[Federal Register Volume 64, Number 88 (Friday, May 7, 1999)]
[Notices]
[Pages 24664-24666]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-11318]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
[Docket No. 99N-1075]


Risk Assessment on the Potential Public Health Impact of Vibrio 
Parahaemolyticus in Molluscan Shellfish; Request for Scientific Data 
and Information

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; request for scientific data and information.

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SUMMARY: The Food and Drug Administration (FDA) is announcing a call 
for scientific data and information relevant to the agency's planned 
risk assessment on the potential public health impact of pathogenic 
Vibrio parahaemolyticus infections resulting from the consumption of 
raw molluscan shellfish. The risk assessment will assist FDA by 
providing a scientific framework for developing food safety policies 
relating to raw molluscan shellfish contaminated with pathogenic V. 
parahaemolyticus. FDA plans to hold public meetings to present the 
process of the risk assessment, to present information collected, and 
to allow interested parties additional opportunities to present data to 
facilitate this effort.

DATES: Submit scientific data and information by July 6, 1999.

ADDRESSES: Submit scientific data and information to the Dockets 
Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers 
Lane, rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Marianna D. Miliotis, Center for Food 
Safety and Applied Nutrition (HFS-327), Food and Drug Administration, 
200 C St., SW., rm. 3472, Washington, DC 20204, 202-205-4824, FAX 202-
205-4939, or e-mail ``[email protected].''
SUPPLEMENTARY INFORMATION:

I. Background

A. Vibrio parahaemolyticus

    V. parahaemolyticus is a gram-negative, halophilic bacterium that 
occurs naturally in estuarine environments and, therefore, can be 
present in many fishery products, including molluscan shellfish (Ref. 
1). The organism can cause acute gastroenteritis in consumers (Refs. 2, 
3, and 4), and in some individuals can also cause septicemia (Ref. 5) 
and even death (Ref. 6), though such cases have been reported only 
rarely. Worldwide, this organism is one of the leading causes of 
foodborne illnesses (Ref. 7). In the United States, the outbreaks 
caused by this organism usually have been associated with cooked crabs 
(Ref. 8), and illnesses transmitted by raw molluscan shellfish 
generally have been limited to sporadic cases (Ref. 9). However, in 
1997 V. parahaemolyticus from molluscan shellfish caused a large 
outbreak of illness involving a total of 209 individuals in the Pacific 
Northwest region, from California to British Columbia (Ref. 10). Many 
of these cases implicated oysters from specific growing areas, and the 
magnitude of this outbreak was considerably larger than

[[Page 24665]]

any previously caused by shellfish in the United States. In 1998, 
outbreaks caused by molluscan shellfish-borne V. parahaemolyticus 
occurred again, this time in three different coastal regions of the 
United States. Overall, more than 500 individuals from the Gulf Coast 
(Ref. 11), the Northeast (Ref. 12), and the Pacific Northwest (Ref. 13) 
reportedly became ill after consuming raw molluscan shellfish, and many 
of these cases were culture confirmed as attributable to V. 
parahaemolyticus.
    V. parahaemolyticus has been widely studied for years, and many of 
the factors influencing its pathogenicity and natural occurrence have 
been reported. For example, the organism is mesophilic, halophilic, 
grows optimally in alkaline pH, and causes illnesses and outbreaks 
principally during warmer weather months (Refs. 2, 5, and 14). However, 
those environmental factors and production practices that influence the 
incidence and prevalence of the organism and which would enable 
reliable estimates of risks associated with the consumption of seafood, 
especially molluscan shellfish, remain unknown.
    Investigations of both the 1997 and the June 1998 outbreaks 
demonstrated both epidemiological and direct relationships between 
illness and raw oyster consumption (Refs. 10 and 11). Moreover, 
accounts from some patients indicated that illness may result from the 
consumption of a single infected oyster, which suggests the possibility 
of a highly virulent strain, or a low infectious dose. A single 
serotype of V. parahaemolyticus, that being O3:K6, was identified as 
predominant in the June 1998 outbreak (Ref. 11). In September 1998, the 
same serotype of V. parahaemolyticus again was identified in a U.S. 
outbreak caused by raw oysters, this time in the Northeast region (Ref. 
12). Prior to 1998, with the exception of one isolated case in 1972 
(Ref. 15), serotype O3:K6 had been associated only with outbreaks in 
Asian countries (Japan, Bangladesh, Laos, and Taiwan) (Ref. 16). 
Notably, this serotype has repeatedly been associated with outbreaks, 
whereas most other serotypes are primarily associated with sporadic 
cases. For example, in Japan there were 43 V. parahaemolyticus 
outbreaks involving 1,131 patients during the summer of 1998. Thirty of 
the outbreaks (70 percent) were due to serotype O3:K6 (Ref. 16). Based 
on all information available, the Centers for Disease Control and 
Prevention (CDC) have described the O3:K6 serotype as ``an outbreak 
strain'' of V. parahaemolyticus, and FDA concurs with this current 
assessment. Other serotypes of the organism, such as O4:K8 currently 
seen predominantly in Japan (Ref. 17), may also merit special concern. 
FDA therefore believes that the U.S. outbreaks of illness in 1997 and 
1998 have identified certain serotypes of V. parahaemolyticus as 
important emerging pathogens linked to the consumption of raw molluscan 
shellfish, particularly oysters.
    However, since not all V. parahaemolyticus strains are 
enteropathogenic as determined by their ability to produce a 
thermostable direct hemolysin (TDH) (Ref. 18), FDA is concerned that 
determining the total concentration of this species in shellfish is 
unlikely to be useful for evaluating the risk of illness posed by V. 
parahaemolyticus. Other strain characteristics, such as invasion of the 
enterocytes (Ref. 19) and production of an enterotoxin (Ref. 20) may 
also be important to pathogenicity and thus useful in identification of 
pathogenic V. parahaemolyticus, other than the production of TDH.

B. Current Efforts

    FDA and the States share responsibility for the safety of molluscan 
shellfish for human consumption through the National Shellfish 
Sanitation Program (NSSP), a long-standing Federal/State cooperative 
program recognized by FDA for the sanitary control of molluscan 
shellfish produced and sold for human consumption. To promote safety, 
the NSSP has developed and maintained recommended shellfish sanitation 
control practices for adoption by member States. These control 
practices or guidelines are set out in the ``NSSP Guide for the Control 
of Molluscan Shellfish'' (Ref. 21) which also includes State growing 
area classification and dealer certification programs, and FDA 
evaluation of State shellfish control programs.
    In 1984, FDA entered into a Memorandum of Understanding (MOU) with 
the Interstate Shellfish Sanitation Conference (ISSC) recognizing the 
ISSC as the primary voluntary national organization of State shellfish 
regulatory officials that provides guidance and counsel on matters for 
the sanitary control of shellfish. The purpose of the ISSC is to 
provide a formal structure for State regulatory authorities to 
participate in establishing updated regulatory guidelines and 
procedures for uniform State application of the program. The ISSC has 
adopted formal procedures for State representatives to review shellfish 
sanitation issues and develop regulatory guidelines. Following FDA 
concurrence, these guidelines are published in revision of the NSSP 
guidelines mentioned above (Ref. 21).
    Historically, most illness caused by consumption of molluscan 
shellfish can be traced back to pathogens resulting from sewage 
contaminated water, and the NSSP has focused on control measures to 
prevent illnesses caused by pathogens that may occur in fecal material 
(Ref. 22). V. parahaemolyticus, however, occurs naturally in estuarine 
environments. Thus, there is uncertainty about the effectiveness of 
current NSSP measures to control V. parahaemolyticus in molluscan 
shellfish.
    In addition, FDA has previously indicated that V. parahaemolyticus 
in raw molluscan shellfish should not exceed a level of 10,000 cells 
per gram. This limit was based on data and reports from human volunteer 
studies (Refs. 2, 3, 14 and 23) conducted more than 25 years ago, and 
on investigations of U.S. outbreaks caused predominantly by cross 
contamination of cooked crabs (Ref. 8), which supported an estimation 
of minimum infectious dose of about 105  cells. However, the 
overall levels of V. parahaemolyticus found in oysters from harvest 
sites implicated during the 1997 and 1998 U.S. outbreaks suggest that 
the number of pathogenic cells required to cause illness is probably 
far less than previously believed, and it may be as low as 100 and 
1,000 cells. FDA now believes the 10,000 cells per gram level may be 
inadequate to protect the public health and did not rely on this level 
during the recent outbreaks. Instead, during the recent U.S. outbreaks, 
closing shellfish waters to harvesting was based on the occurrence of 
human illness. Reopening was based primarily on two factors: (1) Change 
in a season and/or conditions, particularly temperature, to those which 
historically have not been associated with illness, and (2) absence of 
the particular strains of V. parahaemolyticus associated with the 
outbreak. However, it is not certain that these measures are the most 
appropriate or effective.

II. Questions to be Considered by the Risk Assessment

    FDA is requesting scientific data and information that will allow 
it to respond to the following questions:
    1. What is the frequency of occurrence of pathogenic strains of V. 
parahaemolyticus in the shellfish waters? What parameters (e.g., water 
temperature, salinity, turbidity, and nutrient profiles) can be used as 
indicators of the presence of the organism in growing waters?

[[Page 24666]]

    2. What is the frequency of occurrence of pathogenic strains of V. 
parahaemolyticus in molluscan shellfish, and what are the numbers of 
viable pathogenic organisms at time of consumption? How are levels 
present in the bivalves at the time of consumption related to the 
initial levels in the growing waters?
    3. What is known about the dose-response relationship from 
outbreak, epidemiological, animal and other studies? What are the 
differences in dose-response relations among different strains and 
serotypes of V. parahaemolyticus, and among the different human 
susceptible subpopulations?
    4. What is the role of postharvest handling that may be influencing 
the numbers of V. parahaemolyticus in oysters? What reductions in risks 
can be achieved by intervention strategies such as depuration or 
relaying?
    5. What is the adequacy of current scientific knowledge, and where 
should future research be focused to reduce the uncertainty in the risk 
estimate?

III. Scope of the Risk Assessment

    Risk assessment is separate from risk management and risk 
communication. Thus, FDA's risk assessment will determine the 
relationships between molluscan shellfish, V. parahaemolyticus and 
illnesses; it will not determine an acceptable level of pathogenic V. 
parahaemolyticus.
    To accurately assess the exposure to pathogenic V. 
parahaemolyticus, the consumption of raw molluscan shellfish, 
especially oysters, will be considered. Exposure is a function of the 
V. parahaemolyticus prevalence in the shellfish and the consumption 
patterns of the population. The number of pathogenic V. 
parahaemolyticus in raw molluscan shellfish at consumption is the 
critical exposure information. Modeling will be used when V. 
parahaemolyticus data are collected during outbreaks, and at retail 
outlets to estimate actual exposure.
    The risk assessment will produce estimates of illness for levels of 
pathogenic V. parahaemolyticus likely to be consumed by different 
subpopulations. All assumptions and uncertainties will be identified 
and documented.
    FDA expects the risk assessment to provide the scientific 
underpinnings FDA needs to develop food safety policies that reduce the 
risk of disease resulting from ingestion of V. parahaemolyticus in 
molluscan shellfish, and other seafood consumed raw. Among other 
things, FDA anticipates that the data from the risk assessment will 
assist in determining the principal factors that should be considered 
in developing criteria for closing of shellfish waters to harvest in 
order to prevent illness and reopening waters after outbreaks of V. 
parahaemolyticus are over.

IV. Request for Data and Information

    FDA is requesting scientific data and information that will allow 
it to respond to the questions under section II of this document. The 
purpose of this request for data is to gather relevant information to 
facilitate a valid risk assessment of V. parahaemolyticus with the 
larger goal of providing a sound scientific basis for the food safety 
policies relating to raw molluscan shellfish contaminated with V. 
parahaemolyticus. FDA does not intend to utilize the submitted data and 
information to support future enforcement activity against seafood 
producers submitting the data. Accordingly, it is acceptable that data 
submitted in response to this notice be ``blinded'' in the sense that 
the data need not identify the particular seafood producer or processor 
that was the source of the samples underlying the results.
    Two copies of the scientific data and information are to be 
submitted, except that individuals may submit one copy. Scientific data 
and information should be addressed to the Dockets Management Branch 
(address above) and be identified with the docket number found in 
brackets in the heading of this document. Received materials may be 
seen in the Dockets Management Branch between 9 a.m. and 4 p.m., Monday 
through Friday.

V. References

    The following references have been placed on display in the Dockets 
Management Branch (address above) and may be seen by interested persons 
between 9 a.m. and 4 p.m., Monday through Friday.
     1. Roderick, G. E., M. A. Hood, and N. J. Blake, Medical 
Clinics of North America, 66:665-673, 1982
     2. Takikawa, I., Yokohama Medical Bulletin, 9:313-322, 1958.
     3. Aiiso, K. and K. Fujiwara, Annual Report of the Institute of 
Food Microbiology, Chiba University, 15:34-38 1963.
     4. Chai, T-J. and J. Pace, Goodborne Disease Handbook, p. 395 
to 425, Marcel Dekker, NY, 1993.
     5. Hlady, W. G. and K. C. Klontz, Journal of Infectious 
Diseases, 173:1176-1183, 1996.
     6. Hally, R. J., R. A. Rubin, H. S. Fraimow, and M. L. Hoffman-
Terry, Digestive Disease and Sciences, 1995.
     7. Olson, Jr., J. C., International Symposium on Vibrio 
parahaemolyticus, Saikon Publishing Co., Tokyo, pp. 259-261, 1974.
     8. Barker, W. H., Jr., Lancet, 1:551-554, 1974.
     9. Nolan, C. M. et al, Diagnostic Microbiology Infectious 
Disease, 2:119-128, 1984.
     10. CDC, Journal of the American Medical Association, 280:126-
127, 1998.
     11. Angulo, F., P. M. Griffin, and R. V. Tauxe, CDC, personal 
communication, 1998.
     12. CDC, Morbidity and Mortality Weekly Report, vol. 48, 1999.
     13. Sample, T. and M. Goza, FDA, personal communication, 1998.
     14. Sanyal, S. C. and P. C. Sen, International Symposium on 
Vibrio parahaemolyticus, p. 227 to 230, Saikon Publishing Co., 
Tokyo, 1974.
     15. Fishbein, M., B. Wentz, W. L. Landry, and B. MacEachern, 
International Symposium on Vibrio parahaemolyticus, p. 53 to 58, 
Saikon Publishing Co., Tokyo, 1974.
     16. Japanese National Institute of Infectious Diseases, 
Infectious Agents Survey Report, vol. 20, No. 1, 1999.
     17. Japanese National Institute of Infectious Diseases, 
Infectious Agents Survey Report, vol. 17, No. 7, 1996.
     18. Miyamoto, Y. et al., Journal of Bacteriology, 100:1147-
1149, 1969.
     19. Akeda, Y., K. Nagayama, K. Yamamoto, and T. Honda, Journal 
of Infectious Diseases, 176:822-824, 1997.
     20. Honda, T., M. Shimizu, Y. Takeda, and T. Miwatani, 
Infection and Immunity 14:1028-1033, 1976.
     21. ISSC and FDA, Guide for the Control of Molluscan Shellfish, 
U.S. DHHS, Washington, DC. p. 406, 1997.
     22. Fisher, L. M., Shellfish Sanitation, Public Health Reports 
No. 1178, U.S. Public Health Service, Washington, D.C., 1927.
     23. Doyle, M. P., Lancet, 336:1111-1115, 1990.

    Dated: April 29, 1999.
William K. Hubbard,
Acting Deputy Commissioner for Policy.
[FR Doc. 99-11318 Filed 5-6-99; 8:45 am]
BILLING CODE 4160-01-F