Sec. 540.525 Scombrotoxin 
(Histamine)-forming Fish and Fishery 
Products  Decomposition and 
Histamine (CPG 7108.24) 
Draft Compliance Policy Guide 
 
Guidance for FDA Staff 
 
This draft compliance policy guide is being distributed for comment purposes only 
 
Additional copies are available from: 
Office of Food Safety, Division of Seafood Safety (HFS-325) 
Center for Food Safety and Applied Nutrition 
Food and Drug Administration 
5001 Campus Drive 
College Park, MD  20740 
(Tel) 240-402-2300 
https://www.fda.gov/inspections-compliance-enforcement-and-criminal-
investigations/compliance-manuals/manual-compliance-policy-guides 
 
Although you can comment on any guidance at any time (see 21 CFR 10.115(g)(5)), to ensure that FDA 
considers your comment on this draft guidance before we begin work on the final version of the 
guidance, submit either electronic or written comments on the draft guidance within 60 days of 
publication in the Federal Register of the notice announcing the availability of the draft guidance.  
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.  All comments should be identified with the docket number [insert docket number] listed in 
the notice of availability that publishes in the Federal Register.  
 
For questions regarding this draft document contact Steven Bloodgood, Division of Seafood Safety 
(HFS-325), Center for Food Safety and Applied Nutrition, 5001 Campus Dr., College Park, MD 20740, 
240-402-5316, email: steven.bloodgood@fda.hhs.gov. 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Office of Regulatory Affairs 
and 
Center for Food Safety and Applied Nutrition 
 
December 2021 
     
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
 
 
Table of Contents 
 
 
I. Introduction ............................................................................................... 3 
II. Background .............................................................................................. 3 
III. Policy ....................................................................................................... 5 
IV. Regulatory Action Guidance ................................................................. 5 
V. Specimen Charges .................................................................................... 7 
   
  2  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
 
Sec. 540.525 Scombrotoxin 
(Histamine)-forming Fish and Fishery 
Products  Decomposition and 
Histamine (CPG 7108.24) 
Draft Compliance Policy Guide 
 
Guidance for FDA Staff 
 
 
 
This draft compliance policy guide, when finalized, will represent the current thinking of 
the Food and Drug Administration (FDA or we) 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 the approach satisfies the requirements of the applicable statutes and 
regulations.  To discuss an alternative approach, contact the FDA staff responsible for 
this guide at the phone number listed on the title page.  
 
 
I. Introduction 
 
The purpose of this compliance policy guide (CPG) is to provide guidance for FDA staff 
on adulteration associated with decomposition and/or histamine identified during 
surveillance sampling and testing of fish and fishery products susceptible to histamine 
formation.  This CPG is being revised to update FDA regulatory action guidance for 
sensory analysis and histamine levels in scombrotoxin-forming fish and fishery products.  
 
The  contents of this document do not have the force and effect of law and are not meant 
to bind the public in any way, unless specifically incorporated into a contract.  This 
document is intended only to provide clarity to the public regarding existing requirements 
under the law.  FDA guidance documents, including this CPG, should be viewed only as 
recommendations, unless specific regulatory or statutory requirements are cited.  The use 
of the word should in FDA guidances means that something is suggested or 
recommended, but not required. 
 
II. Background 
 
The composition of the muscle tissue in certain fish species, such as tuna and mahi-mahi, 
can cause histamine, among other spoilage compounds, to form due to the activity of 
  3  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
enzymes produced by spoilage bacteria after the fish die.  Unless these particular fish are 
properly chilled promptly after death and maintained in a chilled state, or are otherwise 
treated or processed to prevent further microbial activity, histamine can accumulate in the 
edible muscle of these fish.  Once formed, histamine cannot reliably be removed by 
subsequent activities, such as washing, freezing, or heating.  
 
Properly harvested and handled fish and fishery products have little to no detectable 
histamine.  The presence of 35 ppm or more histamine in fish is evidence of considerable 
and avoidable time and temperature exposures resulting in microbial-induced 
decomposition (i.e., the conversion of histidine to histamine in the fish muscle by 
bacterial enzymes) whether or not the decomposition is detected by sensory 
examination.1  
 
Elevated histamine can be prevented in fish by adherence to Current Good Manufacturing 
Practices (CGMPs) (21 CFR Part 117, Subpart B) and Hazard Analysis Critical Control 
Point (HACCP) principles required by FDAs Fish and Fishery Products regulation (21 
CFR Part 123) by each processor in the distribution chain.  It is important to control the 
time and temperature of fish at each point in the distribution chain beginning with 
harvesters and the first receivers of fish from harvest vessels, along with the use of proper 
precautions by retailers and consumers.  Therefore, testing that reveals elevated histamine 
in FDAs surveillance samples is indicative of improper harvesting, processing, and/or 
storage of the sampled lot or shipment.  Additional information about scombrotoxin 
(histamine) formation in fish and the scombrotoxin hazard and its controls can be found 
in FDAs Fish and Fishery Products Hazards and Controls Guidance2 and FDAs Bad 
Bug Book.3 
 
In addition, scombrotoxin fish poisoning (sometimes also referred to as scombroid 
poisoning or histamine poisoning) continues to represent the highest number of illnesses 
associated with finfish in the United States.4  Adoption of a 200-ppm histamine level 
based on the possibility of human illness at or above that level is consistent with a 
conclusion of an international group of histamine and risk assessment experts convened 
by the Food and Agriculture Organization of the United Nations and World Health 
 
1 Staruszkiewicz, W.F., J.D. Barnett, P.L. Rogers, R.A. Benner, Jr., L.L. Wong, and J. Cook. 2004. Effects 
of on-board and dockside handling on the formation of biogenic amines in mahimahi (Coryphaena 
hippurus), skipjack tuna (Katsuwonus pelamis), and yellowfin tuna (Thunnus albacares). J. Food Prot. 
67(1):134-141.  
2  FDA. Fish and Fishery Products Hazards and Controls Guidance, Fouth Edition.  March 2020.  Available 
at:  https://www.fda.gov/food/seafood-guidance-documents-regulatory-information/fish-and-fishery-
products-hazards-and-controls. 
3  FDA.  Bad Bug Book, Foodborne Pathogenic Microorganisms and Natural Toxins. 2012.  Available at:  
https://www.fda.gov/food/foodborne-pathogens/bad-bug-book-second-edition.  
4 Centers for Disease Control and Prevention. 2017. Surveillance for Foodborne Disease Outbreaks. Annual 
Report. Available at: https://www.cdc.gov/fdoss/pdf/2017_FoodBorneOutbreaks_508.pdf. 
  4  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
Organization (FAO/WHO) and reported in 2013,5 and aligns the U.S. with other nations.6  
In addition, the Codex Alimentarius standards7 also identify 200 ppm as a health-related 
threshold.   
 
III. Policy 
 
FDA may regard scombrotoxin-forming fish or fishery products to be adulterated within 
the meaning of section 402(a)(1) of the Federal Food, Drug, and Cosmetic Act (FD&C 
Act) (21 U.S.C. 342(a)(1)) in that they bear or contain a poisonous or deleterious 
substance which may render them injurious to health, when histamine is present at or 
above 200 ppm, as established by testing.  
 
FDA may regard scombrotoxin-forming fish or fishery products to be adulterated within 
the meaning of section 402(a)(3) of the FD&C Act (21 U.S.C. 342(a)(3)) in that they 
consist in whole or in part of any filthy, putrid, or decomposed substance, when 
histamine is present at or above 35 ppm or when evidence of decomposition is detected 
by sensory analysis. 
 
FDA may regard scombrotoxin-forming fish or fishery products to be adulterated within 
the meaning of section 402(a)(4) of the FD&C Act (21 U.S.C. 342(a)(4)) in that they 
have been prepared, packed, or held under insanitary conditions whereby they may have 
become contaminated with filth, or whereby they may have been rendered injurious to 
health, when histamine is present at or above 35 ppm. 
 
IV. Regulatory Action Guidance 
 
The following regulatory action guidance is applicable to FDAs surveillance sample test 
results for all fish and fishery products that are associated with scombrotoxin (histamine) 
formation except dried fish and fermented fish sauce/paste products that are intended for 
use only as condiments or as minor flavoring ingredients in other food products.  Fish 
species associated with histamine formation and scombrotoxin (histamine) fish poisoning 
are listed in FDAs Fish and Fishery Products Hazards and Controls Guidance, Chapter 3, 
Table 3-2.  Decomposition in non-scombrotoxin-forming fish and fishery products is 
addressed in CPG Sec. 540.370 Fish and Fishery Products  Decomposition.8 
 
5  FAO/WHO [Food and Agriculture Organization of the United Nations/World Health Organization]. 
2013. Public Health Risks of Histamine and other Biogenic Amines from Fish and Fishery Products.   
Meeting Report.  Available at:  https://www.who.int/foodsafety/publications/histamine_risk/en/.  
6  For example, the European Commission has had this threshold since 2005.  See Commission Regulation 
No 2073/2005. 
7 See e.g., Codex STAN 36-1981, Standard for Quick Frozen Finfish, Uneviscerated and Eviscerated, 
Codex STAN 94-1981, Standard for Canned Sardines and Sardine-Type Products, Codex STAN 119-1981, 
Standard for Canned Finfish, Codex STAN 190-1995, Standard for Quick Frozen Fish Fillets; Codex 
STAN 236-2003, Standard for Boiled Dried Salted Anchovies, Codex STAN 244-2004, Standard for Salted 
Atlantic Herring and Salted Sprat. 
8 FDA.  CPG Sec. 540.370 Fish and Fishery Products  Decomposition.  2009.  Available at:  
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cpg-sec-540370-fish-and-
fishery-products-decomposition.  
  5  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
 
An appropriate ORA Program Field Office may initiate an enforcement action involving 
any of the violative situations described in the preceding section, provided at least one of 
the three following general requirements is met: 
 
A.  Decomposed  
 
An article of scombrotoxin-forming fish or fishery products meets criterion 1. or 2. 
(below)  
 
1.  Sensory evidence of decomposition 
 
Using a two-class, pass/fail evaluation approach, the presence of decomposition is 
detected in: 
 
a.  a minimum of two (2) subsamples from a lot when up to 30 subsamples 
are examined from the lot; or 
b.  a minimum of one (1) subsample from a lot when the lot consists of fewer 
than 30 units (fish or cartons of fish) and subsamples were collected and 
examined from all available units.  
 
The presence of decomposition is detected in a subsample, i.e., the subsample 
fails the decomposition evaluation, when: 
 
a.  20% or more of the edible portion, or portions/pieces within a subsample, 
contains definite and persistent sensory attributes indicative of 
decomposition; and/or  
 
b.  in the case of canned tuna, honeycombing of the tuna is observed; 
 
as determined by qualified FDA seafood sensory analysts (a current list of 
qualified FDA seafood sensory analysts may be obtained from ORA, Office of 
Regulatory Science). 
 
2.  Histamine levels as evidence of decomposition 
 
A histamine level equal to or greater than 35 ppm is detected by original and 
check analysis in one (1) or more subsamples from a lot when up to 30 
subsamples are analyzed from the lot.  The analytical method(s) identified for 
histamine detection in the applicable Compliance Program (CP) (CP 7303.842 or 
CP 7303.844) should be used.   
 
 
 
 
 
  6  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
B.  Bears or Contains a Deleterious Substance  
 
For an article of scombrotoxin-forming fish or fishery products, a histamine level 
equal to or greater than 200 ppm is detected by original and check analysis in one (1) 
or more subsamples from a lot when up to 30 subsamples are examined from the lot. 
 
The analytical method(s) identified for histamine detection in the applicable CP (CP 
7303.842 or CP 7303.844) should be used.   
 
Documented evidence of a scombrotoxin fish poisoning associated with an article of 
fish, irrespective of histamine content, should be reported to the Office of the 
Commissioners (OC) Office of Emergency Operations (OEO), and CFSANs 
Coordinated Outbreak Response and Evaluation Network (CORE).  
 
C.  Prepared, Packed, or Held Under Insanitary Conditions  
 
For an article of scombrotoxin-forming fish or fishery products, a histamine level 
equal to or greater than 35 ppm is detected by original and check analysis in one (1) 
or more subsamples from a lot when up to 30 subsamples are examined from the lot.    
 
The analytical method(s) identified for histamine detection in the applicable CP (CP 
7303.842 or CP 7303.844) should be used.   
 
Other Considerations 
 
The criteria in this guidance do not establish an acceptable level of decomposition or 
histamine in food.  Processors and owners of scombrotoxin-forming fish and fishery 
products are responsible for ensuring that the food complies with the FD&C Act.  FDA 
may choose to take regulatory action against adulterated food within the meaning of the 
FD&C Act that does not meet the direct reference criteria in this guidance. 
 
V. Specimen Charges 
 
Domestic Action 
 
A.  Decomposed 
 
The article of food was adulterated when introduced into and while in interstate 
commerce and is adulterated while held for sale after shipment in interstate 
commerce, within the meaning of section 402(a)(3) of the FD&C Act (21 U.S.C. 
342(a)(3)) in that it consists in whole or in part of a decomposed substance. 
 
B.  Bears or Contains a Deleterious Substance 
 
The article of food was adulterated when introduced into and while in interstate 
commerce and is adulterated while held for sale after shipment in interstate 
  7  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
commerce, within the meaning of section 402(a)(1) of the FD&C Act (21 U.S.C. 
342(a)(1)) in that it bears or contains a poisonous or deleterious substance, namely 
histamine, which may render it injurious to health. 
 
C.  Prepared, Packed, or Held Under Insanitary Conditions  
 
The article of food was adulterated when introduced into and while in interstate 
commerce and is adulterated while held for sale after shipment in interstate 
commerce, within the meaning of section 402(a)(4) of the FD&C Act (21 U.S.C. 
342(a)(4)) in that it has been prepared, packed, or held under insanitary conditions 
whereby it may have become contaminated with filth, or whereby it may have been 
rendered injurious to health.9   
 
Import Refusal 
 
A.  Decomposed 
 
The article of food is subject to refusal of admission pursuant to section 801(a)(3) of 
the FD&C Act (21 U.S.C. 381(a)(3)) in that it appears to be adulterated within the 
meaning of section 402(a)(3) of the FD&C Act (21 U.S.C. 342(a)(3)) in that it 
consists in whole or in part of a decomposed substance. 
 
B.  Bears or Contains a Deleterious Substance 
 
The article of food is subject to refusal of admission pursuant to section 801(a)(3) of 
the FD&C Act (21 U.S.C. 381(a)(3)) in that it appears to be adulterated within the 
meaning of section 402(a)(1) of the FD&C Act (21 U.S.C. 342(a)(1)) in that it bears 
or contains a poisonous or deleterious substance, namely histamine, which may 
render it injurious to health. 
 
C.  Prepared, Packed, or Held Under Insanitary Conditions  
 
The article of food is subject to refusal of admission pursuant to section 801(a)(1) of 
the FD&C Act (21 U.S.C. 381(a)(1)) in that it appears to be adulterated within the 
meaning of section 402(a)(4) of the FD&C Act (21 U.S.C. 342(a)(4)) in that it has 
been prepared, packed, or held under insanitary conditions whereby it may have 
become contaminated with filth, or whereby it may have been rendered injurious to 
health.9 
 
An import shipment offered for entry may be detained and subject to refusal if one or 
more like product forms of the same commodity in the entry appears to be adulterated  
(e.g., tuna sold as loins, saku blocks, steaks, cubes, poke, or ground; or one product form 
 
9 Note, the insanitary conditions led to a histamine level  greater than or equal to 35 ppm and may 
contribute to levels greater than or equal to 200 ppm if appropriate CGMPs and HACCP controls are not 
maintained. 
 
  8  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
packaged in varying product sizes such as tuna steaks packaged as individual 4 oz., 6 oz., 
and 8 oz. steaks). 
 
Issued: 10/1/80  
Reissued: 7/1/81  
Revised: 10/30/89, 3/95, 7/26/95, 5/2005, 11/29/2005, 12/23/2021 
  9