
ingredients, such as antimicrobial agents, pharmaceutical bases, carriers, coatings, flavors, 
preservatives, stabilizers, and vehicles may be added to an official product to enhance its stability, 
usefulness, or elegance, or to facilitate its preparation, unless otherwise specified in the individual 
monograph. USP General Notices, Section 5.20.202. However, such added substances, excipients, and 
ingredients are not suitable for inclusion in an official article if they  
1 2  
interfere with the assays and tests prescribed for determining compliance with compendial standards. 
USP General Notices, Section 5.20.  
III. POLICY  
A compendial drug containing an added substance that interferes with the compendial assay or test of 
the product is adulterated under 501(b) of the Act.  
IV. REGULATORY ACTION GUIDANCE  
Regulatory action is indicated for adulterated compendial drugs when such products contain an added 
substance that interferes with the compendial assay or test of the product, even if the product is fully 
compliant under other methods of analysis.  
Revised: November, 2012