FFnet June 13/05
Diets rich
in calcium and vitamin D may decrease risk of PMS
FSIS issues
final rule on nutrient content claims for meat and poultry products
Ten tips to
cut back the fat
Obesity in
middle age and future risk of dementia: a 27 year longitudinal population based
study
Notice to
the media - Health Canada
Algae as
health food
Biopharming
and the food system: Examining the potential benefits and risks
Glycemic
index: the next wave in nutrition?
how to subscribe
Diets
rich in calcium and vitamin D may decrease risk of PMS
June 13, 2005
JAMA and Archives Journals
CHICAGO – A diet rich in calcium and vitamin D may lower the risk of
developing premenstrual syndrome (PMS), according to a study in the June 13
issue of Archives of Internal Medicine, one of the JAMA/Archives journals.
While most women may experience mild emotional or physical premenstrual
symptoms, as many as eight to 20 percent of women experience symptoms severe
enough to meet the definition of premenstrual syndrome, characterized by
moderate to severe symptoms that substantially interfere with normal life
activities and interpersonal relationships, according to background information
in the article. Previous studies have suggested that calcium supplements and
vitamin D, a hormone that regulates the absorption of calcium, may reduce
premenstrual occurrence and severity.
Elizabeth R. Bertone-Johnson, Sc.D., of the University of Massachusetts,
Amherst, and colleagues compared the diets and supplement use of 1,057 women
aged 27 to 44 years who reported developing PMS over the course of 10 years to
1,968 women who reported no diagnosis of PMS or no or minimal premenstrual
symptoms in the same time period. The women, who participated in the Nurses
Health Study (NHS), all reported no PMS in 1991, at the beginning of the study
period. Their intake of calcium and vitamin D from diet and/or supplements was
calculated from food frequency and standard NHS questionnaires administered in
1991, 1995 and 1999.
"We observed a significantly lower risk of developing PMS in women with
high intakes of vitamin D and calcium from food sources, equivalent to about
four servings per day of skim or low-fat milk, fortified orange juice or low-fat
dairy foods such as yogurt," the authors write. "These dietary intakes
correspond to approximately 1,200 mg. of calcium and 400 IU of vitamin D from
food sources. While previous studies have observed the benefits of calcium
supplements for treating PMS, this is the first, to our knowledge, to suggest
that calcium and vitamin D may help prevent the initial development of
PMS."
"Our findings, together with those from several small randomized trials
that found calcium supplements to be effective in treating PMS, suggest that a
high intake of calcium and vitamin D may reduce the risk of PMS," the
authors conclude. "Clinical trials of this issue are warranted. In the
interim, given that calcium and vitamin D may also reduce risk of osteoporosis
and some cancers, clinicians may consider recommending these nutrients even for
younger women."
FSIS
issues final rule on nutrient content claims for meat and poultry products
June 10, 2005
FSIS Media Release
http://www.fsis.usda.gov/News_&_Events/NR_061005_01/index.asp
WASHINGTON - U.S. Department of Agriculture's Food Safety and Inspection Service
(FSIS) today announced a final rule amending the Federal meat and poultry
products inspection regulations to allow nutrient content claims in meat and
poultry product names. This action will help consumers maintain healthy diets by
providing detailed information they can use when making product choices. The
rule becomes effective January 1, 2008; however, establishments can voluntarily
adopt the rule's provisions upon publication.
By establishing the new standard, modifications of meat and poultry products
that have existing standards of identity and composition, such as fresh pork
sausage, ground beef, and turkey ham, will be possible if they conform to the
definition of a nutrient content claims. According to the standard,
manufacturers will now be able to use approved ingredients that are needed to
achieve a nutrient content claim, such as "low fat" and "reduced
sodium," to make substitute versions of traditional products, such as
"low fat pork sausage" and "reduced sodium chicken franks."
This rule will help further the development and availability of substitute
standardized products with reductions in certain ingredients that are of health
concern to consumers, such as fat, cholesterol and sodium. Additionally, the
rule expands the usefulness of current nutrient content labeling requirements to
provide consumers with a wider variety of healthy products that are accurately
labeled.
For further information, contact Dr. Robert Post, Director, Labeling and
Consumer Protection Staff, Office of Policy, Program, and Employee Development,
FSIS, USDA, Washington, D.C., 20250-3700, or by telephone at (202) 205-0279.
The final rule is available in the Federal Register and online on the FSIS
website at: http://www.fsis.usda.gov/regulations/
2005_interim_&_final_rules_index/.
Ten
tips to cut back the fat
June 9, 2005
Mayo Clinic
Weight-loss fads come and go. But no matter what you hear, limiting fat in your
diet, particularly saturated fat and trans fat -- is one of the most important
diet changes most Americans can make for optimum health.
The June issue of Mayo Clinic Health Letter offers 10 tips to help cut back on
fat:
Cool it -- Chill soups, gravies and stews, then skim off the fat that floats to
the top.
Buy skim -- Skim milk may taste thinner at first, but if you use it regularly,
your tastes should adapt. Try other dairy products such as fat-free yogurt,
reduced-fat or fat-free cheeses and low-fat or fat-free sour cream and cream
cheese.
Cook smart -- Limit using oils or butter for frying. Instead sauté or stir-fry
foods in a small amount of vegetable broth or cooking wine. Try baking,
broiling, steaming, poaching or grilling instead of frying.
No yolk -- With eggs, it’s the yolk that contains virtually all of the fat and
cholesterol. Try using egg substitutes. Or, in most recipes, you can use two egg
whites instead of one whole egg.
Cut butter and margarine -- Use apple, pumpkin or other fruit butters on breads
instead. Try fat-free, butter-flavored spreads or sprinkles. For baking,
substitute unsweetened applesauce, prune puree or a commercial baking substitute
for half of the butter, shortening or oil in your recipe.
Top it off -- Use fat-free salad dressing to add zip to salads or vegetables.
Plain, fat-free yogurt can be used in sauces for pasta, salads and sandwiches.
Top bagels with fat-free cream cheese.
Bean protein -- For a meal or two a week, use beans or legumes instead of meat
in a salad, soup or as the main dish.
Lean on meat -- Use extra-lean ground beef, ground chicken or ground turkey.
Instead of bacon, use Canadian bacon or prosciutto, a lean Italian ham. Buy beef
labeled “select” instead of “choice” or “prime.” Trim all fat from
meat cuts and remove chicken skin, before or after cooking.
Meat substitutes -- Meatless products, such as imitation hot dogs, bacon,
burgers and sausage are available at many grocery stores. They often contain
less fat -- especially saturated fat -- than is contained in an equivalent
portion of meat.
Room for dessert -- Use fat-free ice cream, frozen yogurt, sherbet or sorbet and
top with berries or a fat-free nondairy whipped topping.
This is a highlight from the June issue of Mayo Clinic Health Letter. You may
cite this publication as often as you wish. Also, you may reprint up to four
articles annually without cost. More frequent reprinting is allowed for a fee.
Mayo Clinic Health Letter attribution is required. Include the following
subscription information as your editorial policies permit: Call toll free for
subscription information, 800-333-9037, extension 9PR1.
Mayo Clinic Health Letter is an eight-page monthly newsletter of reliable,
accurate and practical information on today’s health and medical news. To
subscribe, please call toll free 800-333-9037, extension 9PR1.
Obesity
in middle age and future risk of dementia: a 27 year longitudinal population
based study
June 11, 2005
British Medical Journal
Vol. 330, No.7504
Rachel A Whitmer, gerontological epidemiologist1, Erica P Gunderson, obesity
epidemiologist1, Elizabeth Barrett-Connor, professor2, Charles P Quesenberry, Jr,
senior biostatistician1, Kristine Yaffe, associate professor3
1 Division of Research, Kaiser Permanente, Oakland, CA 94612, USA, 2 Department
of Epidemiology, University of California, La Jolla, CA, USA, 3 Department of
Psychiatry, University of California, San Francisco, CA, USA
Correspondence to: R A Whitmer raw@dor.kaiser.org
Objective To evaluate any association between obesity in middle age, measured by
body mass index and skinfold thickness, and risk of dementia later in life.
Design Analysis of prospective data from a multiethnic population based cohort.
Setting Kaiser Permanente Northern California Medical Group, a healthcare
delivery organisation.
Participants 10 276 men and women who underwent detailed health evaluations from
1964 to 1973 when they were aged 40-45 and who were still members of the health
plan in 1994.
Main outcome measures Diagnosis of dementia from January 1994 to April 2003.
Time to diagnosis was analysed with Cox proportional hazard models adjusted for
age, sex, race, education, smoking, alcohol use, marital status, diabetes,
hypertension, hyperlipidaemia, stroke, and ischaemic heart disease.
Results Dementia was diagnosed in 713 (6.9%) participants. Obese people (body
mass index 30) had a 74% increased risk of dementia (hazard ratio 1.74, 95%
confidence interval 1.34 to 2.26), while overweight people (body mass index
25.0-29.9) had a 35% greater risk of dementia (1.35, 1.14 to 1.60) compared with
those of normal weight (body mass index 18.6-24.9). Compared with those in the
lowest fifth, men and women in the highest fifth of the distribution of
subscapular or tricep skinfold thickness had a 72% and 59% greater risk of
dementia, respectively (1.72, 1.36 to 2.18, and 1.59, 1.24 to 2.04).
Conclusions Obesity in middle age increases the risk of future dementia
independently of comorbid conditions.
Notice
to the media - Health Canada
June 10, 2005
Canada News-Wire
OTTAWA - The Trans Fat Task Force will be holding a one-day consultation with
stakeholders in Ottawa. Health Canada and the Heart and Stroke Foundation of
Canada are co-chairing the task force aimed at developing recommendations and
strategies for reducing trans fats in the Canadian food supply to the lowest
level possible. The consultation will include presentations from various
industry stakeholders.
Task Force co-chairs Mary L'Abbé, Director, Bureau of Nutritional Sciences,
Health Canada, and Sally Brown, CEO, Heart and Stroke Foundation of Canada, will
be available to answer questions from media during breaks in the proceedings.
Media are required to sign in at the main registration desk upon arrival.
For more information about the Task Force, visit:
http://www.hc-sc.gc.ca/food-aliment/e_trans_fat.html
Algae
as health food
June 13, 2005
Deccan Herald
Mohan Krishna
http://www.deccanherald.com/
The Plant Cell Biotechnology Department at the Central Food Technology and
Research Institute (CFTRI) is, according to this story, involved in studies on
development of biotechnological processes on algae and higher plants for food
applications. Many procedures in plant biotechnology depend on the ability to
manoeuvre and grow plant cells in culture. Sometimes it is possible to generate
new kinds of plants by such manipulations. Cell walls can be stripped from cells
with digestive enzymes to produce protoplasts. Protoplasts of different species
can be mixed together and encouraged to fuse with special solutions. In this way
"somatic hybrids" can be formed.
The story says that in the area of algal biotechnology studies have been carried
out on mass cultivation of Spirulina and processing of algal biomass for use as
a source of protein, vitamins, minerals and nutraceuticals.
Spirulina technology has been transferred to several industries in India, which
produce algae of international quality. Several formulations of Spirulina are
already available in the Indian market.
The story adds that algae are also a good source of colourants such as
phycocyanin, which is a blue pigment of importance obtained from Spirulina.
Technology for downstream processing of phycocyanin is available for industrial
production. Phycocyanin is useful as a food and cosmetic colourant and also is
reported to be an anti-tumour compound.
Algae are rich sources of carotenoid pigments, which are of value in food and
pharmaceuticals. Plant Cell Biotechnology Department is also engaged in studies
on the mass cultivation of Dunaliella for -carotene and Haematococcus for
astaxanthin. -Carotene from natural sources has both cis and Trans isomers,
which are of value over the synthetic -carotene, which is only of all trans
forms.
'Spirulina' is a freshwater blue-green alga. It is a rich source of proteins,
vitamins and minerals. It is a health food, and has recently been gaining global
acceptance. Spirulina is approved by the Food and Drugs Agency, USA, World
Health Organisation and other international agencies as health food.
As a food Spirulina has been consumed in various forms over centuries in
different parts of the world. It contains a high amount of protein in an easily
digestible form. It also contains minerals, vitamins, essential fatty acids and
antioxidants that are not available to humans from any single food of vegetable
or animal source known so far.
Spirulina comprises Lysine, Cysteine, Methionine, Phenylalanine and Threonine-
essential amino acids that are not produced in humans and are not produced in
humans and are supplied through food. Spirulina is also a very rich source of
Vitamin B-12. It has 50 times higher iron content than Spinach. It contains high
amounts of (25 times higher than carrot and 100 times higher than papaya)
Beta-Carotene, the source of Vitamin 12.
Spirulina is helpful in preventing gastro enteric disturbances as it enhances
intestinal flora such as Lactobacillus and Bifidus bacteria. It is also known to
reduce the risks of infection by Eschericha Coli and Canrdida Albicans, two
virulent gastroenteritis pathogens. Spirulina by virtue of its fatty acid
contents is known to reduce Cholesterol. It contains anti-oxidant radicals that
scavenge highly reactive free radicals that are known to be involved in the
occurrence of many degenerative disorders such as cancer.
Biopharming
and the food system: Examining the potential benefits and risks
June 13, 2005
AgBioForum, The Journal of Agrobiotechnology
Aziz Elbehri
Biopharming (using crops as drug-producing bioreactors) offers tremendous
economic and health benefits stimulated by improving biotechnology methods.
However, these benefits must be weighed against the potential risks to the food
supply system and the costs of containing pharma crops to meet zero-tolerance
contamination requirements. A combination of strong and adaptable regulatory
oversight with technological innovations is required to achieve the twin goals
of capturing the benefits of biopharming and safeguarding the food system and
the environment. This paper examines the demand pull driving biopharming and the
risk and liabilities to agriculture and reviews the regulatory and technological
responses to the containment challenge faced by the food industry.
Introduction
Advances in genetic engineering now make it possible to use crops such as corn
and tobacco as drug factories. Plants used as bioreactors (biopharming) may soon
represent one of the most important developments in US agriculture, as
pharmaceutical and chemical industries use field crops to produce therapeutic
proteins, drugs, and vaccines. Pharmaceutical crops represent a radical
departure from the traditional idea of crops as a source of food, feed, and
fiber. The main driver for pharmaceutical crops comes from the biotech and
pharmaceutical industry, where there is a growing recognition of the vast
economic potential of using plants as platforms for drugs and therapeutic
compounds. However, biopharming also presents unique challenges for the food and
agricultural sector and federal regulators. The challenge arises from the strict
requirement—enforced by federal regulations—that plants grown for
pharmaceutical and industrial compounds (not approved for food and feed use)
must stay clear of the food system under a zero-tolerance standard. The key
issue is whether the economic payoffs from growing pharmaceutical plants
outweigh the costs associated with the risk of food system contamination.
The objectives of this article are to examine the demand forces from the biotech
industry behind biopharming and to assess the implications for food and
agriculture (i.e., the risks associated with growing these crops in open
fields). The paper also addresses the regulatory and technological responses to
maximize containment effectiveness and minimize contamination risks.
Drug Developments and the Appeal of Plant-Made Pharmaceuticals
The drug development process within the pharmaceutical industry has experienced
a significant transformation over the last two decades, driven largely by
biotechnology advances. Biotechnology played a key role in the expansion of
large-molecule drugs (as opposed to the small-molecule drugs manufactured by
chemical synthesis). Moreover, biotechnology further stimulated the trend toward
biological sources for drugs and therapeutics. These drugs, known as biologics,
include any protein, virus, therapeutic serum, vaccine, and blood component.
Another major impact of biotechnology was to enable the industry to move beyond
simple replication of human proteins (such as insulin or growth hormones).
Rather, new biopharmaceuticals are genetically engineered proteins targeting
some of the major illnesses in industrial countries, such as cancer,
cardiovascular, and infectious diseases—all critical to an expanding aging
population.
In the last two decades, there has been an unprecedented interest in proteins
and antibodies (as opposed to the traditional small-molecule drugs) stemming
from their potential to tackle a whole array of new diseases that have not been
addressed by small-molecule drugs. An advantage of these large-scale molecule
drugs is their ability to target diseases in a very specific manner, thus
maximizing efficacy while minimizing side effects. Hence, the market share of
biologic-derived drugs has been growing at a much higher rate because of their
perceived safety and effectiveness. For an industry that reached $430 billion of
global drug sales, the average industry growth of small-molecule drugs is around
7-8% over the next decade, compared to the 15% growth rate for the therapeutic
protein segment over the same period.
Building on developments in genetic engineering since the mid-1970s, the
biopharmaceutical era truly began in early 1980s, starting with the release of
the first transgenic drug, insulin, in 1982. Since then, biotechnology has had a
threefold impact on the manufacture of therapeutic proteins, which makes up a
significant segment of all biologically-derived drugs. There are currently 84
biopharmaceuticals on the market serving 60 million patients worldwide for a
cumulative market value of $20 billion.
According to the Pharmaceutical Research Medical Association, 500
biopharmaceuticals are estimated to be in clinical trials globally, 378 of which
are in earlier stages (Phase I and II), while 122 are in Phase III or awaiting
FDA approval. Using historical trends for drug approval rates, industry analysts
expect an average of six or seven new large-molecule drugs to reach the market
each year over the next several years. These monoclonal antibodies, which
require a large production capacity, are expected to make up about a third of
all new therapeutics. Building on recent successes and drug approvals, the
strong biotech therapeutics pipeline is creating a serious supply shortage for
drug manufacturing and inducing extended market disequilibrium, where demand far
outstrips supply.
Large-molecule therapeutics, which cannot be produced by chemical synthesis, are
traditionally manufactured either through microbial fermentation or more
commonly via mammalian cell culture. However, it is expected that current cell
culture facilities are unlikely to meet expected demand. There is already a
supply capacity crunch resulting from recently approved monoclonal antibodies,
which are primarily used for chronic diseases that often require high dosages.
These new drugs have stretched the fermentation production to full capacity.
Moreover, this supply-demand imbalance is expected to get worse in the future,
as more biotech therapeutics are approved. For example, each newly approved
monoclonal antibody requires 100,000 kg of production annually requiring new
fermentation capacity to be built. To meet the expected demand for new drug
production, more than three times the current production capacity may be
required. It is estimated that 20-50% of potential therapeutics industrywide
could be delayed due to the lack of manufacturing capacity.
A striking example of the drug supply shortage is the case of Enbrel—a biotech
drug, introduced by Immunex in 1998, that proved to be highly successful for
treating rheumatoid arthritis, which affects two million patients in the United
States. Enbrel is produced in 10,000-liter bioreactors of cultured Chinese
hamster cells; its success created a supply shortage starting in 2001. By March
2002, there was a waiting list of 13,000 patients. In response, Immunex began
rationing to pharmacies with the goal of maximizing the number of treated
patients. At the same time, Immunex launched a new production facility in
Germany, which will take up to five years to build and approve at a cost of $450
million. Meanwhile, the supply shortage is expected to continue into the near
future.
The Appeal of Plant-Made Pharmaceuticals
The current interest in pharmaceutical plants can be viewed both as a response
to these supply shortages and as an alternative platform to develop
therapeutics. Although many drug companies are pursuing additional fermentation
capacity to stave off the manufacturing crunch, other drug and biotech firms are
giving serious consideration to alternative platforms, including transgenic
plants and animals, insect cells, and even yeast cultures. Of these, plant-made
pharmaceuticals (PMPs) offer many advantages over mammalian cell culture
methods. First, there is the cost advantage. Industry estimates of unit costs of
therapeutic production with animal cell bioreactors range from as low as $106/g
of antibody to $650/g. The cost of producing the same amount of therapeutics
from plants is estimated to be four to five times lower than the mammalian cell
culture method. As an illustration, the production of 500 kg of monoclonal
antibodies would require an investment of US$450 million for a mammalian cell
culture fermentation facility and four to seven years to build and approve. By
contrast, the same amount of monoclonal antibodies could be produced on 500
acres of corn using a purification facility costing US$80 million and three to
five years to build and approve. The per-unit (gram) cost is $350-1,200/g
(depending on scale) for mammalian cell culture versus $80-250/g using
pharmaceutical corn.
A second advantage of PMPs is the large production capacity offered by
plants—in particular production scalability, which requires only that new
seeds be developed and that more acres be brought into production to meet
additional demand. A third advantage of PMPs is they are believed to be
inherently safer than recombinant proteins from microorganisms or cells. PMPs do
not carry potentially harmful human or animal viruses into the drug—a possible
limitation for drugs derived from mammalian cell cultures or animal milk.
Plant-Made Pharmaceuticals and Biopharming: An Emerging Industry
The technology for producing pharmaceuticals from plants has been available for
more than 16 years. The genetic engineering technology, referred to as the
Polymerase Chain Reaction (PCR), makes it possible to isolate the DNA sequence
that codes for a particular protein, reproduce many copies of that sequence, and
ultimately produce considerably larger quantities of particular proteins. The
process of developing and using plants to produce pharmaceutical compounds
consists of identifying the target protein and then identifying and isolating
the gene that codes for the protein. One approach is to insert the gene into a
plant vector, which enables transfer of new DNA into plant cell. Alternative
approaches use electrical discharge or biolistic particle bombardment to insert
the gene into the plant cell. Plant cells are then grown into callus and then
into seed-producing plants. The seeds are grown in a greenhouse or field, and
the protein is purified from leaf or seed material.
There are more than 20 biotech organizations that specialize in PMPs. Many of
these organizations (companies or universities) have specialized in one (or
more) crop of choice as a platform for therapeutic production. Among several of
the organizations currently active in PMP research and development is the
Missouri-based Chlorogen, Inc., which specializes in developing PMPs expressed
in tobacco, including vaccine for cholera, human serum albumin, and interferon
for hepatitis C, among others. Ventria Bioscience (California) uses rice to
develop PMPs such as lactoferrin and lysozyme—proteins used for human and
animal health applications. Meristem Therapeutics (France) uses corn to produce
gastric lipase (for treating of cystic fibrosis) and uses gene-modified alfalfa
to produce albumin (used in heart surgery). Another firm, Medicago (Canada), has
specialized in transgenic alfalfa to mass-produce hemoglobin for the growing
blood-bank market. Large Scale Biology Corp. (LSBC) uses the tobacco plant to
produce aprotinin (protease inhibitor), which is traditionally extracted from
cow lungs. Few of these protein therapeutics have yet to reach commercial stage;
many are at various stages of development and clinical testing, ranging from
preclinical stages to advanced or Phase III clinical stage levels.
Field testing of the pharmaceutical (and industrial) crops in the United States
has been taking place since the early 1990s. However, the pace and number of
these field-test trials have accelerated in recent years. According to APHIS
data, more than 325 sites of field trials in the United States were approved
from 1991 to 2004 for pharmaceutical, novel protein, and industrial enzymes. The
number of these trials has grown in the past few years, particularly in corn,
tobacco, soybeans, and rice. Although corn has dominated as the crop of choice,
there has been some drop in corn trials since 2003 as a result of a move toward
nonfood crops for pharmaceutical trials.
Open-Field Cultivation of Pharma Crops: The Containment Challenge
Genetically engineered crops grown to produce PMPs have little in common with
traditional agriculture. These pharmaceutical crops do not represent a new wave
of value-added agriculture. Rather, these crops represent open-air bioreactor
farming, a component of pharmaceutical and industrial enzyme manufacturing
process. Their cultivation in the field is predicated on the requirement of
total isolation and confinement from the food supply. The cost structure of
pharmaceutical crops is determined mostly by risk minimization requiring (a)
sophisticated risk management to avoid potential gene outflow and minimize
impact on nontarget organisms as well as workers' health; (b) identity
preservation based on a tight closed-loop system to avoid any possibility of
commingling with food supply; and (c) a set of quality-control procedures with a
tight chain of custody to satisfy the isolation and confinement requirement.
Genetically engineered pharmaceutical-producing crops require a permit from the
United States Department of Agriculture Animal and Plant Health Inspection
Service (USDA APHIS), which must include a containment plan for the plants
during the production, handling, and movement of plants in and out of the field.
APHIS reviews all plans for seed production, timing of pollination, harvest,
crop destruction, shipment, confinement, and the storage and use of equipment.
Field inspections may take place up to five times during the growing season
coinciding with critical times of production. APHIS issues a field test permit
either to an individual company or research institution who, in turn, may
subcontract with growers. Subcontracting farmers are also required to undergo
training in permit requirements and implementation.
The field confinement measures for pharmaceutical crops vary depending on the
biology of the plant. Self-pollinating crops (e.g., rice, barley), with their
heavy pollen, have isolation distances of 50 to several hundred feet. Isolation
for corn, with its wind-borne, relatively light pollen, is at least one mile.
Confinement guidelines also require a 50-foot fallow zone around pharma corn.
There is also a restriction on growing a food or feed crop on the same field the
following year. Pharma corn grown between one half and one mile must be planted
at least 28 days before or after any other corn within this distance. (This
temporal isolation minimizes the likelihood of pollen shed overlap and
cross-fertilization.) In addition to mandatory training for personnel, the use
of dedicated equipment for planting and harvesting must be approved by APHIS
along with dedicated facilities for storage of equipment and regulated articles
during the season.
The FDA also has domain over human drug and biological products produced from
pharmaceutical plants. The FDA considers pharmaceutical crops to be outdoor
manufacture sites and subject to regulatory scrutiny analogous to that applied
to conventional drug manufacturing facilities. The manufacturing process,
including field production, must follow the current Good Manufacturing
Procedures (GMP) to oversee greenhouse or field production practices. Basically,
the FDA expanded the GMP (traditionally applied to manufacturing facilities) to
the wide-open field for pharmaceutical crops. The aim is to insure consistent
manufacturing processes and product safety, purity, and potency. Prior to
commercial production of PMPs, the FDA must decide favorably on the safety and
efficacy of the pharmaceutical product, based upon clinical tests, chemistry
manufacturing and control, pharmacology/toxicology information, and an
acceptable inspection of the manufacturing facility.
Overall, the FDA's responsibility extends to the entire manufacture of the
biopharmaceuticals—from production to waste streams—so its role necessarily
complements and overlaps the role of APHIS at the field production stage.
Whereas APHIS regulates the growing and isolation of engineered crops, the FDA
regulates materials, equipment, and manufacturing processes—encompassing
everything from seed stock to packaging.
Federal regulatory rules are constantly evolving in response to advances in
science and technology. These standards have recently been revised. Moreover,
APHIS amended its regulations for genetically engineered plants that make drugs
and industrial compounds, requiring a standard permit for field testing rather
than notification (essentially an expedited permit) as previously allowed. In
2004, APHIS issued a public notice for proposed rule changes to its
biotechnology regulations. The proposed revisions would define
specific-risk-based categories for field testing for pharmaceutical and
industrial crops and consideration of environmental assessments in the issuance
of field-test permits. At the same time, both APHIS and FDA are reviewing
additional revisions, including specifying appropriate training standards the
use of third-party auditors and standard-setting organizations.
Biopharming and the Food Industry
Given the potential risks and liabilities associated with accidental commingling
with the food supply, and facing the daunting task of ensuring near-100%
containment, the food and the biotech industries have taken a precautionary
approach to pharmaceutical crops and support for risk-based regulations. The
Prodigene incident case in 2002 illustrates the type of risks facing the food
industry. In Nebraska, during the 2002 growing season, APHIS inspectors
discovered "pharmaceutical" volunteer corn growing in a soybean field.
The corn was from the previous year, when Prodigene had tested a pharmaceutical
corn to produce a swine vaccine. As a result, both the harvested soybeans (500
bushels) and the entire soybean load of 500,000 bushels in local elevator were
quarantined. In another accident in Iowa, the USDA forced Prodigene to burn 155
acres of conventional corn that may have cross-pollinated with some of the
company's pharmaceutical plants. In both cases, the infraction was viewed to
come from Prodigene's failure to adhere to permit protocols issued by APHIS.
Prodigene was fined US$250,000 and required to pay approximately $ 3 million for
the cleanup costs and disposal of contaminated corn and soybeans.
Although the quick discovery and resolution of the Prodigene incidence was
credited to the effectiveness of the existing regulations and oversight, the
incidents themselves provided the industry with a precedent for what could
happen in the future as more pharmaceutical crops are grown in open fields. It
is generally agreed that a 100% guarantee of zero contamination may be an
impossible goal to achieve under field growing conditions. This presents the
food industry with several challenges requiring consensual responses. More
immediately, a coalition of food industries seems to favor the inclusion of
food-safety assessment by event prior to issuing a permit. An implication of
such an approach is a better handle on risk in case the containment fails. In
practice, such an approach would tilt the current research and development away
from food crops (such as corn) in favor of nonfood crops (tobacco). This may
explain, in part, the drop in the number of pharmaceutical corn field trials,
beginning in 2003, and the concurrent rise of tobacco field trials.
In the medium and long term, improved confinement methods may require new and
innovative responses from the biotechnology industry itself. Many biotech
companies are currently pursuing production strategies that combine both
greenhouses and confined facilities with open fields. Other firms use plants in
completely closed facilities or greenhouses. An example is Medicago, which grows
biopharmaceutical alfalfa for therapeutic proteins in greenhouses. Under this
system, the company can produce up to 9 kg/year of protein with a unit value of
$10,000 per gram of protein using one 1,300-square-foot greenhouse.
However, when large quantities of pharmaceutical products are required or the
crops do not grow well in isolated systems, open-field production is necessary.
This tends to favor self-pollinated crops (e.g., soybeans, rice, or barley) at
the expense of open-pollinated crops (corn). There are other technology-based
options to ensure confinement. Among possible solutions is the use of pharma
plants with a "terminator gene" to ensure plant sterility or
engineering plants with visual markers for easy identification. For
wind-pollinated crops like corn, a precautionary practice currently in use is to
manually detassel corn (i.e., remove male flowers) and to plant rows of
nontransgenic corn to supply pollen for pharmaceutical plant and avoid pollen
drift beyond the pharma field. The preferred option from the food industry
perspective is the cultivation of pharma crops in locations that are far removed
from areas where food crops are grown, including possibly sourcing overseas.
Biopharming and Environmental Impact: Technological Solutions
Pharmaceutical crops may also present risks to the environment which include
potential safety issues linked to contamination with residual pesticides,
herbicides, and toxic plant metabolites. An additional concern is an altered
plant contaminating wild strains and human exposure to plant material containing
potent drugs. There is also the concern that transgenes will spread in the
environment and affect nontarget organisms. However, not all biopharmaceuticals
may be harmful, and many may be considered benign to nontarget organisms. This
is because many biopharmaceuticals are proteins with little or no biological
activity when ingested (e.g., vaccines and antibodies). Moreover, most proteins
are digestible and may pose little hazard of toxicity. Nevertheless,
biopharmaceuticals may be toxic in higher doses (e.g., anticoagulants, hormones,
and enzymes) or may persist longer in the environment (as in the case of
lipophilic drugs).
To limit environmental exposure, several technological solutions are being
pursued. One solution is to induce genes to produce therapeutic proteins only
after harvest. For example, to induce production of the protein
glucocerebrosidase, LSBC uses a nontransgenic tobacco plant cut at a given
height and sprayed under confined conditions with recombinant plant virus. An
alternative LSBC practice involves spraying tobacco plants in the field,
harvesting a few days later, and then purifying the protein. Another solution is
to use chloroplast transformation to limit gene flow. This approach consists of
introducing the gene not in the plant genome per se but rather in chloroplast
DNA, which enables the plant to produce the target protein but is not
transmitted to the seed. This is the approach followed by Chlorogen for tobacco.
Yet another option is to use plant genomes that are incompatible with nearby
related species.
Conclusions
Plant-made pharmaceuticals represent a significant development in the ongoing
biotechnology revolution. But are they inevitable? Certainly pharmaceutical
crops' lower production and capital costs and their greater production
flexibility give them a strong appeal as biofactories for drug development.
However, many scientific, regulatory, and economic hurdles remain. First, as a
new technology, PMPs have yet to fully demonstrate "proof of concept";
the suitability of green plants for protein manufacture is still not fully
resolved. Although the economics seem compelling, and all the trends so far
point toward feasibility, until these are approved by the FDA for commercial
use, there is still a large segment within the drug industry that is not yet
convinced that plant proteins will be as effective as animal-based proteins. A
second obstacle may come from new technological developments, which may or may
not continue to favor open-field cultivation compared to confined greenhouse
production. A third obstacle is that the cost advantage of PMPs could change in
favor of other production (expression) platforms with technological improvements
in fermentation processing or with animal-based transgenics (such as the use of
milk glands as the production medium).
Realistically, plants need to be viewed as just one possibility among many for
manufacturing therapeutic proteins. PMPs could evolve along several paths. They
could either dominate specific therapeutic protein markets or monopolize
biogenerics. Overall, plant transgenics will likely be the favorite expression
system with proteins that do not express well in traditional systems, are given
in large doses, or for which production costs make them too expensive to bring
to market.
Pharmaceutical crops may not require large amounts of acreage. The area needed
will depend on the potential demand for the pharmaceutical products. For
example, the production of the antibody against bacteria that cause tooth decay
would require 600 kilograms per year, which can be supplied by a single large
tobacco farm. On the other hand, using tobacco to produce human serum albumin
may require up to 45,000 acres of tobacco to meet world demand. However, for
pharma crops grown in open-field conditions in proximity to food crops, the
challenge of insuring 100% containment will be daunting. Consequently, one can
expect significant spillover effects on food-crop markets, in the likelihood of
contamination, particularly if PMPs are expressed via food crops such as corn or
rice.
For the biotech and drug industry, biopharming offers tremendous economic and
health benefits once the current cycle of product development reaches the
commercialization stage. However, for these benefits to be fully realized, the
central issue of risk to the food industry and the environment is a critical
requirement. Industrial and agricultural investments in biopharming must weigh
the size of economic payoffs from growing pharmaceuticals against the costs and
liabilities within the food supply system, including the potential loss to
export markets. A combination of strong and adaptable regulatory oversight with
technological solutions are required if the twin goals of realizing the full
potential of biopharming and safeguarding the food system and the environment
are to be met.
Author's Note
The views expressed here are those of the author and may not be attributed to
the Economic Research Service or the United States Department of Agriculture.
Glycemic
index: the next wave in nutrition?
June 10, 2005
Institute of Food Technologists (IFT)
Sales figures show U.S. consumers are learning that avoidance of an entire food
group is not healthy. Products and messages that consumers may now be primed to
accept in order to improve their nutrition is at the heart of scientific
presentations scheduled next month at the Institute of Food Technologists’
Annual Meeting + FOOD EXPO®.
Under scrutiny here Monday, July 18, will be the glycemic concept as a possible
next wave in nutrition. A panel of experts will explore food companies’
capabilities of modifying carbohydrate ingredients, the physiology and science
behind eating and its effect on glycemic levels, and the changing landscape that
manufacturers and consumers now navigate.
While the low-carb message is still heard, it is being restructured in
applicable and useful directions. This sets the stage for a new understanding of
carbs. For example, certain types extend satiety, lower insulin response and
reduce cholesterol.
This scientific review is one of dozens at the IFT Annual Meeting and Food Expo
that will focus on diet and health.
On Sunday, July 17, technology experts will offer alternatives for replacing
trans fats in foods, while other experts examine the hurdles of bringing
successful low-carb products to market. Topics the next day include fish
toxicology and safety, new dietary guidelines and advice for different segments
of the population including children. On Tuesday, foodservice’s focus on
reducing obesity, the industry’s advances toward reducing sodium in food, and
other health and nutrition topics will be examined.
Now in its 65th year, IFT Annual Meeting + FOOD EXPO® is the world’s single
largest annual scientific meeting and technical exposition of its kind,
regularly registering 20,000 attendees, nearly 1,000 exhibiting companies, and
more than 1,000 technical presentations. Rated among the largest shows in
America*, the meeting and expo delivers comprehensive, cutting-edge research and
opinion from food science-, technology-, marketing- and business-leaders.
In tandem with the IFT Food Safety & Quality Conference, this five-day
period is hailed as Food Science and Technology Week.
Much more detailed information is available online at http://www.am-fe.ift.org.
According to Tradeshow Week® 200 magazine.
Functional Foodnet is produced by the Food
Safety Network at the University of Guelph, and is supported by Agriculture and
Agri-Food Canada, Health Canada, the Ontario Ministry of Agriculture and Food,
AGCare, the Agricultural Adaptation Council (CanAdapt Program), National Pork
Board, ConAgra Foods, Inc., Food Safety & Security at Kansas State
University, Pfizer Animal Health and Blue Water Seafoods.The Food Safety
Network's national toll-free line for obtaining food safety information:
1-866-50-FSNET (1-866-503-7638).The Food Safety Network presents a unique
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