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FDA Consumer magazine
VOL. 29 NO. 10 DECEMBER 1995


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Features

How FDA Works to Ensure Vaccine Safety
Many dread diseases--such as smallpox, polio, rubella, and whooping
cough--have been eradicated or become rare, thanks to widespread
inoculation. But some people still have questions about the safety of
vaccines.

Concern About AIDS in Minority Communities
Rapid increases in HIV infection are occurring among minorities,
particularly in low-income urban African American and Hispanic
communities. The problem is often compounded by lack of access to health
care, cultural barriers to condom use, and denial. 

Botulinum Toxin: A Poison That Can Heal
Called the most poisonous substance known, botulinum toxin can paralyze
and kill if consumed in contaminated food. Now scientists have found a
way that it can be used, in a purified form, to treat certain muscle
conditions.

Fingernails: Looking Good While Playing Safe
High fashion for fingernail aficionados is not risk-free. Some chemicals
used to decorate nails can be poisonous and flammable if not used as
directed, and practices in some salons may encourage disease
transmission if regulations are not followed.

How Much Do You Know About FDA?
Does FDA regulate Spam? Insect repellent? Eye charts? Spaghetti? Take
this quiz and see if you can distinguish the products FDA regulates from
those it does not. 


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Departments



Updates 

The latest information on FDA-related issues, gathered from FDA Press
Releases, Talk Papers, and other sources.



Notebook 

A potpourri of items of interest gathered from the Federal Register and
other sources.



Investigators' Reports 

Selected cases illustrating regulatory and administrative actions--such
as inspections, recalls, seizures, and court proceedings--by FDA's
regional and district offices across the country



Summaries of Court Actions 

Cases involving seizure, criminal and injunction proceedings.




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How FDA Works to Ensure Vaccine Safety

by Isadora B. Stehlin

The gasping for breath and desperate hacking of whooping cough. The iron
lungs and braces of polio. Birth defects from rubella. For many people
today, those signs of terrible diseases are the stuff of history books,
thanks to vaccines. But the rare case of vaccine-associated polio or the
death of an infant soon after receiving a dose of pertussis vaccine may
make people wonder--are vaccines safe enough, or could they be safer?

For the Food and Drug Administration's Center for Biologics Evaluation
and Research (CBER), vaccine safety, along with effectiveness, is
central to regulation of these preparations. 

Clinical Trials

The first step to licensing a new vaccine is safety testing in animals.
If the laboratory animals immunized with the vaccine don't have serious
reactions, FDA consults with the vaccine manufacturer or sponsor on
further refining of the manufacturing process.

Because the weakened viruses used for vaccines are grown in animal or
human cells, "we spend a tremendous amount of time studying the safety
of those cells," says M. Carolyn Hardegree, M.D., director of CBER'S
office of vaccine research and review.

For example, the manufacturer of the recently licensed Varicella
(chickenpox) vaccine had to prove the human cell line used to grow the
virus was not contaminated with any other viruses, such as hepatitis.

Only after those studies have been done does testing in people begin.

FDA requires new vaccines to undergo several phases of clinical
trials--testing in people--for safety and effectiveness.

Phase 1 trials evaluate basic safety and identify only very serious or
very common adverse events. These trials are small--between 20 and 100
patients--and last just several months.

Phase 2 trials include several hundred patients and last anywhere from
several months to two years. This allows for more information on safety
and preliminary information on effectiveness to be collected.

Unless severe reactions or a lack of effectiveness surfaces during the
first two phases, the trials are expanded in Phase 3 to include several
hundred to several thousand people. These trials continue to measure
effectiveness and safety.

If, towards or at the end of the Phase 3 trials, the manufacturer
believes there are adequate data to show that the vaccine is safe and
effective for its intended use, the manufacturer applies to FDA for two
licenses--one for the vaccine (product license) and one for the
manufacturing plant (establishment license).

An internal FDA committee then reviews the clinical data, proposed
labeling, and manufacturing protocols that ensure a consistent product,
and the results of the agency's own confirmatory tests of the vaccine's
components and the final product. The review process includes an
inspection of the manufacturing facility. 

Advisory Committees

FDA advisory committees are groups of experts outside government that
review data and issues associated with products and recommend what
action the agency should take.

"Advisory committees may be brought in at any stage in the review
process," says Hardegree. "For example, before we went into Phase 1
trials of some of the first AIDS vaccines, we showed the [proposed
studies] to the Vaccines and Related Biological Products Advisory
Committee. As we move into determining what might be appropriate
efficacy studies, we might let them see that early on." Involving the
committees throughout the process is a good idea, she says, because
these expert advisors bring a wealth of scientific background to address
vaccine issues confronting FDA.

"Through the years, we've been very fortunate to have an outstanding
advisory group," says Hardegree. "We've had members who have been
willing to serve as consultants for many years after their four-year
term, and they provide a continuity on some of the issues that were
discussed years ago and are still being studied today."

Committee recommendations are not binding on FDA, but the agency
considers them carefully when deciding whether to license a vaccine for
marketing.

Green Light

Licensing of a vaccine is only the beginning of FDA's oversight.
Manufacturers must submit samples of each vaccine lot and results of
their own tests for potency, safety and purity to the agency before
release.

Each lot must be tested because vaccines are derived from living
organisms that are sensitive to environmental factors and are
susceptible to contamination.

"Tests generally applicable to all products include those for bacterial
and fungal sterility, general safety, purity, identity, suitability of
constituent materials, and potency," explains Hardegree. "Sterility
testing is performed on both bulk- and final-container material. In
addition, cell-culture-derived vaccines must be tested for
[disease-causing organisms]. All ingredients such as diluents,
preservatives or adjuvants must meet generally accepted standards of
purity."

The importance of these tests was established years ago. In 1955, the
virus-inactivated Salk polio vaccine first went on the market.
Unfortunately, virus in some batches of the vaccine produced by one
manufacturer was not totally inactivated, and some of the children who
got that vaccine developed polio. (See "Assessing Risks with Polio
Vaccines".)

Inadequate tests were the culprit, explains Hardegree.

The tests manufacturers must perform on each lot are spelled out in the
Code of Federal Regulations or in the product license application. When
the manufacturer sends the lot samples, along with the results of
testing, to FDA, "we either test the lot sample ourselves or go with the
manufacturer's documentation," says Jerome A. Donlon, M.D., Ph.D.,
director of CBER's office of establishment licensing and product
surveillance. With vaccines for diseases that attack the nervous system,
such as the live polio vaccine, "we test every lot because of the
tremendous potential for harm," he explains.

Over the last 10 years, there have been only three vaccine recalls. One
lot was recalled after FDA detected particulates; another was
mislabeled. The third lot was recalled because of potential problems
after an FDA inspection found violations of good manufacturing practices
at the production plant. 

Continuing Studies

Although clinical trials are carefully designed to uncover potential
adverse reactions before FDA licenses a vaccine, "we obviously can't get
all the information premarketing," says Susan Ellenberg, Ph.D., director
of CBER's division of biostatistics and epidemiology. "You're never
going to be able to do studies big enough to detect risks that might
happen at a level of one in 100,000 or one in 1 million. We'd never get
vaccines on the market. Still, such risks are important to detect
because of the large population exposed. So we have to develop
postmarketing surveillance programs."

For some vaccines, there are formal Phase 4 studies under way. At FDA's
request, the manufacturer of the new chickenpox vaccine, licensed by FDA
March 17, 1995, will monitor several thousand vaccinated children for 15
years to determine the long-term effects of the vaccine and possible
need for a booster immunization. (See "First Vaccine Available for
Chickenpox" in the September 1995 FDA Consumer.)

For most vaccines, the government relies on the Vaccine Adverse Event
Reporting System (VAERS) to identify problems after marketing begins.

FDA and the national Centers for Disease Control and Prevention manage
VAERS, a system the two agencies developed in response to the National
Childhood Vaccine Injury Act of 1986. Anyone--physicians, vaccine
manufacturers, patients, or the parents of a patient--can report to
VAERS an adverse event that may be associated with any vaccine.

"What we're most interested in with VAERS is identifying any new
problem, particularly serious problems, that might be so rare that it
wasn't noticed or detected during the clinical trials," says Ellenberg.

However, many events that might be associated with vaccines go
unreported.

"We don't have to have 100 percent reporting," says Donlon. Ellenberg
agrees. Still, she adds, "We need enough reports to permit detection of
rare events and to allow us to make reliable comparisons of reporting
rates among vaccine lots. Our ability to do this improves if doctors
make more reports and make them more timely."

Donlon points out that the report of an adverse event to VAERS is not
documentation that a vaccine caused the event. He says doctors shouldn't
make that judgment.

"Just report it," he says, "even if you've never seen it before. Maybe
many others around the country are seeing the same thing."

For example, a mother recently called FDA because her child's hair had
fallen out each time the child received a dose of the hepatitis B
vaccine. The mother said she asked the pediatrician whether the vaccine
could have caused the hair loss, but the pediatrician was sure that
couldn't be the case. In fact, after the second dose of the vaccine and
subsequent hair loss, the doctor was preparing to do a scalp biopsy to
determine the cause.

A search of the VAERS database found 45 cases of hair loss after
hepatitis B vaccination. Of those, 15 cases were like this one, in which
hair loss happened after each of two doses of the vaccine.

"That's called 'positive rechallenge,'" says Ellenberg, "and it gives
you a much stronger belief that the event was actually due to the
product. Now, hair falling out is not a life-threatening event. But if
people are aware it could happen, then they won't be imagining the
worst, and invasive, unnecessary tests may not have to be performed."

Besides identifying previously unknown adverse events, VAERS is an
important tool for monitoring individual lots of vaccines. "We don't
expect there to be problems with vaccine lots," says Ellenberg, "because
the regulations are very stringent. But even though we don't expect to
find anything, we look [at the reports to VAERS] every week, and if
there really was a problem with a lot, we could move very rapidly to get
that lot off the market.

"One of the first things we do if we see a lot that has an elevated
number of adverse events is look at its "sister" lots, the other lots
that came from the same larger bulk lot. If those lots also have high
rates of adverse events, it would raise our level of suspicion that
there might be a problem. If, however, the other lots had average or
even low rates, we would feel that this is just more likely chance
variation."

Another key factor to assess the significance of the number of adverse
events is the size of the lot.

"A lot with hundreds of thousands of doses is going to be associated
with more events than a lot with tens of thousands of doses," says
Ellenberg.

VAERS is designed to detect signals or warnings that there might be a
problem rather than to answer questions about what caused the adverse
event, according to "Research Strategies for Assessing Adverse Events
Associated with Vaccines," a 1994 report by the Institute of Medicine.
These signals can lead to hypotheses about causality, which can then be
tested by other methods, such as epidemiologic or laboratory studies. 

Background Rates Cause Confusion

"The problem with any vaccine that's given to very young children is
that there are a lot of background adverse events occurring in the first
year of life," says Ellenberg.

A reaction thought to be due to a vaccine may actually have been from
something else, such as an ear infection, explains Hardegree.

Children less than a year old are at greatest risk for high fevers,
seizures, and sudden infant death syndrome (SIDS). These events are seen
both in the presence and absence of vaccination. The SIDS death rate is
approximately 1.3 per 1,000 live births during the first year of life,
according to Ellenberg. During that same period, babies receive the DPT
vaccine three times--at 2, 4 and 6 months.

"You don't have to be a mathematician to appreciate the fact that, by
chance, SIDS will sometimes occur shortly after the vaccine was
administered," says Ellenberg. "The calculations that we have been able
to do suggest that the numbers of SIDS following vaccination that have
been reported to VAERS are not beyond what would be expected by chance.
And there have been some well-conducted, focused studies that
demonstrate that SIDS is not associated with DPT vaccination. But, on
the basis of VAERS data alone, we don't have proof that vaccines are not
contributing to these problems and we certainly don't have proof that
they are contributing."

Adding to the confusion is the fact that DPT is only one of many infant
vaccines. The recommended childhood immunization schedule (192K PDF
file) includes vaccines for hepatitis B, haemophilus b, measles, mumps,
rubella, and polio, all during the first 12 months.

At the other end of the age spectrum, deaths are also reported after
administration of the influenza vaccine. "Often these vaccines are given
to people in nursing homes," explains Ellenberg. Unfortunately, this
population has a relatively high death rate anyway, so it's almost
impossible to say whether a given death is associated with the vaccine,
she says.

As inevitable as some of those deaths, as well as other adverse events,
may be, FDA remains vigilant in its efforts to improve vaccine safety.
The agency will continue to be aggressive, says Hardegree, in its
efforts, along with manufacturers and other government agencies, to get
safer vaccines on the market. 

Isadora B. Stehlin is a member of FDA's public affairs staff. 
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Assessing Risks with Polio Vaccines

In 1955, the year the polio vaccine was licensed, an individual lot of
that vaccine infected 60 people directly and 89 who came in contact with
them because the manufacturer had failed to totally inactivate the
virus. But, as awful as that was, parents of other children weren't
deterred from having their children vaccinated.

"When a disease is rampant, the public will accept high-risk products,"
says Jerome A. Donlon, M.D., Ph.D., director of CBER's Office of
Establishment Licensing and Product Surveillance.

There have been no reported cases of paralysis caused by naturally
occurring polio virus in the United States since 1979. However,
according to the national Centers for Disease Control and Prevention's
Advisory Committee on Immunization Practices, about six to eight people
get polio from the live vaccine each year.

Unlike the vaccine-associated cases in 1955, these modern cases are not
caused by manufacturing failures. Instead, most of the cases are in
people with previously undetected immune deficiencies.

The problem is that the virus, though weakened, is still active. The
committee is developing a new polio vaccination policy that will include
a greatly enhanced role for inactivated (killed) polio vaccine. 

--I.B.S. 
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Developing New Pertussis Vaccines

Recent results of pertussis (whooping cough) vaccine clinical trials
show that three experimental vaccines are highly effective in infants.

The trials were sponsored by the National Institute of Allergy and
Infectious Disease, part of the National Institutes of Health, in
Bethesda, Md., and conducted in Italy and Sweden. The results also
showed that the experimental vaccines caused fewer side effects than a
vaccine currently used in the United States.

Scientists in FDA's Center for Biologics Evaluation and Research have
been instrumental in developing and evaluating acellular vaccines, such
as those tested in Italy and Sweden, and have collaborated with NIAID
and the vaccine manufacturers to design the European trials.

Acellular vaccines contain only the parts of the pertussis bacterium
thought to be important for immunity. U.S. vaccines licensed for use in
infants are called whole-cell vaccines, because they contain the whole,
inactivated pertussis organism.

Seizures were reported rarely in the trials, but no more frequently in
any of the pertussis vaccine groups than in the control group. Side
effects, such as redness, pain and swelling at the site of the
injection, fever, and protracted crying, were reported less commonly
with the acellular vaccines than with the whole-cell one.

FDA has made special efforts to encourage manufacturers to submit
applications for the use of acellular pertussis vaccines in infants. The
agency will target such applications for complete review within six
months of receiving them. However, actual times to any licensing can
vary, depending on the quality and completeness of the data submitted.

FDA recommends that parents continue to have their children vaccinated
against pertussis with available vaccines.

All vaccines pose some risks of side effects, but for both whole-cell
and acellular pertussis vaccines, serious, long-lasting problems are
extremely rare. Pertussis itself can be fatal. (For more information,
see "New Pertussis Vaccine Offers Prevention Alternative" in the
September 1992 FDA Consumer.) 

--I.B.S.

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Concern About 
AIDS in Minority Communities

by Alexandra Greeley

Although the spread of HIV seems to be relentless worldwide, and the
virus that causes AIDS now affects men, women and children of every age
and ethnic group, concern has been expressed that in this country,
certain groups may not be receiving adequate health care due to cultural
barriers.

Figures released from the national Centers for Disease Control and
Prevention in Atlanta show that as of Dec. 31, 1994, there have been a
total of 441,528 reported cases of AIDS in the United States since the
epidemic began, and about 1 million people are infected with the virus.
Although the number of new cases reported in 1994 (80,691) shows a
decline from 1993 (106,618), when CDC expanded the AIDS surveillance
case definition to include conditions--that is, opportunistic
infections--that happen earlier in the disease, they are higher than in
1992 (47,572).

Now, rapid increases in HIV infection are showing up among minorities,
specifically in the African American and the Hispanic communities. As
CDC's HIV/AIDS Surveillance Report of December 1994 states, "Among
reported cases, 1994 was the first year when blacks and Hispanics
together accounted for the majority (53 percent) of all cases reported
among men."

[Chart: Increase in Minority Percentage of Total AIDS Cases]

Data from the Centers for Disease Control and Prevention indicate that
in 1990, European Americans accounted for about 52 percent of AIDS cases
while African Americans made up about 30 percent and Hispanics about 17
percent. By 1994, the proportion of African American and European
American cases had become nearly equal: Europeans Americans made up
about 41 percent of AIDS cases and African Americans about 39 percent.
The Hispanic proportion rose to about 19 percent. (The chart on the
right can be selected as a 128K JPEG file.)

Infection rates are growing among the two other minority communities as
well--the Asian American/Pacific Islander and the Native American
(American Indian/Alaska Native) communities. According to CDC, of the
total reported new cases (including men, women and children) of AIDS in
1994, 33,193 were among European Americans (not Hispanic); 31,487 among
African Americans; 15,066 among Hispanics; 577 among Asian
Americans/Pacific Islanders; and 227 among American Indian/Alaska
Natives.

Minority groups, or "communities of color," have been, for reporting
purposes, classified into these four categories by the National
Commission on AIDS. According to the 1992 study, "The Challenge of
HIV/AIDS in Communities of Color" by the now disbanded commission,
members of each community share some physical characteristics or
ancestry. In addition, the study says, they also share the unfortunate
position of being society's underdogs, facing, historically, "broad,
sustained" racial discrimination. Other experts point out that those who
live in poverty of any ethnic background, including European American,
face the same kinds of problems accessing health care as do those
classified as racial or ethnic minorities. 

HIV's Spread Among Minorities

Even from the beginning of the epidemic, minorities were affected by the
virus, says the commission's study. In fact, says Helen Fox, senior
policy analyst, National Minority AIDS Council, Washington, D.C., there
has always been a higher incidence of HIV infection in communities of
color than early statistics indicated, because people used to assume
that AIDS was a gay white man's disease only and did not look for it
elsewhere. "There was no understanding of the disease or of the
relationship of injecting drugs and the transmission of the virus," she
says.

"Race and ethnicity are not risk factors," says Paul Denning, M.D.,
epidemiologist in CDC's AIDS Surveillance Branch. "But they are markers
for other factors that put people at increased risk, like lack of health
insurance and limited access to care."

Indeed, say Brenda Lee and Lyvon Covington, public health specialists in
the Food and Drug Administration's Office of AIDS and Special Health
Issues, a number of common factors, many economic ones, affecting many
minority groups contribute to the increase in AIDS: lack of medical
insurance, which results in a lack of access to health care; a higher
incidence of diseases or maladies in general; fear of medical care,
particularly among illegal aliens; limited or no means of transportation
to get to a health clinic; and for some, particularly in rural areas,
too few doctors. And even when doctors are available, having Medicaid
does not ensure adequate care, says Denning. "You may have Medicaid," he
says, "but many practitioners won't accept it."

Without routine medical care or testing, many people never suspect they
are infected with the virus, says Fox. "There is such a long incubation
period, and so many people feel pretty good," she says. "It is not until
they come down with some kind of infection or [for women] a yeast
infection that doesn't go away that they suspect something. Also people
may be sick, but without access to health care, they won't do anything
about it until they are very ill. Taking care of kids, housing and
work--these basic needs are more important than worrying about HIV."

In addition, for many women, condom use can be a major domestic issue.
Hispanic women, for example, often lack empowerment in sexual
relationships, says Ledia Martinez, Hispanic HIV/AIDS coordinator,
Office of HIV/AIDS Education, American Red Cross. "Women may not be able
to speak with their partners about condom use. ... Such conversations
are often interpreted as a sign that the female thinks the male is
unfaithful. So even if you are unsure of your man, but he is putting
food on the table, you risk losing him by pushing the condom-use issue.
You put that aside because it is more important that the kids have a
roof and that you are alive on a day-to-day basis." Besides, she notes,
most Hispanics are Roman Catholics, and the position of the Catholic
church, which opposes the use of condoms and other forms of
contraception, is another barrier against condom use.

And, Denning points out, many minorities live in the inner city or urban
areas, the foci of the epidemic. "Because the virus is very prevalent in
these communities, the chances or odds that a person's sexual partner
may be infected with HIV are increased," he says. "Also, one must
consider the fact that injection drug use and other substance abuse,
which are concentrated in disadvantaged, urban areas, have played a
major role in the spread of HIV. Injection drug use serves as a direct
mode of HIV transmission, while other substance abuse, like crack
cocaine use, may contribute to high-risk sexual behavior."

Some experts point to the "at-risk" factor as another reason why HIV has
spread rampantly, a factor that knows no community boundaries. "I think
the primary reason why people don't use protective measures--from
abstinence to condoms--is that they don't see themselves at risk," says
Owen McMaster, Ph.D., pharmacology toxicology reviewer, Center for Drug
Evaluation and Research, FDA. "They think they know their sexual
partner, or believe that this happens only to gay men who are not in a
mutually monogamous relationship, or they think that there is no way
that this beautiful, healthy-looking man or woman could have HIV."

Even understanding risk factors does not prevent risky behavior among
some minorities, points out Rafael Chang, prevention education director,
The Living Well Project, San Francisco. In a recent study of 260 gay
Asian Pacific Islander men, he says, the researchers found that many
people do understand the risk. "But they are not incorporating a sense
of worthiness and self esteem," he says, since they feel they do not
meet the American standard of beauty. As a result, he says, these men
take great risks by not practicing safer sex if their partner does meet
that standard of beauty. 

Barriers to Treatment

For minorities, discrimination, poverty, and inadequate health care and
education are barriers to meaningful prevention messages and to
treatment. And often, so are traditional beliefs.

Homophobia and the belief that AIDS is a gay, white man's disease have
helped both to spread and to hide the disease. First, many minorities
believe that the epidemic can't affect them or those in other
communities of color, says Cherylene Showell, executive director of
IMPACT (Intergroup Minority Project, AIDS Consortium and Trust) of D.C.
in Washington, so they ignore its threat. Second, when HIV strikes and
is associated with homosexuality, people deny its presence. This is true
in some African American communities, she says, where families often
hide and treat infected relatives as long as possible so outsiders
cannot suspect the presence of homosexuality.

And it is true in many Asian American communities, adds Fox, where AIDS
still often remains undiscussed and hidden and where many recent
immigrants believe that homosexuality brings shame on the family. Among
other immigrant populations, when men have sex with men, they do not
consider themselves gay, she says--and if the men become infected, it's
a real stigma.

"In most public health practices, once you know that there is something
dangerous, you let the community know," says Showell. "And they can take
whatever measures they need to protect themselves. But with HIV, people
don't treat it like the flu, because it is tied to all these 'isms'
[prejudices]." Instead, HIV becomes invisible with devastating results:
no awareness of HIV, increased infection rates, limited medical
treatment, and the spread of the epidemic. "It's really rather simple,"
she says. "I have seen this played out over and over again."

Other traditions provide roadblocks to medical care, too. In the
Hispanic population, for example, the community's language isolation and
culture may be part of the problem, according to Martinez. "Many
Hispanics live in their own communities and remain connected to each
other, but isolated from the mainstream," she says. "Even at school,
there might be an HIV curriculum, but it is not taught in Spanish, so
Hispanic children who speak only Spanish often never receive any
HIV-prevention messages."

Add to that the Hispanic view of life, their fatalism, she says. "It is
very common among Hispanics to feel that people are born with their own
cross to bear, and for some, having AIDS, or a son or sister with AIDS,
is the cross."

Among African Americans, the epidemic has provided a greater sense of
discrimination. "There is a denial [among African Americans] about the
origins of the disease," says Darlene Washington, African American
HIV/AIDS coordinator, Office of HIV/AIDS Education, the American Red
Cross. "The disease was associated with Africa, and immediately, people
said, `I won't believe this. They are always blaming us for bad things.
Why is Africa a deep, dark place of teeming germs?'"

But there is another level of denial, says Washington. The social,
sexual and drug implications of HIV at first caused some African
American faith communities to shy away from the issue, and as a result
its members shied away, too. However, says McMaster, many African
American congregations now do have HIV programs and are involved in HIV
ministries.

In addition, Washington and others believe that for African Americans,
the notorious 1970s Tuskeegee study, in which black men infected with
syphilis were studied but not treated, stirred a fear of mainstream
medicine. McMaster says this history seems to lead some African
Americans to believe that AIDS was created by scientists to get rid of
black people. "They think, 'If you made the disease to make me sick, why
should I trust you to cure me?'" he says. This distrust keeps people
from getting early treatment, from participating in clinical trials, and
from using experimental drugs.

Finally, some minorities still prefer traditional medicines--such as
herbs, massage, vitamins, and acupuncture--over Western medicines due to
uncertainty about side effects of some drugs, says Chang. "In the Asian
population, for example," he says, "there is a high rate of allergic
reactions to sulfa drugs. ... So if you have a community with a high
incidence of moderate-to-severe reactions, word gets out quickly, and
there is an unwillingness to participate in Western interventions." 

Federal Response to the Epidemic

Numerous private, corporate, community, state, and federal agencies are
trying to help stem the tide of HIV among minorities and assist and
support outreach and education programs. Federal agencies, in particular
can sustain broad prevention, research and education activities.

In its 1992 report, the National AIDS Commission recommended that
federal health educators learn and take into account the cultural
differences of minorities in order to target prevention messages
successfully. CDC is applying this strategy in its new community
collaboration and outreach efforts.

"We looked at the whole idea of communities and partnerships and
community planning," says Dorothy Triplett, assistant director for
Minority and Other Special Populations, Division of HIV/AIDS, CDC.
"Community leaders and state and local officials sit at the same tables
and are determining what the needs are," she says.

CDC is working with community gatekeepers to change risky behaviors and,
she says, CDC also funds national minority organizations and
community-based organizations. It has set up initiatives with the
Minority Health Professions Foundation, all African American medical
schools, and is working with the University of Puerto Rico.

At the National Institutes of Health in Bethesda, Md., which sponsors
AIDS clinical trials, officials are extending their efforts to enroll
minorities, which have historically been under-represented in trials and
treatment studies. According to George W. Counts, M.D., an infectious
disease specialist and director of the Office of Research on Minority
and Women's Health in NIH's National Institute of Allergy and Infectious
Disease (NIAID), it's important to make certain that trial results apply
to the minority population, and to make certain that experimental
therapies are equally available to minority groups.

To achieve these ends and to provide the best care to trial
participants, he says, NIAID aims to ensure equal access to clinical
trials and research programs and to dispel mistrust of those programs.
Minority enrollments in AIDS clinical trials rose from 17 percent of
enrolled subjects in 1988 to 44 percent in 1994.

FDA has developed and maintained numerous research and outreach efforts
in the AIDS fight. Says FDA's Mary Beth Jacobs, director, division of
life sciences, Center for Devices and Radiological Health, and the
center's AIDS coordinator, FDA focused immediately on condoms and their
testing and on fast-tracking the new Reality brand female condom as a
barrier to virus transmission. A new test method was developed in FDA
labs to evaluate barrier effectiveness for condoms and latex gloves. The
new Reality brand female condom was fast-tracked for approval.

Elsewhere in the agency, the Center for Drug Evaluation and Research
(CDER) actively facilitates the submission of investigational new drug
applications, uses treatment INDs and other mechanisms to make drugs
available as early as possible, and speeds the approval of AIDS drugs.

"We also send speakers to conferences to explain to researchers,
particularly those in minority communities, how to access the FDA," he
says. "While we have no minority-specific programs, FDA is making sure
that minorities are getting the information about how to get into
clinical trials and how to get experimental drugs." For example, a
special telephone line (1-800 TRIALSA) provides such information on an
ongoing basis.

"We also encourage sponsors to include a diverse population in their
clinical trials, but we have no specific regulatory requirement at this
time," he says. "In fact, both CDER and the FDA's Office of AIDS and
Special Health Issues give information to minority groups and minority
physicians about which pharmaceutical companies are doing clinical
trials so that minorities can enroll in the trials."

McMaster says that center officials are also studying the issue of
pharmacogenetics--that is, the way in which a person's genetic makeup
influences the efficacy of a drug and its side effects. The goal is to
determine if certain genetic groups may benefit more, or have fewer side
effects, when treated with certain classes of drugs. For example, such
studies have shown that African Americans respond better to certain
classes of antihypertensive drugs than to others. The hope is that
similar information could be obtained for AIDS drugs. The agency is also
meeting with representatives of other governments at the International
Conference on Harmonization to establish a single set of regulations
worldwide.

FDA's David Feigal, M.D., division director for antiviral drug
production in the center, says that FDA has responded in many ways,
including approving 20 different treatments in, "the fastest review time
of any group of products the agency has been responsible for."

As for the future? While many researchers and activists brace themselves
for the uphill fight ahead, Feigal feels that everyone must be committed
for the long haul. We can't wait for a vaccine, he says. Rather, victory
will come in little steps, as happened in the national effort to cut the
stroke rate among African Americans in the so-called "stroke belt" in
the South. "Broad-based community programs took screening and health
care into the black communities," he says. "So we need to do much of
this with HIV. This won't make the problem go away over night, but we
can chip away at it little by little." 

Alexandra Greeley is a writer in Reston, Va.

------------------------------------------------------------------------


Botulinum Toxin:
A Poison That Can Heal

by Luba Vangelova

Botulinum toxin can heal as well as harm. The bacterial toxin that can
paralyze and kill if consumed in contaminated food is now safely used,
in a purified form, as a medicine to control certain conditions marked
by involuntary muscle contractions.

The history and lethality of botulism would seem to make it an unlikely
source for a curative substance. Although death rates from botulism
poisoning are just a fraction of what they were 30 years ago, botulism
continues to strike dozens of people every year--most of them infants,
according to statistics from the national Centers for Disease Control
and Prevention in Atlanta.

"Botulism is still lurking, and if our guard is not up, it will create a
problem," says Richard C. Swanson, director of the Food and Drug
Administration's division of emergency and investigational operations
and one of the agency's representatives to the Inter-agency Botulism
Research Coordinating Committee.

Botulism-causing Clostridium botulinum bacteria and their spores are
everywhere. Prevalent in soil and marine sediments worldwide, their
spores are often found on the surfaces of fruits and vegetables, and in
seafood. The bacteria and spores themselves are harmless; the dangerous
substance is the toxin produced by the bacteria when they grow. There
are seven varieties of botulinum toxin, designated by the letters A
through G.

Botulinum toxin is "the most poisonous substance known," says Stephen S.
Arnon, M.D., head of the Infant Botulism Prevention Program at the
California Department of Health Services. For this reason, anyone with
symptoms of botulism should receive emergency treatment and public
health officials should be notified to locate the source of the
contamination and prevent other cases.

Once in the body, the toxin binds to nerve endings at the point where
the nerves join muscles. This prevents the nerves from signaling the
muscles to contract. The result is weakness and paralysis that descends
from the cranium down, affecting, among other things, the muscles that
regulate breathing.

Before the development of mechanical ventilators, the respiratory
paralysis caused by botulism claimed many more victims than it does
today. Between 1910 and 1919, for example, the death rate from botulism
was 70 percent. By the 1980s the rate had dropped to 9 percent, and in
1993 it was less than 2 percent. But recovery is still slow; assuming
the patient receives proper care to ensure continued breathing, recovery
occurs only when the affected nerves grow new endings, a process that
can take several months, although the length of time varies greatly from
case to case.

If botulism is caught in the early stages, injection of an antitoxin
made from horse serum can lessen the severity of disease by neutralizing
the toxin that has not yet bound to nerve endings. But because of the
risk of serious side effects such as anaphylaxis, a life-threatening
allergic reaction, and serum sickness (an unpredictable allergic
reaction to the horse serum, which can lead to anaphylaxis), the equine
antitoxin cannot always be used, and it is never given to infants.

The condition in which C. botulinum spores germinate and toxin is
produced--absence of oxygen, low acidity levels, and temperatures
between 40 and 120 degrees Fahrenheit (4.5 to 49 degrees Celsius)--can
easily develop in improperly stored home-cooked or commercial foods, as
well as in canned foods that have not been prepared with proper canning
procedures. Infant intestinal tracts, which haven't yet developed the
full range of beneficial bacteria, can also present an environment
inviting to C. botulinum toxin production, as can some deep wounds. 

Three Types

There are three types of botulism poisoning, distinguished by the manner
in which they are contracted: food-borne, wound and infant. In infant
botulism the toxin is produced when C. botulinum spores germinate in the
intestine. (Rarely, adults can acquire the disease this way.) In wound
botulism, which is very rare, the toxin is produced by C. botulinum
bacteria in an infected wound. In the food-borne form of the disease,
the person ingests the toxin itself by eating food contaminated with it.
Statistically, infant botulism, which was recognized in the mid-'70s, is
the most common form of the disease. But the public still generally
associates botulism with food poisoning in adults and children. The
food-borne disease is the most avoidable form of botulism.

Symptoms usually develop within a day of eating the food, although they
can take up to 10 days to manifest. Apart from weakness and paralysis,
common complaints include fatigue, dry mouth, and difficulty swallowing.
Unfortunately, doctors sometimes misdiagnose the symptoms as
Guillain-Barré syndrome, stroke, intoxication, or a handful of other
conditions. For this reason, federal health officials suspect that
botulism poisoning is underdiagnosed. 

Home Canning

One of the most common culprits in food-borne botulism is home-canned
food, especially vegetables such as asparagus, green beans, and peppers.
More than 90 percent of food-borne botulism outbreaks between 1976 and
1985 were due to home-processed foods.

[Picture illustrating proper temperatures for home canning]

"If you home-can products, make sure you use proper equipment, proper
containers to can in, and use the up-to-date process," Swanson advises.
U.S. Department of Agriculture home canning guidelines are available
from county extension offices. One basic recommendation is to cook food
to be canned in pressure cookers because they can maintain temperatures
high enough (above 212 F, or 100 C) for 10 minutes to kill the spores,
which are remarkably heat-resistant.

Foods cooked at home should not be left at temperatures between 40 F and
140 F (4.5 C to 60 C) for more than four hours. Toxin that may have
formed can readily be destroyed by boiling the food for 10 minutes.

Commercial foods have also been involved in botulism outbreaks. Some
outbreaks have been attributed to improperly handled food, such as
potato salad, served in restaurants. But many commercial food outbreaks
are due to consumer mishandling, such as disregarding labels that
indicate the food should be refrigerated. Some food companies acidify
their products or lower their moisture content as an extra precautionary
measure in case the refrigeration warning is not heeded. Consumers can
best protect themselves by reading the labels and following the storage
instructions, Swanson says, and by discarding rusty, swollen or
otherwise damaged cans. 

Infant Botulism

Infant botulism differs from food-borne botulism in that the toxin
itself is not ingested. Instead, C. botulinum spores swallowed by the
infant germinate and produce the toxin in the favorable environment of
the baby's large intestine.

Because the spores are nearly everywhere in the environment, children
and adults regularly ingest them, yet very rarely suffer ill effects. In
a few cases, adults who have had intestinal surgery or whose intestinal
tracts have otherwise been altered have contracted the disease the way
infants do. This has led researchers to conclude that infants' as-yet
"incompletely-developed intestinal flora," may be to blame, says Arnon,
one of the co-discoverers of infant botulism in 1976.

Infant botulism is serious, but rare and not usually fatal. From 1976
through the end of 1993, 1,206 infant botulism cases were confirmed in
the United States. About 75 to 100 cases are reported annually, about
half of them in California (presumed to be due to the prevalence of C.
botulinum spores in the state, its high number of births, and the
pediatric community's familiarity with the disease, which results in
more correct botulism diagnoses). All of the infant cases involve babies
less than 1 year old; the disease is most common in the second month of
life.

Infants' immature intestinal tracts offer a "window of vulnerability,
and if a baby has the bad luck to swallow a botulism spore during that
period, the spore has an opportunity to germinate," Arnon says. The
spores travel with microscopic dust particles, so the researchers have
concluded that most affected infants have simply inhaled the spores.
"They mix with saliva, they're swallowed, and that's how they reach the
intestine," Arnon says. Unfortunately, there is no way to prevent the
disease in such cases.

But parents and other caregivers can prevent babies acquiring infant
botulism from one source--honey. California researchers have isolated C.
botulinum spores from about 10 percent of store-bought honey samples,
and although less than 5 percent of infant botulism patients contract
the disease from honey, health officials and pediatricians agree that
honey should not be fed to infants under 1 year of age (it is perfectly
safe for older children and adults).

The first sign that an infant has botulism is usually constipation,
although this isn't always apparent to parents. Often the baby isn't
brought to a doctor until parents notice other symptoms, such as
lethargy and poor feeding as the paralysis begins to affect the baby's
gag reflex and swallowing ability.

Because breathing is affected in the most severe stage of
botulism-induced paralysis, researchers suspect a link between infant
botulism and sudden infant death syndrome (SIDS), also known as crib
death. One study done 15 years ago showed that about 5 percent of
children in California whose deaths were attributed to SIDS actually had
died from infant botulism. Because of the difficulty of conducting such
studies, the link between SIDS and infant botulism remains poorly
understood.

The infant botulism fatality rate is less than 2 percent, and recovery
is usually complete. Often, however, infants have to spend weeks or
months on a ventilator. Horse-derived antitoxin is not given to infants
because of the risk of side effects such as anaphylaxis and serum
sickness. But in February 1992, the California Department of Health
Services began a new clinical trial that may provide a way of lessening
the effects of the disease.

With funds from the FDA's Orphan Products Grants Program, the trial is
evaluating a human-derived antitoxin obtained from laboratory workers
who for occupational safety reasons have been immunized with botulinum
toxoid, which is toxin whose poisoning potential has been removed.

The California investigators will assess whether infants given the
antitoxin will have shorter hospital stays, fewer complications, and a
halt to the progression of disease. Infant botulism represents the only
opportunity to evaluate the safety and efficacy of human-derived
botulism antitoxin (known formally as Botulism Immune Globulin) because
of the sporadic and even less frequent occurrence of food-borne and
wound botulism. 

Use as Medicine

Meanwhile, purified botulism toxin is the first bacterial toxin to be
used as a medicine. FDA licensed botulinum toxin as Oculinum in December
1989 for treating two eye conditions--blepharospasm and
strabismus--characterized by excessive muscle contractions. It is now
marketed under the trade name Botox.

Small doses of the toxin are injected into the affected muscles. As
happens with botulism, the toxin binds to the nerve endings, blocking
the release of the chemical acetylcholine, which would otherwise signal
the muscle to contract. The toxin thus paralyzes or weakens the injected
muscle but leaves the other muscles unaffected. The injections "block
extra contraction [of the muscle] but leave enough strength for normal
use," says Barbara Karp, M.D., deputy clinical director of the National
Institutes of Health's National Institute of Neurological Disorders and
Stroke.

[Picture of woman taking Botox]

The effect of Botox is shown in the above photos. At left, a patient
with blepharospasm before injection with Botox is unable to open her
eyes due to abnormal muscle contractions. At center, still
pre-injection, she uses her fingers to keep her eyes open. At right,
after injection, her eyes stay open without difficulty. (Photos courtesy
Joseph Jankovic, M.D., professor of neurology, Baylor College of
Medicine, Houston, Texas)

Although the two eye conditions are the only indications for which it is
licensed, botulinum toxin has been used investigationally for a variety
of other conditions. "The main disease [group] the toxin is being used
for is dystonias--neurologic diseases involving abnormal muscle posture
and tension," Karp says. Examples include spasmodic torticollis
(contractions of the neck and shoulder muscles), oral mandibular
dystonia (clenching of the jaw muscles), and writers' and musicians'
cramps.

Other investigational uses include: spasmodic dysphonia (which results
in speech that is difficult to understand), urinary bladder muscle
relaxation (such as in cases where muscle contraction is severe enough
to require catheterized urination), esophageal sphincter muscle
relaxation, and the management of tics.

Experience shows that "it works better for some things than others,"
NIH's Karp says. For example, "it works better for disorders that
involve small muscles than large muscles," she says. But for about 2 to
5 percent of patients, the injections simply don't work at all, she
adds.

Injections usually have to be repeated, as the effects usually only last
about three to four months, although sometimes they can last over a
year. Because of this, up to 10 percent of patients eventually develop
antibodies to the toxin; this is more likely in patients who receive
higher doses at more frequent intervals. Therefore, the makers of the
biologic recommend that its dosage be kept as low as possible.

There are seven different types of botulinum toxin, and the currently
marketed therapeutic toxin is type A. NIH is studying whether patients
who have become immune to injections of type A toxin can successfully be
treated by toxins of other types. So far, the research indicates that
using type F to treat people with antibodies to type A seems to work,
Karp says.

Botulinum toxin has "an amazing safety record," says Bill Habig, Ph.D.,
the recently retired deputy director of FDA's division of bacterial
products in the Center for Biologics Evaluation and Research.
"Considering it's one of the most toxic materials known and there was a
lot of concern about it, it's turned out to be very safe," he says. 

Luba Vangelova is a writer in Takoma Park, Md. 
------------------------------------------------------------------------


Not for Wrinkles

Botulinum toxin type A has been promoted for use as a wrinkle remedy.
Apparently, some practitioners have been injecting the substance to ease
wrinkles by weakening face muscles. In a Nov. 18, 1994, Federal Register
notice, FDA denounced the promotion of such unapproved use as "an
egregious example of promoting a potentially toxic biologic for cosmetic
purposes."


------------------------------------------------------------------------


Fingernails:
Looking Good While Playing Safe

by Paula Kurtzweil

With the ease that comes from years of practice, Julie Le, of Nails R Us
in Alexandria, Va., sets out to remake customer Natalie Harris' nails.
She buffs, files, snips, clips, smooths, and then, with a nod from
Harris, paints on ruby red polish.

It's a process repeated every day throughout the country as thousands of
women like Harris--and men, too--strive for beautiful nails. They seek
the services of nail and beauty salons or manicure their nails
themselves with a host of nail products available on the market.

The reason, said Kim Siridavong, owner of Nails R Us, is simple:
"Everybody wants to look good."

But achieving that look is not without potential hazard. Infections and
allergic reactions can occur with some nail services and products. Some
chemicals in nail products, if ingested, are poisonous. Many are
flammable.

Relying on nail and beauty salons is not risk free, either. They use the
same products, and they may present a greater risk for disease
transmission.

Federal and state regulations help reduce the risks, but consumers also
need to take care that their pursuit of beautiful nails ensures healthy
nails. 

Growth of an Industry

[Picture: 1993-1995 Market Projections for Salons' Top Nail Services]

With the increased use of nail services and products in recent years has
come growing concern about safety. According to Nails 1995 Fact Book,
U.S. consumers will spend an estimated $5.2 billion on nail services in
1995, half a billion more than in 1994. They can choose from 34,852
freestanding nail salons across the country--nearly 2,000 more than a
year ago--or hundreds of thousands of beauty salons that offer nail
services.

The most requested service, according to the Fact Book, is artificial
nails. Manicures are No. 2. Other popular services include nail jewelry
and nail art.

Because of the variety of nail services, the preferred term for a person
who provides nail services is "nail technician" rather than manicurist,
said Suzette Hill, managing editor for Nails, a magazine for
professionals and students.

"Twenty years ago, they mainly did manicures," she said. "Now, they're
doing so much more."

They use a range of products, including polishes, paints, artificial
nails, glues, and laminates, many of which are available for home use,
too. 

Nail Products as Cosmetics

Nail products for both home and salon use are regulated by the Food and
Drug Administration. Under the Federal Food, Drug, and Cosmetic Act,
these products are considered cosmetics because they are "articles other
than soap which are applied to the human body for cleansing,
beautifying, promoting attractiveness, or altering the appearance." (See
"Cosmetic Safety: More Complex Than at First Blush" in the November 1991
FDA Consumer.) 

By law, nail products sold as cosmetics in the United States must be
free of poisonous or deleterious substances that might injure users
under the usual or customary conditions of use intended by the
manufacturer. These uses are printed on the package or on a package
insert. Many nail products contain poisonous substances, such as
acetonitrile in glue removers, but are allowed on the market because
they are not harmful when used as directed. They're poisonous only when
ingested, which is not their intended use.

Products sold for home use also must be labeled properly, with the names
of the ingredients listed in descending order of predominance. (See
"Decoding the Cosmetic Label," originally printed in the May 1994 FDA
Consumer.)

FDA does not review or approve nail products and other cosmetics before
they go on the market. However, the agency inspects cosmetic
manufacturers and samples and analyzes cosmetics as needed. If a safety
problem arises, the agency can take legal action against the product.

FDA also tracks safety problems through its Cosmetic Voluntary
Registration Program, in which cosmetic manufacturers voluntarily report
to FDA the types of adverse reactions their customers have reported to
them. FDA uses this information to determine a baseline reaction rate
for specific product categories, such as cuticle softeners, nail
extenders (artificial nail ends), and nail polishes. The agency gives
this information to participating companies so they can compare their
adverse reaction rates to FDA's determined baseline.

FDA also learns about potentially harmful products from manufacturers'
competitors, consumers, doctors, and nail technicians, who report
adverse reactions directly to the agency. 

Salon Safety

The salons and their technicians are regulated by the states, usually
their cosmetology boards. Lois Wiskur, past-president of the National
Interstate Council of State Cosmetology Boards, said that as far as she
knows, every state has some type of licensing requirements for nail
salons, nail technicians, or both.

Under these requirements, salons providing nail services usually must
meet certain requirements, such as:

 * Employing nail technicians who have had a minimum number of hours of
classroom and practical training.

 * Properly sterilizing manicure implements. The preferred methods are
autoclaving (heat sterilization) or chemical sterilization.

 * Undergoing a state inspection periodically.

 * Maintaining sufficient equipment, such as at least one manicure table
and one sink that runs hot and cold water.

 * Making sure that employees wash their hands before beginning work on a
customer.

To prevent blood-borne infections, such as HIV and hepatitis, the
national Centers for Disease Control and Prevention recommended similar
sanitary practices for salon employees in guidelines issued in 1985. The
guidelines targeted, among others, personal-service workers, such as
manicurists and pedicurists. To date, there have been no reports of
transmission of blood-borne diseases to or from a personal service
worker, according to CDC. 

Nail Infections

More common nail problems, dermatologists report, are infections from
bacteria, such as Staphylococcus; fungi, such as Candida (also known as
yeast); and skin viruses, such as warts.

Bacterial and fungal infections frequently result from artificial nails,
whether applied at home or in a salon. A bump or knock to a long
artificial nail may cause it to lift from the natural nail at the base,
leaving an opening for dirt to get in. If the nail is reglued without
proper cleaning (with rubbing alcohol, for example), bacteria or fungi
may grow between the nails and spread into the natural nail.

Also, as the natural nail grows, an opening develops between the natural
nail and artificial nail. If this space is not filled in regularly, it
can increase the chances for infection.

A fungal infection can take hold when an acrylic nail is left in place
too long--such as three months or more--and moisture accumulates under
the nail.

Bacterial, fungal and viral infections also can occur from using
insanitary nail implements, especially in a salon, where the same
implements are used on many people.

Unclean implements are especially dangerous if the skin around the nail
is broken. This can occur with overzealous manicuring--if, for example,
too much of the cuticle is cut or pushed back too far. If the cuticle is
cut or separated from the fingernail, infectious agents can get into the
exposed area. This is why dermatologists recommend leaving cuticles
intact.

Symptoms of an infection include pain, redness, itching, and pus in or
around the nail area. Yellow-green, green, and green-black nail
discolorations are signs of a Pseudomonas bacterial infection. A
blue-green discoloration signals a fungal infection.

If an infection appears while wearing artificial nails, they should be
removed and the area cleaned thoroughly with soap and water. If symptoms
persist, the person should consult a doctor, who may prescribe a topical
or oral anti-infective medicine.

There are no approved nonprescription products to treat fungal nail
infections, and over-the-counter products to treat other types of fungal
infections should not be used for nail infections. In a review of OTC
antifungal products, FDA found that fungal infections of the nails
respond poorly to topical therapy, partly because of the nail's
thickness. So, in 1993, the agency ruled that any OTC product labeled,
represented or promoted as a topical antifungal to treat fungal
infections of the nail is a new drug and must be approved by FDA before
marketing. This rule, which went into effect in 1994, does not include
prescription antifungal products.

Despite the rule, some companies continue to sell unapproved OTC nail
products, such as nail glues, with antifungal claims. FDA has warned
these companies it might take legal action if they don't stop selling
the products. 

Allergies and Other Hazards

Other common problems associated with nail products are allergic
reactions, such as contact dermatitis, a skin rash characterized by
redness and itching and sometimes tiny blisters that ooze. (See "Contact
Dermatitis: Solutions to Rash Mysteries" in the May 1990 FDA Consumer.)

Certain nail ingredients are known for their tendency to cause allergic
reactions. Residual traces of the basic building blocks of acrylic
resins ("acrylics") used in artificial nails, for example, can cause
redness, swelling and pain in the nail bed. In some cases, the reaction
is so severe that the natural nail separates from the nail bed, and
although a new nail usually grows in, it may be imperfect if the nail
root has been damaged.

Nail strengtheners that contain "free formaldehyde" may cause an
irritation or reaction, as can certain other chemicals in nail glues and
polishes.

In the late 1970s, use of methyl methacrylate, then a common ingredient
in artificial nail products, resulted in FDA receiving a number of
reports of injuries and allergic reactions, including damage and
deformity of fingernails and contact dermatitis. The ingredient now is
rarely used because of legal action against a former manufacturer of
methyl methacrylate-containing products and numerous seizures and
recalls of such products. Methyl methacrylate has since been replaced
with other chemicals, such as ethyl methacrylate. However, according to
John Bailey, Ph.D., acting director of FDA's Office of Cosmetics and
Colors, the replacement chemicals have never been fully studied for
safety, and they may be as harmful as methyl methacrylate.

"Our current guidance is that products containing ethyl methacrylate
should be used only by trained nail technicians under conditions that
minimize exposure and skin contact because of their potential to cause
allergies," he said.

Whatever the cause, allergic reactions usually take place where the
product has been applied or where it has inadvertently come in contact
with other skin surfaces, such as the face, eyelids and neck.

When the offending agent is no longer used, reactions clear up.
Sometimes, the user can identify the chemical causing the allergic
reaction and avoid it.

Though rare, some nail products can cause illness and even death,
particularly if ingested by children. In 1987, a 16-month-old toddler
died of cyanide poisoning after swallowing a mouthful of solvent used to
remove sculptured artificial fingernails. At least one other youngster
was rushed to the emergency room for intensive care after swallowing a
similar product. These products contained acetonitrile, a chemical that
breaks down into cyanide when swallowed. Since 1990, the Consumer
Product Safety Commission has required household glue removers
containing more than 500 milligrams of acetonitrile in a single
container to carry child-resistant packaging. This includes glue
removers for artificial nails. 

Nail products also can be dangerous if they get in the eyes. And they
can easily catch on fire if exposed to the free flame of the pilot light
of a stove, a lit cigarette, or even the heating element of a curling
iron.

Consumers should read labels of nail products carefully and heed any
warnings. 

Healthy Nails

From current consumer habits, one might surmise that the main function
of nails is to look good. But nails serve several physiological
purposes: They enhance fine touch and fine motor skills and protect the
fingers and toes. Doctors also may examine them for indications of
serious underlying diseases; for example, clubbed nails (a condition in
which fingers or toes thicken and the nails wrap around them) is a
classic sign of chronic lung and heart disorders. For those reasons,
it's important to keep nails healthy.

With proper care and precautions, nails can be both healthy and
attractive. 

Paula Kurtzweil is a member of FDA's public affairs staff.
------------------------------------------------------------------------


Precautions for Artificial Nails



 * If there is any question about sensitivity to the materials in artificial nails, have one nail done as a test and wait a few days to see if a reaction develops.

 * Never apply an artificial nail if the natural nail or skin around it
   is infected or irritated. Let the infection heal first.

 * Read the directions for do-it-yourself nails before applying them,
   and follow the directions carefully. Save the ingredient list for your
   doctor in case you have an allergic reaction or other injury.

 * Treat your artificial nails with care. They may be stronger than your
   own, but they still can break and separate. Try not to bump or knock
   them. Find new ways to do ordinary tasks, like using a pencil to dial or
   depress the numbers on the phone.

 * If an artificial nail separates, dip the fingertip into rubbing
   alcohol to clean the space between the natural and artificial nails
   before reattaching the artificial nail. This will help prevent
   infection.

 * Never use household glues for nail repairs. Use only products
   intended for nail use, and follow directions.

 * Don't wear artificial nails for longer than three months at a time.
   Remove them for one month to give nails a rest.

 * Keep nail glues and other poisonous substances out of the reach of children.

--P.K.


------------------------------------------------------------------------


Selecting a Safe Nail Salon

To help you decide if a salon provides sanitary nail services, nail and
public health experts suggest considering the following:

 * Is the salon licensed? Licenses often are posted. If you don't see
one, ask.

 * Are the nail technicians licensed? These licenses also are usually
posted. Ask if you don't see one for your technician.

 * How are nail implements sanitized? Autoclaving (heat sterilization)
   is best, says Ralph Daniel, M.D., a dermatologist in Jackson, Miss. But
   most states allow chemical sterilizing as long as the implements are
   immersed in the solution for at least 10 minutes between customers. Ask
   the technician what the salon's practices are. If they're using a
   chemical solution, check the product's label for words like "germicidal"
   to indicate that it is strong enough to kill bacteria. If in doubt,
   bring your own implements, Daniel suggests.

 * Is there a pre-service scrub? Both the nail technician and the client
   should wash their hands with an antimicrobial soap before nail work
   begins.

 * Is each customer given a fresh bowl of soapy water to soak their
   nails in and is a new nail file used for each customer? Both practices
   should be followed.

 * Is the facility neat and clean? Paul Kechijian, M.D., a clinical
   associate professor of dermatology and chief of the nail section at New
   York University, compares selecting a salon to selecting a restaurant.
   "Ask yourself when you walk in: Would you want to eat there?" he says.

 * Is there a strong smell of fumes? If there is, it's a sign that the
   facility is poorly ventilated, says John Bailey, Ph.D., acting director
   of FDA's Office of Cosmetics and Colors. Inhaling the fumes from nail
   products can make you sick.

If you have a complaint about a salon providing nail services, contact
your state board of cosmetology.

--P.K.


------------------------------------------------------------------------


Reporting Adverse Nail Product Reactions

Doctors, nail technicians, and consumers should report adverse reactions
from nail products to the nearest FDA office, listed in the blue section
of the telephone book. Or, write to:

Food and Drug Administration
Center for Food Safety and Applied Nutrition 
Office of Cosmetics and Colors (HFS-100)
200 C St., S.W.
Washington, DC 20204

------------------------------------------------------------------------


How Much Do You Know About FDA?

The Food and Drug Administration regulates a large number of consumer
products--but not everything! How good are you at distinguishing which
products FDA regulates from those it doesn't? Take this quiz--put
together by Bernie Janiger of FDA's New York district office--and see.

Circle the one item in each of the following groups that is not under
the jurisdiction of the Food and Drug Administration. Answers follow.

Question l:
a. Spam
b. puppy food
c. chocolate-covered cherries
d. frozen spinach
e. imported caviar

Question 2:
a. aspirin
b. anti-lice shampoo
c. insect repellent
d. eye shadow
e. lipstick

Question 3:
a. pesticide residues in lettuce
b. canned tomatoes
c. oven cleaner
d. spaghetti
e. pet turtles

Question 4:
a. airport security x-ray machines
b. laser products used in lumber mills
c. magnetic resonance imaging (MRI) diagnostic equipment
d. smoke detectors
e. microwave ovens

Question 5:
a. TV sets
b. over-the-counter antacid
c. TV ads for aspirin
d. diphtheria, pertussis and tetanus vaccine
e. human plasma

Question 6:
a. baby pacifiers
b. baby bottle nipples
c. ceramic ware for food use
d. coffee mugs
e. eye chart

Question 7:
a. illegal heroin use
b. veterinary tetracycline
c. barbiturates
d. medicinal oxygen
e. methadone

Question 8:
a. kidney dialysis machine
b. tongue depressor
c. toothpaste
d. fluoridated toothpaste
e. hair dryer

Question 9:
. a. label on beer
b. ground coffee
c. coffee beans
d. rabbit meat
e. canned tuna

Question 10:
a. home canning equipment
b. food warehouse
c. drug warehouse
d. hearing aid dispenser (retailer)
e. exporting of drugs

Question 11:
a. Halloween make-up
b. theatrical make-up
c. soap
d. eye mascara
e. nail polish

Question 12:
a. vaccine for horses
b. penicillin for horses
c. medicated feed for hogs
d. pet parrots
e. bird feed

Question 13:
a. tap water
b. club soda
c. bottled mineral water
d. ginger ale
e. bottled water for water cooler

Question 14:
a. tamper-resistant packaging for over-the-counter (OTC) drugs
b. child-proof packaging for OTC drugs
c. plastic containers for soft drinks
d. valentine heart containing chocolates
e. a tube containing medical ointment

Question 15:
a. grooming cream for dogs
b. artificial limb for dogs
c. laser scanner at supermarket checkout
d. mercury vapor lamps
e. vitamin C tablets


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Quiz Answers and Explanations

1. Answer a: Spam is a meat product. The U.S. Department of Agriculture
is responsible for regulating meat (and poultry) products.

Caviar, and all seafood and seafood products, whether imported or
domestically produced, are regulated under the Federal Food, Drug, and
Cosmetic Act (FD&C Act) as a food. So, too, are the other choices.

2. Answer c: Insect repellents are regulated as pesticides by the
Environmental Protection Agency.

Both aspirin and shampoos that get rid of lice are drugs; eye shadow and
lipstick are cosmetics; all are regulated by FDA.

3. Answer c: Oven cleaners are regulated by the Consumer Product Safety
Commission.

Canned tomatoes and spaghetti are regulated as foods by FDA. Tolerances
for pesticide residues in foods are established by EPA, but FDA is
responsible for ensuring that these tolerances are not exceeded on foods
(except for meat, poultry and certain egg products, which are under
USDA's jurisdiction). A tolerance level is the maximum amount of a
pesticide residue permitted in or on a food. FDA enforces a ban on the
sale and distribution of turtles less than 4 inches long, the size most
often sold as pets. Pet turtles frequently carry Salmonella bacteria,
which may cause severe diarrhea in children and adults. Baby turtles
were sold as pets in the United States until 1975, when the national
Centers for Disease Control and Prevention determined that the bacterial
contamination could not be prevented by any known treatment. 

4. Answer d: Smoke detectors--both photoelectric and ionization chamber
types--are regulated by the Consumer Product Safety Commission. The
radioactive source used in the ionization chamber detector is naturally
occurring, not electronic and, therefore, is not a substance that would
be regulated by FDA. (The level of radiation exposure to home occupants
from ionization chamber detectors is much less than that received from
the low level of natural background radiation.)

Under the FD&C Act, FDA is responsible for protecting consumers from
unnecessary exposure to radiation emitted from electronic products.
(These provisions were originally separate from the FD&C Act and were
referred to as the Radiation Control for Health and Safety Act. They
were later incorporated into the FD&C Act when the Safe Medical Devices
Act of 1990 was enacted). Airport security x-ray machines and microwave
ovens must be properly shielded so that the radiation generated by these
products (x-radiation and microwave radiation, respectively) does not
harm anyone. MRI diagnostic equipment is regulated as a medical device
under the FD&C Act. It is also subject to enforcement as an electronic
product emitting radiation because it uses radio waves and a strong
magnetic field to produce its images. Laser products used in lumber
mills must conform to an FDA standard that ensures their safety. This
standard applies to all laser products, whether medical, industrial or
consumer.

5. Answer c: The only advertisements over which FDA has direct
jurisdiction are those for prescription drugs. FTC oversees advertising
for other FDA-regulated products.

TV sets are regulated under the radiological health provisions of the
FD&C Act. All televisions must comply with a performance standard that
ensures their safety. This standard also applies to video display
terminals used with computers. Over-the-counter and prescription drugs,
as well as human biological products (such as vaccines and blood
products), are regulated by FDA. 

6. Answer a: Baby pacifiers are regulated by CPSC unless they are
marketed with health claims, in which case they are under FDA's
jurisdiction.

Food-contact articles, including baby bottle nipples, ceramic ware
intended for food use, and coffee mugs, are regulated by FDA. So are eye
charts, which, as diagnostic products, are considered to be medical
devices. 

7. Answer a: Illegal use of heroin is the responsibility of the Drug
Enforcement Administration, the key federal agency that polices illicit,
or "street," drugs. (If heroin were being studied for medical uses, FDA
would regulate it as an investigational drug.) 

Barbiturates are subject to abuse and thus may, potentially, wind up on
the "street," bringing them under DEA's purview. However, barbiturates
have legitimate medical uses, and FDA is responsible for ensuring they
are properly manufactured and labeled. FDA regulates methadone as a
drug, and methadone maintenance treatment programs are monitored under
regulations promulgated by both FDA and the National Institute on Drug
Abuse (NIDA). Medicinal oxygen is regulated by FDA as a drug. Animal
drugs, including veterinary tetracycline, are regulated by FDA. 

8. Answer e: Hair dryers are regulated by CPSC.

Kidney dialysis machines and tongue depressors, as different as they are
in complexity, are both considered to be medical devices. FDA regulates
non-fluoridated toothpastes as cosmetics, and fluoridated toothpastes as
drugs. 

9. Answer a: Labels on beer and other malt beverages, distilled spirits
(liquors), and wines are regulated by the Bureau of Alcohol, Tobacco,
and Firearms under the Federal Alcohol Administration Act.

Ground coffee, coffee beans, rabbit meat, and canned tuna are all
regulated by FDA as foods. (The Federal Meat Inspection Act, which gives
USDA authority over meat products, covers cattle, sheep, swine, goats,
and horses. Other meat products, including game meats such as rabbit,
are regulated by FDA.) 

10. Answer a: Home canning equipment, under a memorandum of
understanding between FDA and CPSC, is regulated by CPSC.

FDA's jurisdiction includes the facilities where the products it
regulates are stored, such as food and drug warehouses. Hearing aid
dispensing establishments are bound by specific FDA regulations that
impose conditions for the sale of hearing aids. The regulations attempt
to prevent misrepresentation and ensure adherence to proper medical
standards. Regarding exporting drugs, FDA continues to have authority
over its regulated products even when they are exported. 

11. Answer c: The FD&C Act specifically excludes soap from its
definition of cosmetics. CPSC regulates this product.

All of the other choices are defined as cosmetics and, therefore, are
regulated by FDA. 

12. Answer a: A vaccine for horses is a veterinary biological product.
FDA does not have jurisdiction over veterinary biologics. The Virus,
Serum, and Toxin Act gives this responsibility to USDA.

The FD&C Act gives FDA authority over pet foods and drugs, which would
include veterinary penicillin, medicated feeds, and bird feed. The
Public Health Service Act confers on FDA the authority to regulate the
interstate movement of psittacine birds (parrots, cockatoos, macaws,
parakeets, and other birds in the psittacine family). These birds are
potential carriers of psittacosis, a disease that can be transmitted to
people. Psittacosis, which is also known as parrot fever, can range in
severity from a mild respiratory infection to a protracted illness. 

13. Answer a: The safety of public drinking water (tap water) is
protected by EPA, as decided in an agreement between that agency and
FDA.

FDA has jurisdiction over bottled water, which is considered a food
under the FD&C Act. The remaining choices are also defined as foods. 

14. Answer b: Child-proof packaging authority, addressed under the
Poison Prevention Packaging Act, was delegated to CPSC.

Tamper-resistant packaging, which is required for certain OTC drugs,
cosmetics, and medical devices, is FDA's responsibility. Food packaging
materials, such as plastic containers and candy boxes, are subject to
regulation as food additives under the FD&C Act because of the
possibility that they may leach their chemical constituents into the
food product. These potential additives are referred to as indirect food
additives. A container bearing a drug product is considered to be a
component of that drug, and FDA, therefore, requires that it be
appropriate for that drug. 

15. Answer a: The animal counterpart of a cosmetic is commonly referred
to as a "grooming aid." Cosmetics, as defined in the FD&C Act, apply
only to human use. Therefore, products intended for cleansing or
promoting attractiveness of animals are not subject to FDA control.

An artificial limb for dogs is regulated as a veterinary medical device.
While such products do not require FDA approval, they do come under the
purview of the FD&C Act. They may not bear labeling that is false or
misleading, nor may they be otherwise misbranded or adulterated. The
laser scanner must comply with the standard. Mercury vapor lamps, most
often used to light streets, gymnasiums, sports arenas, banks, and
stores, must be maintained properly to be safe. With some types of
mercury vapor lamps, if the outer envelope is broken and the lamp
continues to operate, intense, harmful ultraviolet radiation is emitted.
An FDA standard ensures that this lighting is safe. Finally, FDA
regulates vitamin C tablets as food supplements.

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Updates



New Drug for Bone Disorders

Within six months of the manufacturer's submission of the application,
FDA approved a new drug to treat two bone disorders: osteoporosis in
postmenopausal women and Paget's disease.

Fosamax (alendronate) is the first bisphosphonate drug approved for
osteoporosis, providing an alternative to estrogen and calcitonin,
previously approved treatments. Fosamax was approved last Sept. 29.
Other bisphosphonates were previously approved for Paget's disease.

Osteoporosis is a condition of low bone mass and reduced bone strength
that leads to fractures of the spine, wrist and hip. In Paget's disease,
normal bone is replaced with poor quality bone.

In two three-year studies of more than 900 patients, bone strength
increased 8.16 percent in patients receiving alendronate and decreased
0.65 percent in those receiving a placebo. In addition to the drug
therapy, patients received a daily dietary calcium supplement. Adverse
effects associated with the drug include nausea, heartburn, flatulence,
and abdominal pain.

Fosamax should be used in conjunction with an adequate diet, including
enough vitamin D and calcium, and an exercise program. The drug should
be taken in the morning at least a half hour--preferably a full
hour--before eating or taking other medication.

The manufacturer is Merck and Co., of West Point, Pa. 

New Device to Treat Aneurysms

The first detachable coil for insertion through blood vessels of the
brain to treat inoperable or high-risk intracranial aneurysms was
recently cleared for marketing by FDA. The Guglielmi Detachable Coil
(GDC) is the first device of its type capable of being controlled during
placement in the aneurysm.

An intracranial aneurysm is a weak, balloon-like defect protruding from
an arterial wall on or inside the brain. The aneurysm can rupture,
causing hemorrhagic stroke, an event that results in death in more than
half the cases. Each year, about 10,000 patients are diagnosed with
inoperable or high-risk intracranial aneurysms.

Aneurysm rupture causes sudden severe headache, which may be combined
with nausea and vomiting. The patient may become unconscious. Intact
aneurysm may occur without symptoms, or may cause headache, dizziness,
visual problems, nausea, vomiting, and numbness.

The GDC is a soft platinum alloy micro-coil. Treatment usually requires
insertion of five to six coils.

In a controlled manner, the surgeon uses a micro-catheter to thread each
coil through blood vessels to the aneurysm site. Application of a
very-low-voltage electric current detaches and releases the coil into
the aneurysm. Once in place, the GDC coils fill the aneurysm, isolating
it from circulation to reduce the likelihood of rupture and hemorrhagic
stroke.

In clinical trials, only 3.7 percent of hemorrhagic stroke patients
treated with the GDC had a second such stroke during the following 7.3
months. Medical literature reports a 30 to 40 percent re-rupture rate in
patients with other treatment.

Among non-stroke patients treated with the GDC for very large aneurysms
causing symptoms, the death rate from all causes after 11 months was
12.8 percent. Medical literature reports a 62 percent death rate over
two years for such patients receiving other treatment.

Thirty percent of patients treated with the GDC had adverse events, many
of which were mild or moderate. More serious events included aneurysm
re-rupture, blood clot particles blocking blood vessels
(thromboembolism), and perforation of the aneurysm during placement of
the coils.

The GDC is manufactured by Target Therapeutics, Inc., of Fremont, Calif.
It was cleared for marketing last Sept. 8.

(For information about different types of aneurysms, see "Aneurysms
Difficult to Diagnose, Complex to Cure" in the October 1992 FDA
Consumer.) 

Medicare Extends Coverage To Some Investigational Devices

Under a new policy that became effective last Nov. 1, the Health Care
Financing Administration is extending Medicare coverage to pay for "new
generations" of medical devices while they are still under study for
marketing approval. Typically, these are new versions of proven
technologies already covered by Medicare. Reimbursement will be the same
as for comparable approved devices. 

Federal law prohibits Medicare from paying for "experimental" devices
still in clinical trials because safety and effectiveness have not been
established. Under HCFA's new policy, FDA will help the agency identify
"nonexperimental" devices eligible for the extended coverage. 

"All new devices need to undergo clinical trials, but most actually
represent refinements and improvements to existing devices," says FDA
Commissioner David A. Kessler, M.D. "This is an opportunity for teamwork
between HCFA and FDA to stimulate product development and make new
generations of technology available more quickly."

Medicare coverage for new generation devices will likely foster patient
enrollment in clinical trials and thus may encourage innovation. 

Treatment IND for Kidney Cancer Treatment

People suffering from advanced kidney cancer will have expanded access
to the first somatic cell therapy available under FDA's Treatment IND
(investigational new drug) regulations.

Somatic cell therapies use living cells, processed outside the source,
for the prevention, diagnosis or treatment of diseases or injuries. In
autolymphocyte therapy (ALT), the technology being investigated for
metastatic (stage IV) renal cell (kidney) cancer, white blood cells are
extracted from the patient, stimulated, and reintroduced into the
patient to help augment the immune system.

Treatment INDs allow patients suffering from serious or life-threatening
conditions who have exhausted established treatments or for whom no
satisfactory treatment exists to obtain promising experimental drugs
that have undergone sufficient clinical testing to show they may be safe
and effective.

FDA granted expanded access to ALT last September based on clinical data
that the activated somatic cells may decrease tumor size with few
serious side effects in a small percentage of patients.

The only approved treatment for metastatic kidney cancer is Proleukin
(interleukin-2). However, some patients cannot tolerate Proleukin's side
effects or do not respond favorably to the drug.

Under special permission from FDA, ALT's manufacturer, Cellcor Inc.,
Newton, Mass., is permitted to recoup costs for the treatment. Usually,
manufacturers cannot charge for a drug before it is approved. Patients
and health-care professionals can obtain more information about the
treatment and enrollment criteria by calling Cellcor at (1-800)
441-7901. 

Thalidomide Use in AIDS Treatment

Thalidomide would become more readily available to patients with AIDS
wasting syndrome under a revised research protocol being considered by
FDA, AIDS buyers' clubs, and a pharmaceutical company at press time in
November.

FDA had warned the buyers' clubs last September to stop selling the drug
to people not enrolled in approved studies. Most buyers' clubs then said
they planned to stop the practice in anticipation of the wider protocol
study. Some referred callers to FDA. Because of the health risks, FDA
believes the investigational drug should be used only in carefully
monitored clinical trials.

Thalidomide may cause adverse effects on the patient's nervous and
immune systems and is known to cause severe birth defects. Never
approved in the United States, the drug was sold in other parts of the
world in the 1950s and 1960s and became notorious for causing severe
fetal malformations when taken by pregnant women for nausea. The drug
was linked worldwide to the birth of an estimated 7,000 to 12,000 babies
without properly developed arms and legs.

FDA has authorized an expanded access protocol for thalidomide clinical
trials of HIV wasting syndrome so that substantially more people with
the syndrome may enroll in the studies. Information on the AIDS' studies
can be obtained by calling the AIDS Clinical Trials Information Service
at (1-800) TRIALS-A.

FDA believes thalidomide should be used only under medical supervision
and with informed consent, both of which are not usually available
outside of carefully monitored clinical trials. In addition, the illegal
distribution of thalidomide by buyers' clubs may hinder enrollment in
clinical trials, thereby delaying the determination of whether the drug
is safe or effective for treating certain conditions.

In clinical studies, thalidomide has been investigated for treating
erythema nodosum leprosum, a serious inflammatory condition in patients
with leprosy. The drug also is being investigated for aphthous ulcers,
painful HIV-related sores in the mouth and throat, and for AIDS-related
wasting syndrome.

FDA allows AIDS patients with aphthous ulcers who are not eligible for
larger thalidomide clinical trials treatment to get thalidomide through
their doctors by means of single-patient INDs (investigational new drug
applications). This allowance is based on early data showing the drug
may effectively treat the ulcers.

There already are two drugs approved for AIDS-related wasting: Marinol
(dronabinol) and Megace (megestrol acetate). (See "Warding Off HIV
Wasting Syndrome" in the April 1995 FDA Consumer.) In addition, FDA has
granted a Treatment IND for Serostim (somatotropin) to treat AIDS
wasting.

The buyers' clubs receiving the FDA warnings in September were LifeLink
of Arroyo Grande, Calif., Healing Alternatives of San Francisco, and PWA
Health Group of New York City. 

Fish on the Web

New information on seafood has been added to the agency's World Wide Web
site by FDA's Center for Food Safety and Applied Nutrition.

Featured are links to the FDA Seafood List and the Regulatory Fish
Encyclopedia, which was developed to help federal, state and local
officials and purchasers of seafood identify species substitution and
economic deception in the marketplace.

For 27 of the more frequently consumed fish, the encyclopedia includes:

 * color photos of the fish, both whole and as a fillet

 * information on its key physical measurements, geographic distribution,
and other available reference material

 * species biochemical pattern data in visual and text formats.

Selected chapters from the center's handbook "Foodborne Pathogenic
Microorganisms and Natural Toxins" (also known as "The Bad Bug Book")
are online, with hypertext links to relevant documents from the national
Centers for Disease Control and Prevention and U.S. Department of
Agriculture.

Also included is information on the FDA Seafood Hotline, the agency's
pesticide monitoring program, and links to the FDA Import System, which
includes access to FDA import alerts.

To locate the new information, go to http://vm.cfsan.fda.gov/list.html
and select "Seafood" (which is flagged with a red "new" icon). 

Plan to Reduce Vibrio Infections

The Interstate Shellfish Sanitation Conference (ISSC)--made up of
representatives from FDA and other federal and state regulatory
agencies, industry, and academia--has developed a plan to reduce risk of
infection from Vibrio vulnificus, a potentially harmful bacterium found
in raw or partially cooked oysters.

The plan is an interim measure while officials explore other ways to
curb the bacterial infection.

Vibrio vulnificus can be life-threatening to people with serious
underlying health problems such as liver disease, diabetes, cancer, or
immune disorders. Such people should not eat any raw or partially cooked
animal protein products, including oysters. Because some of these health
problems have no symptoms, individuals may not know they are at risk.
Those uncertain should check with their doctors.

The ISSC plan calls for states whose waters have been confirmed as the
original source of oysters associated with two or more Vibrio vulnificus
illnesses to require that oysters be refrigerated within a specified
time after harvest to slow the bacterium's growth. The higher the water
temperature, the sooner the oysters would have to be refrigerated.

For example, oysters taken from an affected site during a month with an
average monthly maximum water temperature of more than 84 degrees
Fahrenheit (29 degrees Celsius) would have to be chilled within six
hours of harvesting. Oysters from cooler waters could be kept unchilled
correspondingly longer. The times between harvest and cooling result
from FDA research on how rapidly Vibrio vulnificus multiplies in
unrefrigerated oysters after harvest.

For more information on oysters and related subjects, call the FDA
Seafood Hotline, (1-800) FDA-4010. Information is also available on the
agency's World Wide Web site (see "Fish on the Web" in this section). 

FDA Issues Warning About Hospital Bed Side Rails

Hospital bed side rails pose a risk of trapping certain patients during
use, FDA warned in a recent safety alert to health-care workers.

Since January 1990, FDA has received 102 reports of head and body
entrapments involving hospital bed side rails. The 68 deaths, 22
injuries, and 12 entrapments without injury occurred in hospitals,
long-term care facilities, and private homes. Although the number of
reported incidents is small compared to the large number of patients who
use hospital beds--well over a million, according to some
estimates--appropriate precautions can further reduce accidents, the
Aug. 23, 1995, alert stated.

All reported entrapments occurred in one of the following ways:

 * through the bars of an individual side rail

 * through the space between split side rails

 * between the side rail and mattress

 * between the headboard or footboard, side rail, and mattress.

All deaths involved entrapment of the head, neck or chest, while most
injuries involved fractures, cuts and abrasions to the arms and legs.
The majority of deaths and injuries involved elderly patients. Patients
at high risk include those who are mentally unstable, restless, lack
muscle control, or a combination of these factors. Risk also increases
if the bed dimensions are inappropriate for the patient's size and body
weight.

FDA recommends the following to people caring for patients in hospital
beds:

 * Inspect all hospital bed frames, side rails, and mattresses as part
   of a regular maintenance program to identify areas of possible
   entrapment.

 * Be alert to replacement mattresses and side rails whose dimensions
   differ from those of the original equipment or the bed frame
   manufacturer's specifications.

 * Check bed side rails for proper installation using the manufacturer's
   instructions to ensure a proper fit.

 * Consider additional safety measures for patients at high risk for
   entrapment.

 * Do not use bed side rails as a substitute for patient protective
   restraints.

Injuries from hospital bed side rails should be reported to FDA's
Medical Product Reporting Program, MedWatch (HF-2), Rockville, MD 20857;
telephone (1-800) FDA-1088; or computer modem (1-800) FDA-7737. 

Free Lupus Education Kit

A free education kit on lupus can help local organizers alert young
black women to signs of this serious immune disorder.

Affecting as many as 1 in 250 black women, lupus has an incidence,
prevalence and death rate three times higher in black women than in
white women. (See also "Living with Lupus" in the December 1989-January
1990 FDA Consumer.)

"What Black Women Should Know About Lupus: Ideas for Community Programs"
is available from the National Institute of Arthritis and
Musculoskeletal and Skin Diseases. To order a free copy, write: Lupus
Kit, NAMSIC, National Institutes of Health, 1 AMS Circle, Bethesda, MD
20892-3675; telephone (301) 495-4484; TDD (301) 565-2966.


------------------------------------------------------------------------


Notebook


The Notebook: a potpourri of items of interest gathered from FDA news
releases, other news sources, and the Federal Register (designated FR,
with date of publication). The Federal Register is available in many
public libraries.



Radiation-emitting electronic devices are now regulated by new and
revised record-keeping and adverse event reporting requirements,
according to an FDA final rule that took effect last Oct. 19. The rule
is intended to improve public health protection while reducing
regulatory burdens on manufacturers, dealers and distributors. (FR Sept.
19)

Food label information for restaurants is now available from FDA. "Food
Labeling, Questions and Answers, Volume II: A Guide for Restaurants and
Other Retail Establishments" answers some of the most frequently asked
questions about implementation of the Nutrition Labeling and Education
Act of 1990. Copies are available from the Superintendent of Documents,
U.S. Government Printing Office, Washington, DC 20402. Request order
number 017-012-00374-5. (FR Sept. 19)

Dogs with heartworm disease now have another treatment. Last July 21,
FDA approved Immiticide Sterile Powder (melarsomine dihydrochloride)
injection for treating heartworm disease. The manufacturer is Rhone
Merieux, Inc., of Overland Park, Kan. (FR Sept. 25)

Clindamycin phosphate vaginal cream's new antibiotic drug standards were
accepted by FDA, according to a final rule that took effect Oct. 26. The
rule sets standards of identity, strength, quality, and purity for the
drug product. (FR Sept. 26)

Irradiation of poultry feeds and ingredients is now permitted, according
to an FDA final rule effective last Sept. 28. The rule allows use of
gamma radiation from cobalt-60 in the production, processing and
handling of poultry feed to eliminate Salmonella. (FR Sept. 28)

Food stamps can now be received by certain college students under a U.S.
Department of Agriculture final rule effective last Nov. 1. Eligible are
single parents caring for a child under 12 while attending full-time
classes and students attending college at least part-time if they are:
between 50 and 60 years old; responsible for a child between 5 and 12
and unable to afford adequate child care that would permit attending
class and working a minimum of 20 hours a week; participating in a
state-financed work-study program; enrolled in the Job Opportunities and
Basic Skills Program; assigned to a college by the food stamp employment
and training program. (FR Sept. 21)

Aquatic life toxicity information on the chemical di(2-ethylhexyl)
phthalate (DEHP) is available from the Environmental Protection Agency.
Used in making many types of plastics, DEHP can damage aquatic life. For
free copies of the information, write to EPA, National Center for
Environmental Publications and Information, 11029 Kenwood Road,
Cincinnati, OH 45242; telephone (513) 489-8190; E-mail
waterpubs@epamail.epa.gov. (FR Sept. 26) 

------------------------------------------------------------------------



Investigators' Reports



Prizes Forfeited for Illegally Drugged Show Animals

by Marian Segal

A recent FDA investigation was instrumental in the enactment of a new
law in Colorado making it a crime in that state for livestock exhibitors
to give show animals illegal growth drugs. Violators are subject to a
maximum punishment of 18 months in prison and a $100,000 fine.

Colorado Governor Roy Romer signed the law in May 1995, following events
surrounding results of a competition at the Denver National Western
Junior Livestock Show the preceding January. Both first- and
second-place winners in the Junior Steers Class tested positive for
clenbuterol, an illegal animal drug that promotes muscle growth. 

Clenbuterol is approved in Canada and some European and South American
countries to treat respiratory problems in horses, but no country has
approved its use in food-producing animals. It is not approved for any
use in the United States.

Agency surveillance at livestock shows over the last several years has
found the drug continues to be used in animals entered for competition.
These animals have often been slaughtered for food, with their meat
ending up on dinner plates.

In 1990, 135 people in Spain became ill from eating beef liver that
contained clenbuterol residues. The victims had symptoms that included
fast heart rate, muscle tremors, headache, dizziness, nausea, fever, and
chills. Later, there were reports of 22 illnesses in eight families in
France.

The Denver investigation began when FDA Dallas district compliance
officer Reynaldo Rodriguez called the agency's Denver office with a tip
that some animals at the National Western Show might have been given
clenbuterol.

On Jan. 25, 1995, FDA investigator Donald Bean collected eyeballs from
the first- and second-place winners--Grand Champion and Reserve Grand
Champion--in the classes Junior Steers, Swine, and Sheep. Testing by the
agency's Denver laboratory showed the eyes from the steers contained
clenbuterol. Denver sent the samples to the agency's Cincinnati Forensic
Laboratory for confirmatory testing, which was obtained on Feb. 9.

FDA informed National Western officials that the two animals tested
positive for clenbuterol, and they in turn informed the exhibitors and
their parents.

"The kids that show animals in the junior livestock competitions are
usually in FFA or 4-H," says John Vodneck, a compliance officer with
FDA's Denver district. "A tremendous amount of money can be paid for
these animals. At this show [the Denver National Western], the Grand
Champion was sold at auction for $37,500 and the Reserve Champion for
$12,000. In some shows it can go up to $150,000. The auctions are
intended to be a way for rural youngsters to win money for college," he
says.

National Western appointed a special committee to investigate the
illegal use of clenbuterol in the winning steers. The committee began
hearings in early March. On March 9, Bean testified about his sample
collection, and other FDA officials described how the samples were
screened and tested. Other experts provided information about
clenbuterol (such as how long it stays in various organs) and about the
validity of FDA's test method.

Following the testimony, the committee passed a resolution recommending
that the purchase price of the animals be returned to the buyers.

"The hearing was to continue on March 15 and 16, but before it resumed,
the exhibitors entered into an agreement with National Western," says
Vodneck. "None of the exhibitors or their attorneys showed up for the
hearings." 

In a public statement and apology, the exhibitors said, "Although we
initially disputed the accuracy of the [FDA] tests, we now acknowledge
that the tests were accurate and that residues of clenbuterol were
present in both steers. As the owners and exhibitors of those steers, we
must take full responsibility for the presence of the drug in the
steers."

In their agreement with National Western, the exhibitors stipulated the
following:

 * The Grand Champion steer and Reserve Grand Champion steer are
   disqualified.

 * The exhibitors of the Grand Champion and the Reserve Grand Champion are
   disqualified.

 * The exhibitors of the two steers are to return all prizes, awards and
   ribbons.

 * The exhibitors agree to return all money paid by the purchasers of the steers.

 * The exhibitors are barred from exhibiting any animal at any future National Western Stock Show.

Because of the continuing use of clenbuterol in show animals, future
winners at the National Western will be slaughtered immediately for drug
testing instead of being put on display.

Also, Vodneck says, some meat packers have written to show officials
saying they will stop buying show animals unless reliable safeguards
against drugs are instituted. One packer has a laboratory that screens
for the drug.

Marian Segal is a member of FDA's public affairs staff.


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Diet Nutrition Bars Seized, Destroyed

Like any other food, chocolate bars, whether sold as candy or as part of
a weight-loss program, must contain the vitamins and minerals claimed on
the label.

More than 36,000 chocolate Ultra Diet Nutrition Bars, valued at more
than $9,000, were destroyed last April 13 after FDA analysis found the
bars contained significantly less riboflavin and vitamin C than the
labels claimed.

FDA's Chicago district conducted a routine inspection March 2, 1994, of
Dietary Enterprises, Ltd., also known as The Diet Store of Morton Grove,
Ill., a distributor of weight-loss products. Agency investigators
collected several samples of the Ultra Diet Nutrition Bars sold through
Dietary Enterprises and sent them to FDA's Atlanta Center for
Nutritional Analysis.

Laboratory analysis found that the bars, which were labeled as
containing 33 percent of the U.S. Recommended Daily Allowance (RDA) for
riboflavin, only contained 5.25 percent of the RDA. The label also
stated that the bars contained 30 percent of the RDA of vitamin C, but
they actually contained only from 1.2 to 2.45 percent of the RDA. In
addition, the labels contained incorrect information--The Diet Store was
listed as the product's distributor when, in fact, that firm does not
appear in any local telephone directory.

On Aug. 4, when FDA investigators returned to Dietary Enterprises, they
found that all the adulterated and misbranded products had been sold.
FDA considered the products adulterated and misbranded because the bars
contained significantly less riboflavin and vitamin C than were listed
on the label, the product's labeling was false and misleading, and the
nutrition information, ingredients statement, and name and place of
business of the distributor were not prominently placed on the label.

Investigators again inspected the firm on Aug. 23, and again collected
Ultra Diet Nutrition Bar samples. Laboratory analysis again found the
products lacking significant amounts of riboflavin and vitamin C. At
FDA's request, Illinois embargoed the lot.

On Nov. 3, 1994, also at the agency's request, the U.S. District Court
for the Northern District of Illinois Eastern Division ordered a U.S.
marshal to seize 601 cases of Ultra Diet Nutrition Bars stored in
Dietary Enterprises' offices.

When Dietary Enterprises failed to claim the bars, the U.S. attorney
entered a default decree of condemnation on Dec. 28, 1994, and on April
13, 1995, the products were destroyed in a local landfill.

--Kevin L. Ropp


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Smuggled Frog Legs Destroyed

The three import shipments were labeled as shrimp from Bangladesh. When
U.S. Customs Service agents examined individual cartons, however, they
found the three middle layers of cartons contained not shrimp, but frog
legs--later identified as being from the endangered species Rana
tigerina.

Endangered species are protected under the Convention on International
Trade in Endangered Species (CITES), a treaty signed by most countries,
including the United States and Bangladesh.

Investigation by FDA, Customs, and the U.S. Fish and Wildlife Service
revealed that Flag Imports, Inc., of Secaucus, N.J., altered labeling
and invoices to defraud the government, never obtained permission from
Bangladesh to export the protected frog legs, and often imported seafood
contaminated with Salmonella bacteria. Following seizure of the
shipments in 1993, U.S. District Judge John Lifland in Newark, N.J., on
June 30, 1995, ordered the products condemned and forfeited for
destruction.

Customs and FDA had been keeping a wary eye on Flag Imports since 1990,
when routine examination of sampling worksheets by FDA investigator John
Moore of the agency's New York district office revealed the firm was
falsifying invoices.

The investigation, in fact, led to a 138-count conviction in 1993 of
Flag's president, Thekkedajh Menon. (See "Importer Sentenced in Tainted
Seafood Case," in the September 1993 FDA Consumer.) Menon appealed,
arguing that the convictions were based on a law that required proof of
intent to deprive the United States of revenue, and that this had not
been proven. Agreeing with Menon, an appeals court reversed all but one
conviction. The court upheld Menon's conviction for fraudulently
re-importing contaminated shrimp previously rejected by FDA.

Flag's first two shipments of shrimp and concealed frog legs arrived at
Port Elizabeth, N.J., on May 30, 1992. Invoices and labeling identified
the contents as Sony Brand black tiger shrimp from Sundarban Sea Food
Industries, Ltd., Bangladesh. A third shipment arrived at Oakland,
Calif., on June 6, and was sent on to Port Newark, N.J., where it
arrived June 15.

Also, on June 6, Customs notified FDA that a routine examination of the
Port Elizabeth shipments found frog legs concealed in the middle
cartons. FDA automatically detains imported frog legs for Salmonella
testing.

In addition, Bangladesh bans exportation of Rana tigerina frog legs for
ecological reasons. A firm wanting to export them would need a CITES
certificate from that country, authorizing their export. Flag did not
have CITES certificates for any of its shipments.

On July 2, the Fish and Wildlife Service seized the shipments under its
administrative authority, and moved them to a South Plainfield, N.J.,
warehouse. A Fish and Wildlife Service forensic herpetologist (expert on
reptiles and amphibians) identified the frog legs as Rana tigerina.

FDA sampled the shipments, and agency testing revealed Salmonella in
both the frog legs and the shrimp. 

On Jan. 13, 1993, a complaint for seizure, condemnation and forfeiture
of the goods was filed in federal court under the Endangered Species Act
(ESA), the Lacey Act, and the Federal Food, Drug, and Cosmetic (FD&C)
Act, and U.S. marshals seized the shipments.

On May 31, 1994, in cooperation with FDA and the Fish and Wildlife
Service, the U.S. Attorney's Office in Newark sought a summary judgment
of condemnation, forfeiture and destruction of the three shipments of
shrimp and frog legs.

Judge Lifland ruled that the shipments violated the ESA because Flag had
no CITES certificates to authorize exporting the protected frog legs.
Because the shrimp was used to conceal the illegally imported frog legs,
Lifland ruled it forfeited under the ESA as well.

Lifland found that the government had probable cause to believe the
three shipments violated the Lacey Act Amendments' prohibition against
false labeling of imported fish and wildlife.

Flag argued that under Section 801(a) of the FD&C Act, it had the right
to export, rather than forfeit, the shipments. Lifland ruled that even
if the section might confer this right, "such a right would not prevail
in the face of condemnation and forfeiture under the ESA and the Lacey
Act."

Furthermore, Lifland stated that even if Section 801(a) applied, FDA
would still be justified under the FD&C Act in requesting seizure,
condemnation and forfeiture of the products because of the circumstances
of the case.

"Shrimp was used," he wrote, "in what can only be described as a
deliberate attempt to conceal Rana tigerina frog legs. It does not seem
too cynical a position to hold that the FDA would be reasonable in
believing on this basis that re-import of the res [the seized shipments]
was likely." He added, "The history of Flag Imports gives credence to
this conclusion."

Lifland condemned the shipments and ordered them forfeited for
destruction. He also ordered that the government is entitled under the
FD&C Act to costs, fees, and storage and other proper expenses.

--Dixie Farley


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Drug Thefts at VA Hospital Lead to Jail Term

A pharmacy technician at the Veterans Affairs Medical Center in
Brooklyn, N.Y., is serving a year in jail for stealing more than $60,000
worth of prescription drugs from the VA hospital and selling them to
local retail pharmacies. 

Bruce Weiss, 35, of Staten Island, N.Y., was sentenced March 28, 1995,
in U.S. District Court, Eastern District of New York, to 12 months in
prison and three years of supervised release. He was also fined $50 and
ordered to pay $60,000 restitution. Weiss began his jail sentence in
June. 

On Aug. 24, 1993, an agent from the Department of Veterans Affairs'
Office of the Inspector General (VA OIG) contacted FDA's Office of
Criminal Investigations (OCI) in New York to enlist cooperation in an
investigation of drug thefts from the Brooklyn VA Medical Center. The VA
had been tipped off to Weiss' activities by an informant. At the same
time, the medical center notified the Federal Bureau of Investigation,
and the three agencies subsequently conducted a joint investigation of
the thefts.

According to OCI, an eight-week FBI surveillance of Weiss, beginning in
October 1993, revealed that Weiss often carried "things" under his
jacket as he walked out of the hospital during lunch hour and after
work. He would glance furtively to the left and right, open the car
trunk, and throw things into it or the back seat. A couple times after
driving away, he would turn a corner two or three times, circling as
though checking to see if he was being followed.

Surveillance photos also showed Weiss going into pharmacies carrying
things under his jacket and leaving empty-handed. According to the
investigating agents, this evidence--although circumstantial--was highly
suspicious. 

At around this same time, the VA OIG conducted audits of the hospital
and found approximately $500,000 worth of drugs missing due to thefts,
pilferage or waste.

In February 1994, agents from the VA OIG, the FBI, and FDA OCI decided
to approach one of the pharmacists Weiss visited. The pharmacist
admitted that he dealt with Weiss, that he knew Weiss was a government
employee, and that Weiss brought him drugs that were stolen from the VA.
He said he bought the drugs from Weiss, paying half the average
wholesale price. The drugs were valued at $50,000 to $60,000. He said he
met with Weiss approximately 25 to 35 times from January 1992 to March
1994, when he purchased the stolen drugs.

The pharmacist surrendered to the agents drugs he had purchased from
Weiss. They were the same kinds of drugs as those in the VA's inventory. 

Meanwhile, OCI and VA OIG agents interviewed VA employees and local
retail pharmacies. They talked with other pharmacy technicians Weiss
socialized with and worked with in the supply areas. All those
interviewed denied participating in any of Weiss' activities or seeing
anything illegal.

Early in June 1994, agents from OCI, VA OIG, and the FBI went to see
Weiss at his residence. They told him they were conducting a
three-agency investigation into thefts at VA pharmacies and that they
would like to speak to him about his activities. 

At the request of the agents, Weiss went to the FBI office to be
interviewed. The agents hoped he would cooperate with their
investigation, but he refused. Weiss admitted to stealing for personal
use small quantities of creams and lotions, which he valued at about
$30,000. However, during another interview at the U.S. attorney's
office, with his attorney present, Weiss admitted to stealing drugs
worth $65,000. Every time Weiss was interviewed, he upped the value of
the stolen drugs. 

On June 14, 1994, the Department of Justice filed a criminal complaint
charging Weiss with theft of government property, and on June 21, he was
arrested. He was indicted by a federal grand jury on Aug. 19. 

On Oct. 28, Weiss pleaded guilty and was to be sentenced, yet he
challenged the $60,000 estimated value of the items he was charged with
stealing. Also, his attorney maintained that Weiss had cooperated fully
with the investigation and appealed to the judge to consider this in
sentencing.

The prosecution, however, pointed out that Weiss continually set
conditions on his cooperation, and that the government considered the
$60,000 estimate to be very conservative, since it was based on only one
of the five pharmacies Weiss admitted to dealing with.

The judge sentenced Weiss to 12 months in jail. 

There have been no reports of theft at the Brooklyn VA Medical Center
since the Weiss investigation.

--Marian Segal 


------------------------------------------------------------------------

Summaries of Court Actions



Summaries of Court Actions are given pursuant to Section 705 of the
Federal Food, Drug, and Cosmetic Act. Summaries of Court Actions report
cases involving seizure proceedings, criminal proceedings, and
injunction proceedings. Seizure proceedings are civil actions taken
against goods alleged to be in violation, and criminal and injunction
proceedings are against firms or individuals charged to be responsible
for violations. The cases generally involve foods, drugs, devices, or
cosmetics alleged to be adulterated or misbranded or otherwise violative
of the law when introduced into and while in interstate commerce.

Summaries of Court Actions are prepared by Food and Drug Division,
Office of the General Counsel, HHS, and are published by direction of
the Secretary of Health and Human Services.



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SEIZURE ACTIONS



Food/Contamination, Spoilage, Insanitary Handling

PRODUCT: California Shelled Almonds, at Forest View, Ill. (E.D.Ill.);
Civil No. 94C-6155.

CHARGED 10-11-94: While held for sale after shipment in interstate
commerce at Freight-A-Ranger, Inc., in Forest View, Ill., the articles
were adulterated in that they contained insect-damaged nuts--402(a)(3).

DISPOSITION: A consent decree of condemnation and forfeiture was
entered. The articles were reconditioned. (F.D.C. No. 67025; S. No.
94-741-151; S.J. No. 1)


PRODUCT: Chunk Light Tuna, at San Diego, Calif. (S.D.Calif.); Civil No.
94-97OH(BTM).

CHARGED 6-30-94: While held for sale after shipment in interstate
commerce at Van Camp Seafood Company, Inc., in San Diego, Calif., the
article was adulterated in that it contained decomposed tuna--402(a)(3).

DISPOSITION: A default decree of condemnation, forfeiture and
destruction ordered the article destroyed. (F.D.C. No. 66939; S. No.
64-624-545; S.J. No. 2)


PRODUCT: Dried Shark Fins, at San Francisco, Calif. (N.D.Calif.); Civil
No. C94-3109.

CHARGED 9-1-94: While held for sale after shipment in interstate
commerce at Four Seas Enterprises, Inc., in San Francisco, Calif., the
articles were adulterated in that they contained live and dead adult and
larval insects, and insect filth. The articles were also held under
insanitary conditions whereby they might have been contaminated with
filth--402(a)(3) and 402(a)(4).

DISPOSITION: A consent decree of condemnation ordered the articles
destroyed. (F.D.C. No. 67012; S. No. 94-665-457; S.J. No. 3)


PRODUCT: Mushrooms, slices, at Philadelphia, Pa. (E.D.Pa.); Civil No.
95-483.

CHARGED 1-27-95: While held for sale after shipment in interstate
commerce at Asia Foods in Philadelphia, Pa., the articles were
adulterated in that they contained an added poisonous and deleterious
substance, and they were prepared and packed under conditions which
might have rendered them injurious to health--402(a)(1) and 402(a)(4).
The articles were misbranded in that their labeling falsely represented
that the articles were packed in Hong Kong--403(a)(1).

DISPOSITION: A default decree of condemnation, forfeiture and
destruction ordered the articles destroyed. (F.D.C. No. 67056; S. No.
95-786-249; S.J. No. 4)



PRODUCT: Natural Brown Rice, at Brooklyn, N.Y. (E.D.N.Y.); Civil No.
CV-95-0360.

CHARGED 1-25-95: While held for sale after shipment in interstate
commerce at Foodland Industries, Inc., in Brooklyn, N.Y., the article
was adulterated in that it contained rodent excreta and rodent hair, and
the articles were held under insanitary conditions--402(a)(3) and
402(a)(4). 

DISPOSITION: A decree of forfeiture and order of final delivery ordered
the articles destroyed. (F.D.C. No. 67047; S. No. 94-725-039; S.J. No.
5)


PRODUCT: Rock Lobster Tails, at Secaucus, N.J. (D.N.J.); Civil No.
90-876.

CHARGED 3-7-90: While held for sale after shipment in interstate
commerce at Far Port International, Inc., in Secaucus, N.J., the
articles were adulterated in that they consisted of decomposed lobster
tails--402(a)(3). The articles were misbranded in that their labels
failed to bear the presence of a chemical preservative--403(k).

DISPOSITION: An order for entry of default, default judgment, and decree
of condemnation and destruction ordered the articles destroyed. (F.D.C.
No. 65813; S. No. 876665; S.J. No. 6)


PRODUCT: Shrimp, frozen, at Los Angeles, Calif. (C.D.Calif.); Civil No.
95-2335 WDK.

CHARGED 4-11-95: While held for sale after shipment in interstate
commerce at U.S. Growers Cold Storage, Inc., in Los Angeles, Calif., the
article was adulterated in that it contained decomposed
shrimp--402(a)(3).

DISPOSITION: A default judgment ordered the articles destroyed. (F.D.C.
No. 67066; S. No. 95-683-913; S.J. No. 7)


PRODUCT: Ultra Rich and Slim Nutrition Bars, at Niles, Ill. (N.D.Ill.);
Civil No. 94C-6593.

CHARGED 11-3-94: While held for sale after shipment of one or more of
its ingredients in interstate commerce at Dietary Enterprises, Ltd.,
d/b/a The Diet Store, Ltd., in Niles, Ill., the articles were
adulterated in that vitamin C and riboflavin were omitted from the
food--402(b)(1). The articles were misbranded in that their labeling
falsely represented that the articles provided 30 percent of the U.S.
Recommended Daily Allowance (RDA) of vitamin C and 33 percent of the
U.S. RDA of riboflavin when, in fact, they provided from 4.07 to 8.2
percent of the U.S. RDA of vitamin C and from 16 to 16.6 percent of the
U.S. RDA of riboflavin per serving--403(a)(1). The articles were also
misbranded in that the nutrition information, the ingredients statement,
and the name and place of business of the distributor were not
prominently placed on the label. Furthermore, the label statement of the
net quantity of contents on the package did not contain letters or
numerals in the established type size --403(f).

DISPOSITION: A default decree of condemnation ordered the articles
destroyed. (F.D.C. No. 67005; S. No. 94-711-111; S.J. No. 8)



Drugs/Human Use

PRODUCT: Isocom, capsules, at Downey, Calif. (C.D.Calif.); Civil No.
95-0912-TJH.

CHARGED 2-13-95: While held for sale after shipment of one or more of
its components in interstate commerce at Kaiser Foundation Hospital in
Downey, Calif., the articles were adulterated in that the methods used
in, and the facilities and controls used for, its manufacture,
processing, packing, and holding did not conform to and were not
operated and administered in conformity with current good manufacturing
practice requirements--501(a)(2)(B).

DISPOSITION: A default judgment ordered the articles destroyed. (F.D.C.
67055; S. No. 94-707-518; S.J. No. 9)



Medical Devices

PRODUCT: Spot Ion Clinica, High Genki Spot Vibrator, and High Genki
Junior, at Honolulu, Hawaii (D.Hawaii); Civil No. 93-00862.

CHARGED 11-9-93: While held for sale after shipment in interstate
commerce at Japan International Karate Center, d/b/a International Ki
Institute for Health Management and Research, in Honolulu, Hawaii, the
articles were adulterated in that they were class III devices without an
application for premarket approval--501(f)(1)(B). The articles were
misbranded in that they failed to bear adequate directions for use, and
notices regarding the articles were not provided to FDA prior to their
introduction into interstate commerce--502(f)(1) and 502(o).

DISPOSITION: A default judgment and decree of forfeiture was entered,
and the articles were used as agency exhibits. (F.D.C. No. 66780; S. No.
93-706-061; S.J. No. 10)


------------------------------------------------------------------------


CRIMINAL ACTIONS

DEFENDANT: Gary Allen, at Dallas, Texas (N.D.Texas); Criminal No.
3:94-CR-102-R.

CHARGED 3-24-94: Count 1: The defendant knowingly made a false statement
during an inspection where he told FDA agents that he had not received
any products containing gamma hydroxybutyric acid (GHB) from any other
supplier when, in fact, he had received GHB products from at least one
other source--18 U.S.C. section 1001. Count 2: The defendant, with the
intent to defraud and mislead, caused 50 misbranded bottles of GHB to be
introduced in interstate commerce. The bottles were misbranded in that
they were in package form and did not bear labels containing the name
and place of business of the manufacturer, packer and distributor or an
accurate statement of the quantity of the contents in terms of weight
measure and numerical count--502(b). The bottles were also misbranded in
that the labels failed to bear the established name of the drug and
adequate directions for use--301(a), 303(a)(2), and 18 U.S.C. section 2.

DISPOSITION: Guilty plea; sentenced to 33 months in prison and three
years of supervised release. (F.D.C. No. 66859; S.J. No. 11)


DEFENDANT: Jeffrey Michael Dyer, d/b/a Champion Distributors, at
Horsham, Pa. (E.D.Pa.); Criminal No. 92-0009-01.

CHARGED 6-6-91: Count 1: The defendant caused to be introduced into
interstate commerce a bulk quantity of GHB which was misbranded in that
the labels failed to bear adequate directions for use--301(a),
303(a)(1), and 18 U.S.C. section 2. Count 2: The defendant caused the
introduction of an unapproved new drug into interstate commerce--301(d)
and 303(a)(1).

DISPOSITION: Guilty plea; sentenced to 18 months' probation and fined
$500. (F.D.C. No. 66107; S.J. No. 12)



DEFENDANTS: Peninsular Products Company, Flavor Fresh Foods Corp.,
Edward B. Crouse, William B. Laviolette, George R. Reynolds, Saad Alhir,
James R. Marshall, James E. Benton, and Friedrich R. Kohlbach, at
Lansing, Mich. (W.D.Mich.); Criminal No. 1:93-CR-21.

CHARGED 2-18-83: Count 1: The defendants knowingly caused, with the
intent to defraud and mislead, one or more of the components of
adulterated and misbranded orange juice from concentrate and
concentrated orange juice for manufacturing to be introduced into
interstate commerce--301(a), 301(k), and 303(b). The defendants violated
the Federal Mail Fraud and Wire Fraud Statutes by devising a scheme to
obtain money and property from buyers of orange juice from concentrate
and concentrated orange juice for manufacturing under false
pretenses--18 U.S.C. sections 1341 and 1343. 

Counts 2-9: The defendants knowingly devised a scheme to obtain money
and property from buyers of orange juice from concentrate and
concentrated orange juice for manufacturing under false pretenses--18
U.S.C. section 1341. In an attempt to execute the scheme, the defendants
mailed false and fraudulent invoices to the buyers--18 U.S.C. section 2. 

Counts 10-15: In an attempt to execute a scheme to defraud customers of
products represented to be orange juice from concentrate and
concentrated orange juice for manufacturing, the defendants transmitted
facsimiles of letters in interstate and foreign commerce--18 U.S.C.
sections 2 and 1341. 

Counts 16-22: The defendants caused foods to be adulterated in that beet
sugar and syrup were substituted in part for orange juice and orange
juice concentrate. Citric and amino acids were added to those foods to
conceal damage and inferiority--402(b)(2) and 402(b)(3). Defendants also
caused foods to be adulterated in that citric and amino acids and
preservatives were added to and mixed and packed with those foods to
make them appear of greater value--402(b)(4). 

Counts 23-30: The defendants caused foods to be misbranded in that the
labeling falsely represented that the foods consisted only of orange
juice from concentrate when they contained large amounts of beet sugar
and syrup, preservatives, and citric and amino acids--403(a)(1). The
defendants also caused orange juice from concentrate to be misbranded in
that it was composed of ingredients not permitted by the definition and
standard of identity as prescribed by the regulations--403(g). 

Count 31: The defendant caused the food represented as 100 percent pure
orange juice from concentrate to be adulterated in that orange pulpwash
was substituted for orange juice and orange juice from concentrate, and
a preservative was added to and mixed and packed with the food to make
it appear of greater value--402(b)(2) and 402(b)(4). 

Count 32: The defendants caused food to be misbranded in that the
labeling falsely represented the food as containing 100 percent pure
orange juice from concentrate when it also contained orange pulpwash and
preservatives--403(a)(1). The defendants also caused the food to be
misbranded in that orange juice from concentrate was composed of
ingredients not permitted by the definition and standard of identity as
prescribed by the regulations--403(g). 

Count 33: Defendant Edward B. Crouse, while testifying in a grand jury
proceeding, made a false material statement regarding his knowledge of
the addition of adulterants such as pulpwash, sugars, antibiotics, and
preservatives to products manufactured by Peninsular--18 U.S.C. section
1623.

DISPOSITION: The charges against Peninsular Products were dropped
because the company went bankrupt. Flavor Fresh Corp. pleaded guilty to
counts 1-32 and was fined $320,000. James Marshal pleaded guilty to
counts 1-15. He was sentenced to 37 months in prison and fined $125,000.
James Benton pleaded guilty to count 15. He was sentenced to 30 months
in prison and fined $25,000. Saad Alhir pleaded guilty to count 31. He
was sentenced to one month in prison, five months of home confinement,
and six months of probation. Friedrich Kohlbach was sentenced to two
years' probation and fined $100,000. Donald Wagoner pleaded guilty to
count one. He was sentenced to one year's probation and fined $1,000.
Edward Crouse pleaded guilty to count 15. He was sentenced to 18 months
in prison, 12 months of home confinement, and 12 months of probation.
William Laviolette pleaded guilty to count one. He was sentenced to one
year's probation and fined $5,000. George Reynolds pleaded guilty to
count one. He wa s sentenced to one year's probation and fined $5,000.
(F.D.C. No. 66106; S. No. 91-554-168; S.J. No. 13)


------------------------------------------------------------------------


INJUNCTION ACTIONS

DEFENDANT: Ricardo Samitier, M.D., d/b/a A New You, The Institute of
Cosmetic Surgery, Inc., at Miami, Fla. (S.D.Fla.); Civil No. 93-0518.

CHARGED 3-16-93: The defendant ordered liquid injectable silicone, an
unapproved medical device, from sources outside of Florida and caused
the introduction of an adulterated medical device into interstate
commerce--301(a). While held for sale after interstate shipment at A New
You in North Miami Beach, Fla., the adulterated liquid injectable
silicone was injected into patients by the defendant--301(k).

DISPOSITION: An order for summary judgment and permanent injunction was
granted. (Inj. No. 1281; S. No. 92-577-012/0132; S.J. No. 14)


------------------------------------------------------------------------


MISCELLANEOUS ACTIONS

ACTION: Glaxo, Inc. v. Shalala, at Washington, D.C. (D.D.C.); Civil
Action No. 1:94CV01323.

CHARGED 6-16-94: The plaintiff, a company that markets the innovator
versions of two powerful corticosteroid drugs used in dermatology, filed
a complaint for injunctive relief requiring FDA to revoke approval of
abbreviated new drug applications held by Copley Pharmaceutical for
generic versions of these drugs. Plaintiff alleged that FDA had
improperly concluded that the generic drugs were bioequivalent to the
innovator products.

DISPOSITION: The plaintiff's motion for permanent injunction was denied.
Plaintiff notified the agency that it would not appeal the decision.
(Misc. No. 1038; S.J. No. 15) 

------------------------------------------------------------------------