Integrated pest management

From Wikipedia, the free encyclopedia

An IPM boll weevil trap in a cotton field (Manning, South Carolina).

Integrated pest management (IPM), also known as integrated pest control
(IPC) is a broad-based approach that integrates practices for economic
control of pests. IPM aims to suppress pest populations below the economic
injury level (EIL). The UN's Food and Agriculture Organisation defines IPM as
"the careful consideration of all available pest control techniques and
subsequent integration of appropriate measures that discourage the
development of pest populations and keep pesticides and other interventions
to levels that are economically justified and reduce or minimize risks to
human health and the environment. IPM emphasizes the growth of a healthy
crop with the least possible disruption to agro-ecosystems and encourages
natural pest control mechanisms."[1] Entomologists and ecologists have
urged the adoption of IPM pest control since the 1970s.[2] IPM allows for safer
pest control.[clarification needed] This includes managing insects, plant
pathogens and weeds.

Globalization and increased mobility often allow increasing numbers of

invasive species to cross national borders.[3][4] IPM poses the least risks
while maximizing benefits and reducing costs.[5]

For their leadership in developing and spreading IPM worldwide, Perry

Adkisson and Ray F. Smith received the 1997 World Food Prize.[6]

Contents [hide]
1

History

Applications

Principles

Process

Southeast Asia

See also

References

Further reading

External links

History[edit]
Shortly after World War II, when synthetic insecticides became widely
available, entomologists in California developed the concept of "supervised
insect control".[7] Around the same time, entomologists in the US Cotton Belt
were advocating a similar approach. Under this scheme, insect control was
"supervised" by qualified entomologists and insecticide applications were
based on conclusions reached from periodic monitoring of pest and naturalenemy populations. This was viewed as an alternative to calendar-based
programs. Supervised control was based on knowledge of the ecology and
analysis of projected trends in pest and natural-enemy populations.

Supervised control formed much of the conceptual basis for the "integrated
control" that University of California entomologists articulated in the 1950s.
Integrated control sought to identify the best mix of chemical and biological
controls for a given insect pest. Chemical insecticides were to be used in the
manner least disruptive to biological control. The term "integrated" was thus
synonymous with "compatible." Chemical controls were to be applied only
after regular monitoring indicated that a pest population had reached a level
(the economic threshold) that required treatment to prevent the population
from reaching a level (the economic injury level) at which economic losses
would exceed the cost of the control measures.

IPM extended the concept of integrated control to all classes of pests and was
expanded to include all tactics. Controls such as pesticides were to be applied
as in integrated control, but these now had to be compatible with tactics for
all classes of pests. Other tactics, such as host-plant resistance and cultural
manipulations, became part of the IPM framework. IPM combined
entomologists, plant pathologists, nematologists and weed scientists.

In the United States, IPM was formulated into national policy in February 1972
when President Richard Nixon directed federal agencies to take steps to
advance the application of IPM in all relevant sectors. In 1979, President
Jimmy Carter established an interagency IPM Coordinating Committee to
ensure development and implementation of IPM practices.[8]

Applications[edit]
IPM is used in agriculture, horticulture, human habitations, preventive
conservation and general pest control, including structural pest management,
turf pest management and ornamental pest management.

Principles[edit]
An American IPM system is designed around six basic components:[9]

Acceptable pest levelsThe emphasis is on control, not eradication. IPM

holds that wiping out an entire pest population is often impossible, and the
attempt can be expensive and unsafe. IPM programmes first work to establish
acceptable pest levels, called action thresholds, and apply controls if those
thresholds are crossed. These thresholds are pest and site specific, meaning
that it may be acceptable at one site to have a weed such as white clover,
but not at another site. Allowing a pest population to survive at a reasonable
threshold reduces selection pressure. This lowers the rate at which a pest
develops resistance to a control, because if almost all pests are killed then
those that have resistance will provide the genetic basis of the future
population. Retaining a significant number of unresistant specimens dilutes
the prevalence of any resistant genes that appear. Similarly, the repeated use
of a single class of controls will create pest populations that are more
resistant to that class, whereas alternating among classes helps prevent this.
[citation needed]
Preventive cultural practicesSelecting varieties best for local growing
conditions and maintaining healthy crops is the first line of defense. Plant
quarantine and 'cultural techniques' such as crop sanitation are next, e.g.,
removal of diseased plants, and cleaning pruning shears to prevent spread of
infections. Beneficial fungi and bacteria are added to the potting media of
horticultural crops vulnerable to root diseases, greatly reducing the need for
fungicides.[citation needed]
MonitoringRegular observation is critically important. Observation is broken
into inspection and identification.[10] Visual inspection, insect and spore
traps, and other methods are used to monitor pest levels. Record-keeping is
essential, as is a thorough knowledge target pest behavior and reproductive
cycles. Since insects are cold-blooded, their physical development is
dependent on area temperatures. Many insects have had their development
cycles modeled in terms of degree-days. The degree days of an environment

determines the optimal time for a specific insect outbreak. Plant pathogens
follow similar patterns of response to weather and season.
Mechanical controlsShould a pest reach an unacceptable level, mechanical
methods are the first options. They include simple hand-picking, barriers,
traps, vacuuming and tillage to disrupt breeding.
Biological controlsNatural biological processes and materials can provide
control, with acceptable environmental impact, and often at lower cost. The
main approach is to promote beneficial insects that eat or parasitize target
pests. Biological insecticides, derived from naturally occurring
microorganisms (e.g.Bt, entomopathogenic fungi and entomopathogenic
nematodes), also fall in this category. Further 'biology-based' or 'ecological'
techniques are under evaluation.
Responsible useSynthetic pesticides are used as required and often only at
specific times in a pest's life cycle. Many newer pesticides are derived from
plants or naturally occurring substances (e.g.nicotine, pyrethrum and insect
juvenile hormone analogues), but the toxophore or active component may be
altered to provide increased biological activity or stability. Applications of
pesticides must reach their intended targets. Matching the application
technique to the crop, the pest, and the pesticide is critical. The use of lowvolume spray equipment reduces overall pesticide use and labor cost.
An IPM regime can be simple or sophisticated. Historically, the main focus of
IPM programmes was on agricultural insect pests.[11] Although originally
developed for agricultural pest management, IPM programmes are now
developed to encompass diseases, weeds and other pests that interfere with
management objectives for sites such as residential and commercial
structures, lawn and turf areas, and home and community gardens.

Process[edit]
IPM is the selection and use of pest control actions that will ensure favourable
economic, ecological and social consequences[12] and is applicable to most
agricultural, public health and amenity pest management situations. The IPM
process starts with monitoring, which includes inspection and identification,
followed by the establishment of economic injury levels. The economic injury
levels set the economic threshold level. That is the point when pest damage
(and the benefits of treating the pest) exceed the cost of treatment.[13] This
can also be an action threshold level for determining an unacceptable level
that is not tied to economic injury. Action thresholds are more common in
structural pest management and economic injury levels in classic agricultural
pest management. An example of an action threshold is one fly in a hospital

operating room is not acceptable, but one fly in a pet kennel would be
acceptable. Once a threshold has been crossed by the pest population action
steps need to be taken to reduce and control the pest. Integrated pest
management employ a variety of actions including cultural controls, including
physical barriers, biological controls, including adding and conserving natural
predators and enemies to the pest, and finally chemical controls or
pesticides. Reliance on knowledge, experience, observation and integration of
multiple techniques makes IPM appropriate for organic farming (excluding
synthetic pesticides). These may or may not include materials listed on the
Organic Materials Review Institute (OMRI)[14] Although the pesticides and
particularly insecticides used in organic farming and organic gardening are
generally safer than synthetic pesticides, they are not always more safe or
environmentally friendly than synthetic pesticides and can cause harm.[15]
For conventional farms IPM can reduce human and environmental exposure to
hazardous chemicals, and potentially lower overall costs.

Risk assessment usually includes four issues: 1) characterization of biological

control agents, 2) health risks, 3) environmental risks and 4) efficacy.[16]

Mistaken identification of a pest may result in ineffective actions. E.g., plant

damage due to over-watering could be mistaken for fungal infection, since
many fungal and viral infections arise under moist conditions.

Monitoring begins immediately, before the pest's activity becomes

significant. Monitoring of agricultural pests includes tracking soil/planting
media fertility and water quality. Overall plant health and resistance to pests
is greatly influenced by pH, alkalinity, of dissolved mineral and Oxygen
Reduction Potential. Many diseases are waterborne, spread directly by
irrigation water and indirectly by splashing.

Once the pest is known, knowledge of its lifecycle provides the optimal
intervention points.[17] For example, weeds reproducing from last year's
seed can be prevented with mulches and pre-emergent herbicide.

Pest-tolerant crops such as soybeans may not warrant interventions unless

the pests are numerous or rapidly increasing. Intervention is warranted if the
expected cost of damage by the pest is more than the cost of control. Health

hazards may require intervention that is not warranted by economic

considerations.

Specific sites may also have varying requirements. E.g., white clover may be
acceptable on the sides of a tee box on a golf course, but unacceptable in the
fairway where it could confuse the field of play.[18]

Possible interventions include mechanical/physical, cultural, biological and

chemical. Mechanical/physical controls include picking pests off plants, or
using netting or other material to exclude pests such as birds from grapes or
rodents from structures. Cultural controls include keeping an area free of
conducive conditions by removing waste or diseased plants, flooding,
sanding, and the use of disease-resistant crop varieties.[12] Biological
controls are numerous. They include: conservation of natural predators or
augmentation of natural predators, Sterile insect technique (SIT).[19]

Augmentation, inoculative release and inundative release are different

methods of biological control that affect the target pest in different ways.
Augmentative control includes the periodic introduction of predators.[20][21]
[22][23][24] With inundative release, predators are collected, mass-reared
and periodically released in large numbers into the pest area.[25][26][27]
This is used for an immediate reduction in host populations, generally for
annual crops, but is not suitable for long run use.[28] With inoculative release
a limited number of beneficial organisms are introduced at the start of the
growing season. This strategy offers long term control as the organism's
progeny affect pest populations throughout the season and is common in
orchards.[28][29] With seasonal inoculative release the beneficials are
collected, mass-reared and released seasonally to maintain the beneficial
population. This is commonly used in greenhouses.[29] In America and other
western countries, inundative releases are predominant, while Asia and the
eastern Europe more commonly use inoculation and occasional introductions.
[28]

The Sterile insect technique (SIT) is an Area-Wide IPM program that

introduces sterile male pests into the pest population to trick females into
(unsuccessful) breeding encounters, providing a form of birth control and
reducing reproduction rates.[19] The biological controls mentioned above
only appropriate in extreme cases, because in the introduction of new

species, or supplementation of naturally occurring species can have

detrimental ecosystem effects. Biological controls can be used to stop
invasive species or pests, but they can become an introduction path for new
pests.[30]

Chemical controls include horticultural oils or the application of insecticides

and herbicides. A Green Pest Management IPM program uses pesticides
derived from plants, such as botanicals, or other naturally occurring
materials.

Pesticides can be classified by their modes of action. Rotating among

materials with different modes of action minimizes pest resistance.[12]

Evaluation is the process of assessing whether the intervention was effective,

whether it produced unacceptable side effects, whether to continue, revise or
abandon the program.[31]

Southeast Asia[edit]
The Green Revolution of the 1960s and '70s introduced sturdier plants that
could support the heavier grain loads resulting from intensive fertilizer use.
Pesticide imports by 11 Southeast Asian countries grew nearly sevenfold in
value between 1990 and 2010, according to FAO statistics, with disastrous
results. Rice farmers become accustomed to spraying soon after planting,
triggered by signs of the leaf folder moth, which appears early in the growing
season. It causes only superficial damage and doesn't reduce yields. In 1986,
Indonesia banned 57 pesticides and completely stopped subsidizing their use.
Progress was reversed in the 2000s, when growing production capacity,
particularly in China, reduced prices. Rice production in Asia more than
doubled. But it left farmers believing more is betterwhether it's seed,
fertilizer, or pesticides.[32]

The brown planthopper (Nilaparvata lugens), the farmers' main target, has
become increasingly resistant. Since 2008, outbreaks have devastated rice
harvests throughout Asia, but not in the Mekong Delta. Reduced spraying
allowed natural predators to neutralize planthoppers in Vietnam. In 2010 and
2011, massive planthopper outbreaks hit 400,000 hectares of Thai rice fields,

causing losses of about $64 million. The Thai government is now pushing the
"no spray in the first 40 days" approach.[32]

By contrast early spraying kills frogs, spiders, wasps and dragonflies that prey
on the later-arriving and dangerous planthopper and produced resistant
strains. Planthoppers now require pesticide doses 500 times greater than
originally. Overuse indiscriminately kills beneficial insects and decimates bird
and amphibian populations. Pesticides are suspected of harming human
health and became a common means for rural Asians to commit suicide.[32]

In 2001, scientists challenged 950 Vietnamese farmers to try IPM. In one plot,
each farmer grew rice using their usual amounts of seed and fertilizer,
applying pesticide as they chose. In a nearby plot, less seed and fertilizer
were used and no pesticides were applied for 40 days after planting. Yields
from the experimental plots was as good or better and costs were lower,
generating 8% to 10% more net income. The experiment led to the "three
reductions, three gains" campaign, claiming that cutting the use of seed,
fertilizer and pesticide would boost yield, quality and income. Posters,
leaflets, TV commercials and a 2004 radio soap opera that featured a rice
farmer who gradually accepted the changes. It didn't hurt that a 2006
planthopper outbreak hit farmers using insecticides harder than those who
didn't. Mekong Delta farmers cut insecticide spraying from five times per crop
cycle to zero to one.

The Plant Protection Center and the International Rice Research Institute
(IRRI) have been encouraging farmers to grow flowers, okra and beans on rice
paddy banks, instead of stripping vegetation, as was typical. The plants
attract bees and a tiny wasp that eats planthopper eggs, while the
vegetables diversify farm incomes.[32]

Agriculture companies offer bundles of pesticides with seeds and fertilizer,

with incentives for volume purchases. A proposed law in Vietnam requires
licensing pesticide dealers and government approval of advertisements to
prevent exaggerated claims. Insecticides that target other pests, such as
Scirpophaga incertulas (stem borer), the larvae of moth species that feed on
rice plants allegedly yield gains of 21% with proper use.[32]
--------------------------------

Rodenticide
From Wikipedia, the free encyclopedia
"Rat poison" redirects here. For the window manager, see ratpoison.

Typical rat poison bait station (Germany, 2010

Rodenticides, colloquially rat poison, are typically non-specific pest control
chemicals made and sold for the purpose of killing rodents.

Some rodenticides are lethal after one exposure while others require more
than one. Rodents are disinclined to gorge on an unknown food (perhaps
reflecting an adaptation to their inability to vomit), preferring to sample, wait
and observe whether it makes them or other rats sick.[1][2] This
phenomenon of bait shyness or poison shyness is the rationale for poisons
that kill only after multiple doses.

Besides being directly toxic to the mammals that ingest them, including dogs,
cats, and humans, many rodenticides present a secondary poisoning risk to
animals that hunt or scavenge the dead corpses of rats.

Contents [hide]
1

Chemical preparations

1.1

Anticoagulants

1.2

Metal phosphides

1.3

Hypercalcemia

1.4

Other

1.5

Combinations

Alternatives

Non-target issues

3.1

Secondary poisoning and risks to wildlife

3.2

Proposed US legislation change

Notable rat eradications

See also

References

Further reading

External links

Chemical preparations[edit]
Anticoagulants[edit]
Anticoagulants are defined as chronic (death occurs one to two weeks after
ingestion of the lethal dose, rarely sooner), single-dose (second generation)
or multiple-dose (first generation) rodenticides, acting by effective blocking of
the vitamin K cycle, resulting in inability to produce essential blood-clotting
factors mainly coagulation factors II (prothrombin) and VII (proconvertin).

In addition to this specific metabolic disruption, massive toxic doses of 4hydroxycoumarin, 4-thiochromenone and indandione anticoagulants cause
damage to tiny blood vessels (capillaries), increasing their permeability,
causing diffuse internal bleeding. These effects are gradual, developing over
several days. In the final phase of the intoxication, the exhausted rodent
collapses due to hemorrhagic shock or severe anemia and dies calmly. The
question of whether the use of these rodenticides can be considered humane
has been raised.[3]

The main benefit of anticoagulants over other poisons is that the time taken
for the poison to induce death means that the rats do not associate the
damage with their feeding habits.

First generation rodenticidal anticoagulants generally have shorter

elimination half-lives,[4] require higher concentrations (usually between
0.005% and 0.1%) and consecutive intake over days in order to accumulate
the lethal dose, and are less toxic than second generation agents.
Second generation agents are far more toxic than first generation. They are
generally applied in lower concentrations in baits usually on the order of
0.001% to 0.005% are lethal after a single ingestion of bait and are also

effective against strains of rodents that became resistant to first generation

anticoagulants; thus, the second generation anticoagulants are sometimes
referred to as "superwarfarins".[5]
Class Examples
Coumarins/4-hydroxycoumarins
First generation: warfarin, coumatetralyl
Second generation: difenacoum, brodifacoum,[6] flocoumafen and
bromadiolone.
1,3-indandiones

diphacinone, chlorophacinone,[7] pindone

These are harder to group by generation. According to some sources, the

indandiones are considered second generation.[8] However, according to the
U.S. Environmental Protection Agency, examples of first generation agents
include chlorophacinone and diphacinone.[6]

4-thiochromenones Difethialone is considered a second generation

anticoagulant rodenticide .[9]
Indirect
Sometimes, anticoagulant rodenticides are potentiated by an
antibiotic or bacteriostatic agent, most commonly sulfaquinoxaline. The aim
of this association is that the antibiotic suppresses intestinal symbiotic
microflora, which are a source of vitamin K. Diminished production of vitamin
K by the intestinal microflora contributes to the action of anticoagulants.
Added vitamin D also has a synergistic effect with anticoagulants.
Vitamin K1 has been suggested, and successfully used, as antidote for pets or
humans accidentally or intentionally exposed to anticoagulant poisons. Some
of these poisons act by inhibiting liver functions and in advanced stages of
poisoning, several blood-clotting factors are absent, and the volume of
circulating blood is diminished, so that a blood transfusion (optionally with
the clotting factors present) can save a person who has been poisoned, an
advantage over some older poisons.

Metal phosphides[edit]

Rat poison vendor's stall at a market in Linxia City, China

Metal phosphides have been used as a means of killing rodents and are

considered single-dose fast acting rodenticides (death occurs commonly

within 13 days after single bait ingestion). A bait consisting of food and a
phosphide (usually zinc phosphide) is left where the rodents can eat it. The
acid in the digestive system of the rodent reacts with the phosphide to
generate the toxic phosphine gas. This method of vermin control has possible
use in places where rodents are resistant to some of the anticoagulants,
particularly for control of house and field mice; zinc phosphide baits are also
cheaper than most second-generation anticoagulants, so that sometimes, in
the case of large infestation by rodents, their population is initially reduced
by copious amounts of zinc phosphide bait applied, and the rest of population
that survived the initial fast-acting poison is then eradicated by prolonged
feeding on anticoagulant bait. Inversely, the individual rodents, that survived
anticoagulant bait poisoning (rest population) can be eradicated by prebaiting them with nontoxic bait for a week or two (this is important to
overcome bait shyness, and to get rodents used to feeding in specific areas
by specific food, especially in eradicating rats) and subsequently applying
poisoned bait of the same sort as used for pre-baiting until all consumption of
the bait ceases (usually within 24 days). These methods of alternating
rodenticides with different modes of action gives actual or almost 100%
eradications of the rodent population in the area, if the
acceptance/palatability of baits are good (i.e., rodents feed on it readily).

Zinc phosphide is typically added to rodent baits in a concentration of 0.75%

to 2.0%. The baits have strong, pungent garlic-like odor due to the phosphine
liberated by hydrolysis. The odor attracts (or, at least, does not repel)
rodents, but has an repulsive effect on other mammals. Birds, notably wild
turkeys, are not sensitive to the smell, and will feed on the bait, and thus
become collateral damage.

The tablets or pellets (usually aluminium, calcium or magnesium phosphide

for fumigation/gassing) may also contain other chemicals which evolve
ammonia, which helps to reduce the potential for spontaneous combustion or
explosion of the phosphine gas.

Metal phosphides do not accumulate in the tissues of poisoned animals, so

the risk of secondary poisoning is low.

Before the advent of anticoagulants, phosphides were the favored kind of rat

poison. During World War II, they came into use in United States because of
shortage of strychnine due to the Japanese occupation of the territories
where the strychnine tree is grown. Phosphides are rather fast-acting rat
poisons, resulting in the rats dying usually in open areas, instead of in the
affected buildings.

Phosphides used as rodenticides include:

aluminium phosphide (fumigant only)

calcium phosphide (fumigant only)
magnesium phosphide (fumigant only)
zinc phosphide (bait only)
Hypercalcemia[edit]
Calciferols (vitamins D), cholecalciferol (vitamin D3) and ergocalciferol
(vitamin D2) are used as rodenticides. They are toxic to rodents for the same
reason they are important to humans: they affect calcium and phosphate
homeostasis in the body. Vitamins D are essential in minute quantities (few
IUs per kilogram body weight daily, only a fraction of a milligram), and like
most fat soluble vitamins, they are toxic in larger doses, causing
hypervitaminosis. If the poisoning is severe enough (that is, if the dose of the
toxin is high enough), it leads to death. In rodents that consume the
rodenticidal bait, it causes hypercalcemia, raising the calcium level, mainly
by increasing calcium absorption from food, mobilising bone-matrix-fixed
calcium into ionised form (mainly monohydrogencarbonate calcium cation,
partially bound to plasma proteins, [CaHCO3]+), which circulates dissolved in
the blood plasma. After ingestion of a lethal dose, the free calcium levels are
raised sufficiently that blood vessels, kidneys, the stomach wall and lungs are
mineralised/calcificated (formation of calcificates, crystals of calcium
salts/complexes in the tissues, damaging them), leading further to heart
problems (myocardial tissue is sensitive to variations of free calcium levels,
affecting both myocardial contractibility and excitation propagation between
atrias and ventriculas), bleeding (due to capillary damage) and possibly
kidney failure. It is considered to be single-dose, cumulative (depending on
concentration used; the common 0.075% bait concentration is lethal to most
rodents after a single intake of larger portions of the bait) or sub-chronic
(death occurring usually within days to one week after ingestion of the bait).
Applied concentrations are 0.075% cholecalciferol and 0.1% ergocalciferol
when used alone, wihich can kill a rodent or a rat.

There is an important feature of calciferols toxicology, that they are

synergistic with anticoagulant toxicants, that means, that mixtures of
anticoagulants and calciferols in same bait are more toxic than a sum of
toxicities of the anticoagulant and the calciferol in the bait, so that a massive
hypercalcemic effect can be achieved by a substantially lower calciferol
content in the bait, and vice versa, a more pronounced
anticoagulant/hemorrhagic effects are observed if the calciferol is present.
This synergism is mostly used in calciferol low concentration baits, because
effective concentrations of calciferols are more expensive than effective
concentrations of most anticoagulants.

The first application of a calciferol in rodenticidal bait was in the Sorex

product Sorexa D (with a different formula than today's Sorexa D), back in the
early 1970s, which contained 0.025% warfarin and 0.1% ergocalciferol.
Today, Sorexa CD contains a 0.0025% difenacoum and 0.075% cholecalciferol
combination. Numerous other brand products containing either 0.075-0.1%
calciferols (e.g. Quintox) alone or alongside an anticoagulant are marketed.

The Merck Veterinary Manual states the following:

Although this rodenticide [cholecalciferol] was introduced with claims that it

was less toxic to nontarget species than to rodents, clinical experience has
shown that rodenticides containing cholecalciferol are a significant health
threat to dogs and cats. Cholecalciferol produces hypercalcemia, which
results in systemic calcification of soft tissue, leading to renal failure, cardiac
abnormalities, hypertension, CNS depression and GI upset. Signs generally
develop within 18-36 hours of ingestion and can include depression, anorexia,
polyuria and polydipsia. As serum calcium concentrations increase, clinical
signs become more severe. ... GI smooth muscle excitability decreases and is
manifest by anorexia, vomiting and constipation. ... Loss of renal
concentrating ability is a direct result of hypercalcemia. As hypercalcemia
persists, mineralization of the kidneys results in progressive renal
insufficiency."[10]

Additional anticoagulant renders the bait more toxic to pets as well as

human. Upon single ingestion, solely calciferol-based baits are considered
generally safer to birds than second generation anticoagulants or acute

toxicants. A specific antidote for calciferol intoxication is calcitonin, a

hormone that lowers the blood levels of calcium. The therapy with
commercially available calcitonin preparations is, however, expensive.

Other[edit]

Civilian Public Service worker distributes rat poison for typhus control in
Gulfport, Mississippi, ca. 1945.
Other chemical poisons include:

ANTU (-naphthylthiourea; specific against Brown rat, Rattus norvegicus)

Arsenic trioxide
Barium carbonate
Chloralose (a narcotic prodrug)
Crimidine (inhibits metabolism of vitamin B6)
1,3-Difluoro-2-propanol ("Gliftor")
Endrin (organochlorine insecticide, used in the past for extermination of voles
in fields)
Fluoroacetamide ("1081")
Phosacetim (a delayed-action organophosphate)
White phosphorus
Pyrinuron (an urea derivative)
Scilliroside
Sodium fluoroacetate ("1080")
Strychnine (A naturally occurring convulsant and stimulant)
Tetramethylenedisulfotetramine ("tetramine")
Thallium sulfate
Nitrophenols like bromethalin and 2,4-dinitrophenol (cause high fever and

brain swelling, no known antidote)

Zyklon B/Uragan D2 (hydrogen cyanide gas absorbed in an inert carrier)
Combinations[edit]
In some countries, fixed three-component rodenticides, i.e., anticoagulant +
antibiotic + vitamin D, are used. Associations of a second-generation
anticoagulant with an antibiotic and/or vitamin D are considered to be
effective even against most resistant strains of rodents, though some second
generation anticoagulants (namely brodifacoum and difethialone), in bait
concentrations of 0.0025% to 0.005% are so toxic that resistance is unknown,
and even rodents resistant to other rodenticides are reliably exterminated by
application of these most toxic anticoagulants.

Alternatives[edit]
More environmentally-safe preparations, such as powdered corn cob, have
been developed and were approved in the EU and patented in the US in 2013.
These preparations rely on dehydration to cause death.[11][12]

Non-target issues[edit]
Secondary poisoning and risks to wildlife[edit]
One of the potential problems when using rodenticides is that dead or
weakened rodents may be eaten by other wildlife, either predators or
scavengers. Members of the public deploying rodenticides may not be aware
of this or may not follow the product's instructions closely enough.

The faster a rodenticide acts, the more critical this problem may be. For the
fast-acting rodenticide bromethalin, for example, there is no diagnostic test
or antidote.[13]

This has led environmental researchers to conclude that low strength, long
duration rodenticides (generally first generation anticoagulants) are the best
balance between maximum effect and minimum risk.[14]

Proposed US legislation change[edit]

In 2008, after assessing human health and ecological effects, as well as

benefits,[6] the US Environmental Protection Agency (EPA) announced
measures to reduce risks associated with ten rodenticides. New restrictions
by sale and distribution restrictions, minimum package size requirements,
use site restriction, and tamper resistant products would have taken effect in
2011. The regulations were delayed pending a legal challenge by
manufacturer Reckitt-Benkiser.[13]

Notable rat eradications[edit]

The entire rat populations of several islands have been eradicated, most
notably Campbell Island, New Zealand (11,300 ha),[15] Hawadax Island,
Alaska (formerly known as Rat Island, 2,670 ha)[16] and Canna, Scotland
(1,030 ha, declared rat-free in 2008).[17]

Alberta, Canada, through a combination of climate and control, is believed to

be rat-free.[18]
---------------------------Maximum Residue Limit
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Pesticide residues on crops are monitored through the use of Maximum
Residue Limits (MRL), which are based on the analysis of the quantity of a
given chemical remaining on food product samples. The MRL is usually
determined by repeated (on the order of 10) field trials, where the crop has
been treated according to good agricultural practice (GAP) and an

appropriate pre harvest interval or withholding period has elapsed. For many
pesticides this is set at the Limit of Determination (LOD) since only major
pesticides have been evaluated and understanding of Acceptable daily intake
(ADI) is incomplete (i.e. producers or public bodies have not submitted MRL
data often because these were not required in the past). LOD can be
considered a measure of presence/absence, but certain residues may not be
quantifiable at very low levels. For this reason the limit of quantification (LOQ)
is often used instead of the LOD. As a rule of thumb the LOQ is approximately
two times the LOD. For substances that are not included in any of the
annexes in EU regulations, a default MRL of 0.01 mg/kg normally applies.

It follows that adoption of GAP at the farm level must be a priority, and
includes the withdrawal of obsolete pesticides. With increasingly sensitive
detection equipment, a certain amount of pesticide residue will often be
measured following field use. In the current regulatory environment, it would
be wise for cocoa producers to focus only on pest control agents that are
permitted for use in the EU and US. It should be stressed that MRLs are set on
the basis of observations and not on ADIs. If MRL of some drug is not known it
is calculated by the formula: MRL= ADI*W/MDI*100*(safety factor)

Ornamental Crops[edit]
In some cases in the EU MRL's are also used for ornamental produce, and
checked against MRL's for food crops. While this is a sound approach for the
general environmental impact, it doesn't reflect potential exposure of people
handling ornamentals. A swap test can eliminate this gap. MRL's for
ornamental produce can sometimes result in a conflicting outcome because
of the absence of pre harvest intervals (PHI) or withholding periods for
ornamentals, specifically in crops where harvesting is continuous, like roses.
This happens when a grower is following the label recommendations and the
produce is sampled shortly after.
------------------Occupational Safety and Health Administration
From Wikipedia, the free encyclopedia
Not to be confused with EU-OSHA, the European Agency for Safety and

Health at Work. For other uses, see OSHA (disambiguation).

Occupational Safety and Health Administration
US-OSHA-Logo.svg
Agency overview
Formed

1971

Jurisdiction

Federal government of the United States

Headquarters
Employees

Washington, D.C.

2,265 (2015)[1]

Annual budget

$552 million (2015)[1]

Agency executive
David Michaels, Assistant Secretary
Parent department United States Department of Labor
Website

www.osha.gov

The Occupational Safety and Health Administration (OSHA) is an agency of

the United States Department of Labor. Congress established the agency
under the Occupational Safety and Health Act, which President Richard M.
Nixon signed into law on December 29, 1970. OSHA's mission is to "assure
safe and healthful working conditions for working men and women by setting
and enforcing standards and by providing training, outreach, education and
assistance".[2] The agency is also charged with enforcing a variety of
whistleblower statutes and regulations. OSHA is currently headed by
Assistant Secretary of Labor David Michaels.

Contents [hide]
1

History

OSHA coverage

2.1

Private sector employers

2.2

State and local governments

2.3

Federal government agencies

2.4

Not covered under the OSHA Act

Rights and responsibilities under OSHA law

Health and safety standards

Enforcement

Recordkeeping requirements

Whistleblower protection

Compliance assistance

Controversy

10

See also

11

References

12

External links

History[edit]
OSHA officially formed on April 28, 1971, the date that the OSH Act became
effective.[3] George Guenther was appointed as the agency's first director.

OSHA has a number of training, compliance assistance, and health and safety
recognition programs throughout its history. The OSHA Training Institute,
which trains government and private sector health and safety personnel,
began in 1972.[3] In 1978, the agency began a grantmaking program, now
called the Susan Harwood Training Grant Program, to train workers and
employers in reducing workplace hazards.[3] OSHA started the Voluntary
Protection Programs in 1982, which allow employers to apply as "model
workplaces" to achieve special designation if they meet certain requirements.
[3]

OSHA coverage[edit]
The OSHA Act covers most private sector employers and their workers, in
addition to some public sector employers and workers in the 50 states and
certain territories and jurisdictions under federal authority. Those jurisdictions
include the District of Columbia, Puerto Rico, the Virgin Islands, American
Samoa, Guam, Northern Mariana Islands, Wake Island, Johnston Island, and
the Outer Continental Shelf Lands as defined in the Outer Continental Shelf

Lands Act.

Private sector employers[edit]

OSHA covers most private sector employers in all 50 states, the District of
Columbia, and other U.S. jurisdictionseither directly through federal OSHA
or through an OSHA approved state plan.

State plans are OSHA-approved job safety and health programs operated by
individual states instead of federal OSHA. Federal OSHA approves and
monitors all state plans and provides as much as fifty percent of the funding
for each program. State-run safety and health programs are required to be at
least as effective as the federal OSHA program.

The following 22 states or territories have OSHA-approved state programs:

Alaska, Arizona, California, Hawaii, Indiana, Iowa, Kentucky, Maryland,
Michigan, Minnesota, Nevada, New Mexico, North Carolina, Oregon, Puerto
Rico, South Carolina, Tennessee, Utah, Vermont, Virginia, Washington, and
Wyoming.[4]

Federal OSHA provides coverage to certain workplaces specifically excluded

from a states plan for example, work in maritime industries or on military
bases.

State and local governments[edit]

Workers at state and local government agencies are not covered by federal
OSHA, but have OSH Act protections if they work in those states that have an
OSHA-approved state program. OSHA rules also permit states and territories
to develop plans that cover only public sector (state and local government)
workers. In these cases, private sector workers and employers remain under
federal OSHA jurisdiction. Five additional states and one U.S. territory have
OSHA approved state plans that cover public sector workers only:
Connecticut, Illinois, Maine, New Jersey, New York, and the Virgin Islands.

Federal government agencies[edit]

OSHAs protection applies to all federal agencies. Section 19 of the OSH Act
makes federal agency heads responsible for providing safe and healthful
working conditions for their workers. OSHA conducts inspections of federal
facilities in response to workers reports of hazards and under programs that
target high hazard federal workplaces.[5]

Federal agencies must have a safety and health program that meets the
same standards as private employers. OSHA issues virtual fines to federal
agencies following an inspection where violations are found, OSHA issues a
press release stating the size the fine would be if the federal agency were a
private sector employer. Under a 1998 amendment, the OSHA Act covers the
U.S. Postal Service the same as any private sector employer.

Not covered under the OSHA Act[edit]

The self-employed; immediate family members of farm employers; and
workplace hazards regulated by another federal agency (for example, the
Mine Safety and Health Administration, the Department of Energy, or Coast
Guard).[6]

Rights and responsibilities under OSHA law[edit]

Employers have the responsibility to provide a safe workplace.[7]

By law, employers must provide their workers with a workplace that does not
have serious hazards and must follow all OSHA safety and health standards.
Employers must find and correct safety and health problems. OSHA further
requires that employers must first try to eliminate or reduce hazards by
making feasible changes in working conditions rather than relying on
personal protective equipment such as masks, gloves, or earplugs. Switching
to safer chemicals, enclosing processes to trap harmful fumes, or using
ventilation systems to clean the air are examples of effective ways to
eliminate or reduce risks.

Barry Salerno Talks with a Homeowner in Washington, Ill. about Fall Hazards &
Unstable Surfaces

Employers must also:

Inform workers about chemical hazards through training, labels, alarms, colorcoded systems, chemical information sheets and other methods.
Provide safety training to workers in a language and vocabulary they can
understand.[8]
Keep accurate records of work-related injuries and illnesses.
Perform tests in the workplace, such as air sampling, required by some OSHA
standards.
Provide required personal protective equipment at no cost to workers.
(Employers must pay for most types of required personal protective
equipment.)[9][10]
Provide hearing exams or other medical tests when required by OSHA
standards.
Post OSHA citations and annually post injury and illness summary data where
workers can see them.[11][12]
Notify OSHA within eight hours of a workplace fatality. Notify OSHA within 24
hours of all work-related inpatient hospitalizations, all amputations, and all
losses of an eye (1-800-321-OSHA [6742]).
Prominently display the official OSHA Job Safety and Health Its the Law
poster[13] that describes rights and responsibilities under the OSH Act.
Not retaliate or discriminate against workers[14] for using their rights under
the law, including their right to report a work-related injury or illness.
Workers have the right to:[15]

Working conditions that do not pose a risk of serious harm.

File a confidential complaint with OSHA to have their workplace inspected.
[16]
Receive information and training about hazards, methods to prevent harm,
and the OSHA standards that apply to their workplace. The training must be
done in a language and vocabulary workers can understand.
Receive copies of records of work-related injuries and illnesses that occur in

their workplace.
Receive copies of the results from tests and monitoring done to find and
measure hazards in their workplace.
Receive copies of their workplace medical records.
Participate in an OSHA inspection and speak in private with the inspector.
File a complaint with OSHA if they have been retaliated or discriminated
against by their employer as the result of requesting an inspection or using
any of their other rights under the OSH Act.
File a complaint if punished or retaliated against for acting as a
whistleblower under the 21 additional federal laws for which OSHA has
jurisdiction.[14]
Temporary workers must be treated like permanent employees. Staffing
agencies and host employers share a joint accountability over temporary
workers. Both entities are therefore bound to comply with workplace health
and safety requirements and to ensure worker safety and health. OSHA could
hold both the host and temporary employers responsible for the violation of
any condition.[17]

Health and safety standards[edit]

The Occupational Safety and Health Act grants OSHA the authority to issue
workplace health and safety regulations. These regulations include limits on
hazardous chemical exposure, employee access to hazard information,
requirements for the use of personal protective equipment, and requirements
to prevent falls and hazards from operating dangerous equipment.

OSHAs current Construction, General Industry, Maritime and Agriculture

standards[18] are designed to protect workers from a wide range of serious
hazards. Examples of OSHA standards include requirements for employers to:
provide fall protection such as a safety harness/line or guardrails; prevent
trenching cave-ins; prevent exposure to some infectious diseases; ensure the
safety of workers who enter confined spaces; prevent exposure to harmful
chemicals; put guards on dangerous machines; provide respirators or other
safety equipment; and provide training for certain dangerous jobs in a
language and vocabulary workers can understand.

Employers must also comply with the General Duty Clause of the OSH Act.
This clause requires employers to keep their workplaces free of serious
recognized hazards and is generally cited when no specific OSHA standard
applies to the hazard.

In its first year of operation, OSHA was permitted to adopt regulations based
on guidelines set by certain standards organizations, such as the American
Conference of Governmental Industrial Hygienists, without going through all
of the requirements of a typical rulemaking. OSHA is granted the authority to
promulgate standards that prescribe the methods employers are legally
required to follow to protect their workers from hazards. Before OSHA can
issue a standard, it must go through a very extensive and lengthy process
that includes substantial public engagement, notice and comment. The
agency must show that a significant risk to workers exists and that there are
feasible measures employers can take to protect their workers.

In 2000, OSHA issued an ergonomics standard. In March 2001, Congress

voted to repeal the standard through the Congressional Review Act. The
repeal, one of the first major pieces of legislation signed by President George
W. Bush, is the only instance that Congress has successfully used the
Congressional Review Act to block a regulation.

Since 2001, OSHA has issued the following standards:

2002: Exit Routes, Emergency Action Plans, and Fire Prevention Plans

2004: Commercial Diving Operations

2004: Fire Protection in Shipyards

2006: Occupational Exposure to Hexavalent Chromium

2006: Assigned Protection Factors for Respiratory Protection Equipment

2007: Electrical Installation Standard

2007: Personal Protective Equipment Payment (Clarification)

2008: Vertical Tandem Lifts

2010: Cranes and Derricks in Construction

2010: General Working Conditions in Shipyards

2012: GHS Update to the Hazard Communication Standard

2014: New Recordkeeping and Reporting Requirements for Employers

Enforcement[edit]
OSHA is responsible for enforcing its standards on regulated entities.
Compliance Safety and Health Officers carry out inspections and assess fines
for regulatory violations. Inspections are planned for worksites in particularly
hazardous industries. Inspections can also be triggered by a workplace
fatality, multiple hospitalizations, worker complaints, or referrals.

OSHA is a small agency, given the size of its mission: with its state partners,
OSHA has approximately 2,400 inspectors covering more than 8 million
workplaces where 130 million workers are employed. In Fiscal Year 2012
(ending Sept. 30), OSHA and its state partners conducted more than 83,000
inspections of workplaces across the United States just a fraction of the
nations worksites.[19] According to a report by AFLCIO, it would take OSHA
129 years to inspect all workplaces under its jurisdiction.[20]

Enforcement plays an important part in OSHAs efforts to reduce workplace

injuries, illnesses, and fatalities. Inspections are initiated without advance
notice, conducted using on-site or telephone and facsimile investigations,
performed by trained compliance officers and scheduled based on the
following priorities [highest to lowest]: imminent danger; catastrophes
fatalities or hospitalizations; worker complaints and referrals; targeted
inspections particular hazards, high injury rates; and follow-up inspections.

Current workers or their representatives may file a complaint and ask OSHA
to inspect their workplace if they believe that there is a serious hazard or that
their employer is not following OSHA standards. Workers and their
representatives have the right to ask for an inspection without OSHA telling
their employer who filed the complaint. It is a violation of the OSH Act for an
employer to fire, demote, transfer or in any way discriminate against a
worker for filing a complaint or using other OSHA rights.

When an inspector finds violations of OSHA standards or serious hazards,

OSHA may issue citations and fines. A citation includes methods an employer
may use to fix a problem and the date by which the corrective actions must
be completed. OSHAs fines are very low compared with other government
agencies. The maximum OSHA fine for a serious violation is $7,000, and the
maximum fine for a repeat or willful violation is $70,000. In determining the
amount of the proposed penalty, OSHA must take into account the gravity of
the alleged violation and the employers size of the business, good faith and
history of previous violations. Employers have the right to contest any part of
the citation, including whether a violation actually exists.[21] Workers only
have the right to challenge the deadline by which a problem must be
resolved. Appeals of citations are heard by the independent Occupational
Safety and Health Review Commission (OSHRC).

OSHA carries out its enforcement activities through its 10 regional offices and
90 area offices.[19] OSHAs regional offices are located in Boston, New York
City, Philadelphia, Atlanta, Chicago, Dallas, Kansas City metropolitan area,
Denver, San Francisco, and Seattle.

Recordkeeping requirements[edit]
Tracking and investigating workplace injuries and illnesses play an important
role in preventing future injuries and illnesses. Under OSHAs Recordkeeping

regulation, certain covered employers in high hazard industries are required

to prepare and maintain records of serious occupational injuries and illnesses.
This information is important for employers, workers and OSHA in evaluating
the safety of a workplace, understanding industry hazards, and implementing
worker protections to reduce and eliminate hazards.

Employers with more than ten employees and whose establishments are not
classified as a partially exempt industry must record serious work-related
injuries and illnesses using OSHA Forms 300, 300A and 301. Recordkeeping
forms, requirements and exemption information are at OSHAs website.[22]

Whistleblower protection[edit]
OSHA enforces the whistleblower provisions of the Occupational Safety and
Health Act and 21 other statutes protecting workers who report violations of
various airline, commercial motor carrier, consumer product, environmental,
financial reform, food safety, health care reform, nuclear, pipeline, public
transportation agency, maritime and securities laws.[14] Over the years,
OSHA has been responsible for enforcing these laws that protect the rights of
workers to speak up without fear of retaliation, regardless of the relationship
of these laws to occupational safety and health matters.[14]

Compliance assistance[edit]
OSHA has developed several training, compliance assistance, and health and
safety recognition programs throughout its history.

The OSHA Training Institute, which trains government and private sector
health and safety personnel, began in 1972.[23] In 1978, the agency began a
grant making program, now called the Susan Harwood Training Grant
Program, to train workers and employers in identifying and reducing
workplace hazards.[23]

The Voluntary Protection Program (VPP) recognize employers and workers in

private industry and federal agencies who have implemented effective safety
and health management programs and maintain injury and illness rates
below the national average for their respective industries. In VPP,
management, labor, and OSHA work cooperatively and proactively to prevent

fatalities, injuries, and illnesses through a system focused on: hazard

prevention and control, worksite analysis, training, and management
commitment and worker involvement.[23]

OSHAs On-site Consultation Program[24] offers free and confidential advice

to small and medium-sized businesses in all states across the country, with
priority given to high-hazard worksites. Each year, responding to requests
from small employers looking to create or improve their safety and health
management programs, OSHAs On-site Consultation Program conducts over
29,000 visits to small business worksites covering over 1.5 million workers
across the nation. On-site consultation services are separate from
enforcement and do not result in penalties or citations. Consultants from
state agencies or universities work with employers to identify workplace
hazards, provide advice on compliance with OSHA standards, and assist in
establishing safety and health management programs.[24]

Under the consultation program, certain exemplary employers may request

participation in OSHAs Safety and Health Achievement Recognition Program
(SHARP). Eligibility for participation includes, but is not limited to, receiving a
full-service, comprehensive consultation visit, correcting all identified hazards
and developing an effective safety and health management program.
Worksites that receive SHARP recognition are exempt from programmed
inspections during the period that the SHARP certification is valid.[25]

OSHA also provides compliance assistance through its national and area
offices. Through hundreds of publications in a variety of languages, website
safety and health topics pages, and through compliance assistance staff
OSHA provides information to employers and workers on specific hazards and
OSHA rights and responsibilities.[26]

Controversy[edit]
Much of the debate about OSHA regulations and enforcement policies
revolves around the cost of regulations and enforcement, versus the actual
benefit in reduced worker injury, illness and death. A 1995 study of several
OSHA standards by the Office of Technology Assessment (OTA) found that
OSHA relies "generally on methods that provide a credible basis for the
determinations essential to rulemakings". Though it found that OSHA's
finding and estimates are "subject to vigorous review and challenge", it

stated that that this is natural because "interested parties and experts
involved in rulemakings have differing visions".[27]

OSHA has come under considerable criticism for the ineffectiveness of its
penalties, particularly its criminal penalties. The maximum penalty is a
misdemeanor with a maximum of 6-months in jail.[28][dubious discuss] In
response to the criticism, OSHA, in conjunction with the Department of
Justice, has pursued several high-profile criminal prosecutions for violations
under the Act, and has announced a joint enforcement initiative between
OSHA and the United States Environmental Protection Agency (EPA) which
has the ability to issue much higher fines than OSHA. Meanwhile,
Congressional Democrats, labor unions and community safety and health
advocates are attempting to revise the OSH Act to make it a felony with much
higher penalties to commit a willful violation that results in the death of a
worker. Some local prosecutors are charging company executives with
manslaughter and other felonies when criminal negligence leads to the death
of a worker[citation needed].

During its more than 40 years of existence, OSHA has secured only 12
criminal convictions.[when?][29]

OSHA has been accused of being more devoted to the numbers of inspections
than to actual safety.[citation needed] Industry associations and unions have
resorted to court action to force OSHA to promulgate new standards such as
the hexavalent chromium standard. OSHA has also been criticized for taking
decades to develop new regulations.[citation needed] Speaking about OSHA
under the George W. Bush presidency on the specific issue of combustible
dust explosions, Chemical Safety Board appointee Carolyn Merritt said:[30]

The basic disappointment has been this attitude of no new regulation. They
don't want industry to be pestered. In some instances, industry has to be
pestered in order to comply.
------------------Good manufacturing practice
From Wikipedia, the free encyclopedia
Good manufacturing practices (GMP) are the practices required in order to

conform to the guidelines recommended by agencies that control

authorization and licensing for manufacture and sale of food, drug products,
and active pharmaceutical products. These guidelines provide minimum
requirements that a pharmaceutical or a food product manufacturer must
meet to assure that the products are of high quality and do not pose any risk
to the consumer or public.

Good manufacturing practices, along with good agricultural practices, good

laboratory practices and good clinical practices, are overseen by regulatory
agencies in the United States, Canada, Europe, China, and other countries.

Contents [hide]
1

High-level details

Guideline versions

Enforcement

Other good practices

See also

References

Sources

External links

High-level details[edit]
Good manufacturing practice guidelines provide guidance for manufacturing,
testing, and quality assurance in order to ensure that a food or drug product
is safe for human consumption. Many countries have legislated that food and
pharmaceutical and medical device manufacturers follow GMP procedures
and create their own GMP guidelines that correspond with their legislation.

All guidelines follow a few basic principles:

Manufacturing facilities must maintain a clean and hygienic manufacturing

area.

Controlled environmental conditions in order to prevent cross contamination

of food or drug product from adulterants that may render the product unsafe
for human consumption.
Manufacturing processes are clearly defined and controlled. All critical
processes are validated to ensure consistency and compliance with
specifications.
Manufacturing processes are controlled, and any changes to the process are
evaluated. Changes that affect the quality of the drug are validated as
necessary.
Instructions and procedures are written in clear and unambiguous language.
(Good Documentation Practices)
Operators are trained to carry out and document procedures.
Cross contamination with unlabelled major allergens is prevented.
Records are made, manually or by instruments, during manufacture that
demonstrate that all the steps required by the defined procedures and
instructions were in fact taken and that the quantity and quality of the food or
drug was as expected. Deviations are investigated and documented.
Records of manufacture (including distribution) that enable the complete
history of a batch to be traced are retained in a comprehensible and
accessible form.
The distribution of the food or drugs minimizes any risk to their quality.
A system is available for recalling any batch from sale or supply.
Complaints about marketed products are examined, the causes of quality
defects are investigated, and appropriate measures are taken with respect to
the defective products and to prevent recurrence.
Practices are recommended with the goal of safeguarding the health of
consumers and patients as well as producing good quality food, medicine,
medical devices, or active pharmaceutical products. In the United States, a
food or drug may be deemed "adulterated" if it has passed all of the
specifications tests, but is found to be manufactured in a facility or condition
which violates or does not comply with current good manufacturing guideline.
Therefore, complying with GMP is mandatory in all pharmaceutical
manufacturing, and most food processing.

GMP guidelines are not prescriptive instructions on how to manufacture

products. They are a series of general principles that must be observed

during manufacturing. When a company is setting up its quality program and
manufacturing process, there may be many ways it can fulfil GMP
requirements. It is the company's responsibility to determine the most
effective and efficient quality process.

The quality is built into the product and GMP is the most essential part of
ensuring this product quality.

Guideline versions[edit]
GMPs are enforced in the United States by the U.S. Food and Drug
Administration (FDA), under Title 21 CFR. The regulations use the phrase
"current good manufacturing practices" (cGMP) to describe these guidelines.
Courts may theoretically hold that a product is adulterated even if there is no
specific regulatory requirement that was violated as long as the process was
not performed according to industry standards.[citation needed] Since June
2010, a different set of cGMP requirements have applied to all manufacturers
of dietary supplements.[1]

The World Health Organization (WHO) version of GMP is used by

pharmaceutical regulators and the pharmaceutical industry in over one
hundred countries worldwide, primarily in the developing world. The
European Union's GMP (EU-GMP) enforces similar requirements to WHO GMP,
as does the FDA's version in the US. Similar GMPs are used in other countries,
with Australia, Canada, Japan, Saudi Arabia, Singapore, Philippines, Vietnam
and others having highly developed/sophisticated GMP requirements. In the
United Kingdom, the Medicines Act (1968) covers most aspects of GMP in
what is commonly referred to as "The Orange Guide", which is named so
because of the color of its cover; it is officially known as Rules and Guidance
for Pharmaceutical Manufacturers and Distributors.[2]

Since the 1999 publication of GMPs for Active Pharmaceutical Ingredients, by

the International Conference on Harmonization (ICH), GMPs now apply in
those countries and trade groupings that are signatories to ICH (the EU, Japan
and the U.S.), and applies in other countries (e.g., Australia, Canada,
Singapore) which adopt ICH guidelines for the manufacture and testing of
active raw materials.

GMC is part of quality assurance which ensures that products are consistently
produced and controlled to the quality standards appropriate to their
intended use and as required by marketing authorization or product
specification.

Enforcement[edit]
Within the European Union, GMP inspections are performed by National
Regulatory Agencies (e.g., GMP inspections are performed in the United
Kingdom by the Medicines and Healthcare Products Regulatory Agency
(MHRA)); in the Republic of Korea (South Korea) by the Ministry of Food and
Drug Safety (KFDA); in Australia by the Therapeutic Goods Administration
(TGA); in Bangladesh by the Directorate General of Drug Administration
(DGDA); in South Africa by the Medicines Control Council (MCC); in Brazil by
the National Health Surveillance Agency (ANVISA); in India GMP inspections
are carried out by state Food and Drugs Administrations (FDA) and these FDA
report to the Central Drugs Standard Control Organization; in Pakistan by the
Drug Regulatory Authority of Pakistan; in Nigeria by NAFDAC; and by similar
national organisations worldwide. Each of the inspectorates carry out routine
GMP inspections to ensure that drug products are produced safely and
correctly; additionally, many countries perform pre-approval inspections (PAI)
for GMP compliance prior to the approval of a new drug for marketing.

Regulatory agencies (including the FDA in the U.S. and regulatory agencies in
many European nations) are authorized to conduct unannounced inspections,
though some are scheduled. FDA routine domestic inspections are usually
unannounced, but must be conducted according to 704(a) of the FD&C Act
(21 USCS 374), which requires that they are performed at a "reasonable
time". Courts have held that any time the firm is open for business is a
reasonable time for an inspection.

Other good practices[edit]

Other good-practice systems, along the same lines as GMP, exist:

Good agricultural practice (GAP), for farming and ranching

Good laboratory practice (GLP), for laboratories conducting non-clinical

studies (toxicology and pharmacology studies in animals)

Good clinical practice (GCP), for hospitals and clinicians conducting clinical
studies on new drugs in humans
Good regulatory practice (GRP), for the management of regulatory
commitments, procedures and documentation
Good distribution practice (GDP) deals with the guidelines for the proper
distribution of medicinal products for human use
Good transportation practice (GTP) deals with the guidelines for the proper
domestic and international transportation of medicinal products for human
use
Good pharmacovigilance practice (GVP) deals with the safety of produced
drugs.
Collectively, these and other good-practice requirements are referred to as
"GxP" requirements, all of which follow similar philosophies. (Other examples
include good agriculture practices, good guidance practices, and good tissue
practices.) In the U.S., medical device manufacturers must follow what are
called "quality system regulations" which are deliberately harmonized with
ISO requirements, not cGMPs.
-------------------Corrective and preventive action
From Wikipedia, the free encyclopedia
Corrective and preventive action (CAPA, also called corrective action /
preventive action, or simply corrective action) are improvements to an
organization's processes taken to eliminate causes of non-conformities or
other undesirable situations.[1] CAPA is a concept within good manufacturing
practice (GMP), Hazard Analysis and Critical Control Points/Hazard Analysis
and Risk-based Preventive Controls (HACCP/HARPC) and numerous ISO
business standards. It focuses on the systematic investigation of the root
causes of identified problems or identified risks in an attempt to prevent their
recurrence (for corrective action) or to prevent occurrence (for preventive
action).

Corrective actions are implemented in response to customer complaints,

unacceptable levels of product non-conformance, issues identified during an
internal audit, or adverse or unstable trends in product and process
monitoring such as would be identified by statistical process control (SPC).

Preventive actions are implemented in response to the identification of

potential sources of non-conformity.

To ensure that corrective and preventive actions are effective, the systematic
investigation of the root causes of failure is pivotal. CAPA is part of the overall
quality management system (QMS).

Contents [hide]
1

Concepts

Medical devices and FDA compliance

Examples of corrective actions

See also

References

External links

Concepts[edit]
Clearly identified sources of data which identify problems that will be
investigated.
Root cause analysis to identify the cause of a discrepancy or deviation and
suggest corrective actions of a problem which is identified.
A common misconception is that the purpose of preventive action is to avert
the occurrence of a similar potential problem. This process is all part of
corrective action, because it is a process of determining such similarities that
should take place in the event of a discrepancy.

The PDCA cycle[2]

Preventive action is any proactive methodology used to determine potential
discrepancies before they occur and to ensure that they do not happen
(thereby including, for example, preventive maintenance, management
review or other common forms of risk avoidance). Corrective and preventive
actions both include investigation, action, review, and further action if so

required. It can be seen that both fit into the PDCA (plan-do-check-act)
philosophy as determined by the Deming-Shewhart cycle.

Investigations to root cause may conclude that no corrective or preventive

actions are required, and additionally may suggest simple corrections to a
problem with no identified systemic root cause. When multiple investigations
end in no corrective action, a new problem statement with expanded scope
may be generated, and a more thorough investigation to root cause
performed.

Implementation of corrective and preventive actions is the path towards

improvement and effectiveness of Quality Management Systems. Corrective
actions is nothing but the action/s based on the problem identification. The
problem or a non-conformance can be identified internally through staff
suggestions, management reviews, document reviews or internal audits.
Customer complaints / suggestions, customer rejections, non-conformities
raised in customer / third party audits and recommendations by the auditors
are the external sources which lead to find the root cause of the problem.

Root cause is the identification of the source of the problem where the
person(s), system, process or external factor is identified as the cause of the
non conformity.

Corrective action is the re-work / rectification activity of the non conforming

products as per ISO 9001:2008 (8.5.2).

Preventive action is prediction of problem and trying to avoid the occurrence

(fail safe) through self initiated actions and analysis related with
processes/products. This can be initiated with the help of active participation
of staff members/workers through improvement teams, improvement
meetings, opportunities for improvement during internal audits, management
review, customer feedback and deciding own goals quantized in terms of
business growth, reducing rejections, utilizing the equipment effectively, etc.

Medical devices and FDA compliance[edit]

In order to comply with FDA 21 CFR 820.100[3] medical device companies

need to establish a CAPA process within their QMS. This part of the system
may be paper or digital, but it is something that is looked for during an FDA
visit.[4] In 2015 there were over 450 issues found with the CAPA systems for
medical device companies. To have an FDA-compliant QMS system required
the ability to capture, review, approve, control, and retrieve closed-loop
processes.[5]

Examples of corrective actions[edit]

Error Proofing
Visible or Audible Alarms
Process Redesign
Product Redesign
Training or enhancement/ modification of existing training programmes
Improvements to maintenance schedules
Improvements to material handling or storage
In some cases a combination of such actions may be necessary to fully
correct the problem.
----------------Question
notebook).

Instructions/questions (note any exceptions and comments in

Yes, No, or NA

1.0

General Controls

Does the facility and its departments (organizational units) operate in a

state of control as defined by the GMP regulations?
Is there documented proof to substantiate the finding?

GMPs for the Food Industry (21 CFR Part 110)? Yes ___

No ___

GMPs for the Dietary Supplements Industry (21 CFR Part 111)? Yes ___
___
GMPs for the Drug Industry (21 CFR Part 210/211)? Yes ___

No ___

GMPs for the Medical Device Industry (21 CFR Part 820)? Yes ___
GMPs for Active Pharmaceutical Ingredients (ICH Q7)? Yes ___

1.1

No

No ___

No ___

Organizational & Management Responsibilities

1.101 Does this facility/business unit operate under a facility or corporate

quality policy?
Is there a formal corporate quality manual (ICH Q10)?
1.102 211.22(a) Does a Quality Assurance unit (department) exist as a
separate organizational entity?
Is there proof that no conflict of interest exists within the organization?
Where does the QA unit position itself on the organizational chart?
1.103 211.22(a) Does the Quality Assurance unit alone have both the
authority and responsibility to approve or reject all components, drug product
containers and closures, in-process materials, packaging materials, labeling
and drug products?
Is the authority and responsibility supported by corporate management?
1.104 211.22 Does the QA department or unit routinely review production
records to ensure that procedures were followed and properly documented?
1.105 211.22(b) Are adequate laboratory space, equipment, and qualified
personnel available to perform testing and operations at the Auditee's
facilities?
1.106 If any portion of testing is performed by a contractor, has the Quality
Assurance unit inspected the contractors site and verified that the laboratory
space, equipment, qualified personnel and procedures are adequate?
Has those facilities undergone appropriate risk assessments and auditing if
applicable?

1.107 Is there a formal documented calendar plan for inspections available

for review?
Is there a documented list of previous inspection dates?
Date of last inspection:____________________
1.108 211.22(c) Are all QA procedures in writing?
1.109 211.22(c) Are all QA responsibilities in writing?
1.110 Are all written QA procedures current and approved? (Review log of
procedures)
1.111 Are the procedures followed? (Examine records to ensure consistent
record-keeping that adequately documents testing.)
1.112 211.25 Are QA supervisory personnel qualified by way of training and
experience?
1.113 211.25 Are other QA personnel, e.g., chemists, analysts, laboratory
technicians) qualified by way of training and experience?
1.2

Document Control Program

1.201 211.22(a) Does the QA unit have a person or department specifically

charged with the responsibility of designing, revising, and obtaining approval
for production and testing procedures, forms, and records?
1.202 211.22(d) Does a written SOP, which identifies how the form is to be
completed and who signs and countersigns, exist for each record or form?
1.203 211.165(a)(b)(c) Is the production batch record and release test
results reviewed for accuracy and completeness before a batch/lot of finished
product is released?
1.3

Employee Orientation, Quality Awareness, and Job Training

1.301 Circle the types of orientation provided to each new employee: (1)
Company brochure (2) Literature describing GMP regulations and stressing
importance of following instructions. (3) On-the-job training for each function
to be performed (before the employee is allowed to perform such tasks). (4)
Other: enter in notebook.
1.302 211.25(a) Does each employee receive retraining on an SOP
(procedures) if critical changes have been made in the procedure?
1.303 Indicate how on-going, periodic GMP training is accomplished.

1.304 211.25 is all training documented in writing that indicates the date of
the training, the type of training, and the signature of both the employee and
the trainer?
1.305 211.25 Are training records readily retrievable in a manner that
enables one to determine what training an employee has received, which
employees have been trained on a particular procedure, or have attended a
particular training program?
1.306 Are GMP trainers qualified through experience and training?
1.307 211.25(a) Are supervisory personnel instructed to prohibit any
employee who, because of any physical condition (as determined by medical
examination or supervisory observation) that may adversely affect the safety
or quality of drug products, from coming into direct contact with any drug
component or immediate containers for finished product?
1.308 211.28(d) Are employees required to report to supervisory personnel
any health or physical condition that may have an adverse effect on drug
product safety and purity?
1.309 211.25(a) Are temporary employees given the same orientation as
permanent employees?
1.310 211.34 Are consultants, who are hired to advise on any aspect of
manufacture, processing, packing or holding, of approval for release of drug
products, asked to provide evidence of their education, training, and
experience?
1.311 211.34 Are written records maintained stating the name, address,
qualifications, and date of service for any consultants and the type of service
they provide?
1.4

Plant Safety and Security

1.401 Does this facility have a facility or corporate safety program?

1.402 Are safety procedures written?
1.403 Are safety procedures current?
1.404 Do employees receive safety orientation before working in the plant
area?
1.405 Is safety training documented in a readily retrievable manner that
states the name of the employee, the type of training, the date of the
training, and the name of the trainer and the signature of the trainer and the
participant?

1.406 Does this facility have a formal, written security policy?

1.407 Is access to the facility restricted?
1.408 Describe how entry is monitored/restricted:
1.409 Is a security person available 24 hours per day?
1.5

Internal Quality/GMP Audit Program

1.501 Does this business unit/facility have a written quality policy?

1.502 Is a copy of this quality policy furnished to all employees?
1.503 If "yes" to above, when provided? __________________
1.504 Is training provided in quality improvement?
1.505 Does a formal auditing function exist in the Quality Assurance
department?
1.506 Does a written SOP specify who shall conduct audits and qualifications
(education, training, and experience) for those who conduct audits?
1.507 Does a written SOP specify the scope and frequency of audits and how
such audits are to be documented?
1.508 Does a written SOP specify the distribution of the audit report?
1.6

Quality Cost Program

1.601 Does this facility have a periodic and formal review of the cost of
quality?
1.602 Does this facility have the ability, through personnel, software, and
accounting records, to identify and capture quality costs?
1.603 Does this facility make a conscious effort to reduce quality costs?
2.0

Design Control

Not directly related to the Drug Regulation

3.0

Facility Control

3.1

Facility Design and Layout

3.101 211.42(a) Are all parts of the facility constructed in a way that makes
them suitable for the manufacture, testing, and holding of drug products?
3.102 211.42(b) Is there sufficient space in the facility for the type of work
and typical volume of production?
3.103 Does the layout and organization of the facility prevent contamination?
3.2

Environmental Control Program

3.201 The facility is NOT situated in a location that potentially subjects

workers or product to particulate matter, fumes, or infestations?
3.202 Are grounds free of standing water?
3.203 211.44 Is lighting adequate in all areas?
3.204 211.46 Is adequate ventilation provided?
3.205 211.46 Is control of air pressure, dust, humidity and temperature
adequate for the manufacture, processing, storage or testing of drug
products?
3.206 211.46 If air filters are used, is there a written procedure specifying
the frequency of inspection and replacement?
3.207 Are drains and routine cleaning procedures sufficient to prevent
standing water inside the facility?
3.208 211.42(d) Does the facility have separate air handling systems, if
required, to prevent contamination? (MANDATORY IF PENICILLIN IS PRESENT!)
3.3

Facility Maintenance and Good Housekeeping Program

3.301 211.56(a) Is this facility free from infestation by rodents, birds, insects
and vermin?

3.302 211.56(c) Does this facility have written procedures for the safe use of
suitable, (e.g. those that are properly registered) rodenticides, insecticides,
fungicides, and fumigating agents?
3.303 Is this facility maintained in a clean and sanitary condition?
3.304 Does this facility have written procedures that describe in sufficient
detail the cleaning schedule, methods, equipment and material?
3.305 Does this facility have written procedures for the safe and correct use
of cleaning and sanitizing agents?
3.306 211.58 Are all parts of the facility maintained in a good state of
repair?
3.307 211.52 Is sewage, trash and other refuse disposed of in a safe and
sanitary manner (and with sufficient frequency?)
3.4

Outside Contractor Control Program

3.401 211.56(d) Are contractors and temporary employees required to

perform their work under sanitary conditions?
3.402 Are contractors qualified by experience or training to perform tasks
that may influence the production, packaging, or holding of drug products?
4.0

Equipment Control

4.1

Equipment Design and Placement

4.101 211.63 Is all equipment used to manufacture, process or hold a drug

product of appropriate design and size for its intended use?
4.102 Are the following pieces of equipment suitable for their purpose?
Blender(s), Conveyor(s), Tablet, Presses, Capsule Fillers, Bottle Fillers, Other
(specify).
4.103 Are the following pieces of equipment suitable in their size/capacity?
Blender(s), Conveyor(s), Tablet, Presses, Capsule Fillers, Bottle Fillers, Other
(specify).

4.104 Are the following pieces of equipment suitable in their design?

Blender(s), Conveyor(s), Tablet, Presses, Capsule Fillers, Bottle Fillers, Other
(specify).
4.105 Are the locations in the facility of the following pieces of equipment
acceptable? Blender(s), Conveyor(s), Tablet, Presses, Capsule Fillers, Bottle
Fillers, Other (specify).
4.106 Are the following pieces of equipment properly installed? Blender(s),
Conveyor(s), Tablet, Presses, Capsule Fillers, Bottle Fillers, Other (specify).
4.107 Is there adequate space for the following pieces of equipment?
Blender(s), Conveyor(s), Tablet, Presses, Capsule Fillers, Bottle Fillers, Other
(specify).
4.108 211.65(a) Are machine surfaces that contact materials or finished
goods non-reactive, non-absorptive, and non-additive so as not to affect the
product?
4.109 211.65(b) Are design and operating precautions taken to ensure that
lubricants or coolants or other operating substances do NOT come into
contact with drug components or finished product?
4.110 211.72 Fiber-releasing filters are NOT used in the production of
injectable products?
4.111 211.72 Asbestos filters are NOT used in the production of products?
4.112 Is each idle piece of equipment clearly marked "needs cleaning" or
"cleaned; ready for service"?
4.113 Is equipment cleaned promptly after use?
4.114 Is idle equipment stored in a designated area?
4.115 211.67(a)(b) Are written procedures available for each piece of
equipment used in the manufacturing, processing or holding of components,
in-process material or finished product?
4.116 Do cleaning instructions include disassembly and drainage procedure,
if required, to ensure that no cleaning solution or rinse remains in the
equipment?
4.117 Does the cleaning procedure or startup procedure ensure that the
equipment is systematically and thoroughly cleaned?

4.2

Equipment Identification

4.201 211.105 Are all pieces of equipment clearly identified with easily
visible markings?
4.202 211.105(b) Are all pieces of equipment also marked with an
identification number that corresponds with an entry in an equipment log?
4.203 Does each piece of equipment have written instructions for
maintenance that includes a schedule for maintenance?
4.204 Is the maintenance log for each piece of equipment kept on or near the
equipment?
4.3

Equipment Maintenance & Cleaning

4.301 211.67(b) Are written procedures established for the cleaning and
maintenance of equipment and utensils?
4.302 Are these procedures followed?
4.303 211.67(b)(1) Does a written procedure assign responsibility for the
cleaning and maintenance of equipment?
4.304 211.67(b)(2) Has a written schedule been established and is it
followed for the maintenance and cleaning of equipment?
4.305 Has the cleaning procedure been properly validated?
4.306 211.67(b)(2) If appropriate, is the equipment sanitized using a
procedure written for this task?
4.307 211.67(b)(3) Has a sufficiently detailed cleaning and maintenance
procedure been written for each different piece of equipment to identify any
necessary disassembly and reassembly required to provide cleaning and
maintenance?
4.308 211.67(b)(3) Does the procedure specify the removal or obliteration of
production batch information from each piece of equipment during its
cleaning?
4.309 Is equipment cleaned promptly after use?
4.310 Is clean equipment clearly identified as "clean" with a cleaning date
shown on the equipment?
4.311 211.67(b)(5) Is clean equipment adequately protected against
contamination prior to use?

4.312 211.67(b) Is equipment inspected immediately prior to use?

4.313 211.67(c) Are written records maintained on equipment cleaning,
sanitizing and maintenance on or near each piece of equipment?
4.4

Measurement Equipment Calibration Program

4.401 211.68(a) Does the facility have approved written procedures for
checking and calibration of each piece of measurement equipment? (Verify
procedure and log for each piece of equipment and note exceptions in
notebook with cross reference.)
4.402 211.68(a) Are records of calibration checks and inspections
maintained in a readily retrievable manner?
4.5

Equipment Qualification Program

4.501 211.63 Verify that all pieces of equipment used in production,

packaging, and quality assurance are capable of producing valid results.
4.502 211.68(a) When computers are used to automate production or
quality testing, have the computer and software been validated?
4.503 Have on-site tests of successive production runs or tests been used to
qualify equipment?
4.504 Were tests repeated a sufficient number of times to ensure reliable
results?
4.505 211.63 Is each piece of equipment identified to its minimum and
maximum capacities and minimum and maximum operating speeds for valid
results?
4.506 Have performance characteristics been identified for each piece of
equipment? (May be provided by the manufacturer, but must be verified
under typical operations conditions.)
4.507 Have operating limits and tolerances for performance been established
from performance characteristics?
5.0

Material/Component Control

5.1

Material/Component Specification and Purchasing Control

Although purchasing is not specifically addressed in the current GMP

regulation, incumbent upon user of components and materials to ensure
quality of product, material or component.
5.101 Has each supplier/vendor of material or component been
inspected/audited for proper manufacturing controls? (Review suppliers and
audits and enter names, material supplied, and date last audited in
notebook.)
5.2
Material/Component Receipt, Inspection, Sampling, and Laboratory
Testing
5.201 211.80(a) Does the facility have current written procedures for
acceptance/rejections of drug products, containers, closures, labeling and
packaging materials? (List selected materials and components in notebook
and verify procedures.)
5.202 211.80(d) Is each lot within each shipment of material or components
assigned a distinctive code so material or component can be traced through
manufacturing and distribution?
5.203 211.82(a) Does inspection start with visual examination of each
shipping container for appropriate labeling, signs of damage, or
contamination?
5.204 211.82(b) Is the number of representative samples taken from a
container or lot based on statistical criteria and experience with each type of
material or component?
5.205 211.160(b) Is the sampling technique written and followed for each
type of sample collected?
5.206 Is the quantity of sample collected sufficient for analysis and reserve in
case retesting or verification is required?
Verify that the following steps are included in written procedures
unless more specific procedures are followed:
5.207 211.84(c)(2) Containers are cleaned before samples are removed.
5.208 211.84(c)(4) Stratified samples are not composited for analysis.

5.209 211.84(c)(5) Containers from which samples have been taken are so
marked indicating date and approximate amount taken.
5.210 Each sample container is clearly identified by material or component
name, lot number, date sample taken, name of person taking sample, and
original container identification.
5.211 211.84(d)(1)(2) At least one test is conducted to confirm the identity
of a raw material (bulk chemical or pharmaceutical) when a Certificate of
Analysis is provided by supplier and accepted by QA.
5.212 If a Certificate of Analysis is not accepted for a lot of material, then
additional testing is conducted by a written protocol to determine suitability
for purpose.
5.213 211.84(d)(6) Microbiological testing is conducted where appropriate.
5.3

Material Component Storage and Handling

(Verify that materials and components are stored and handled in a way
that prevents contamination, mixups, and errors.)
5.301 211.42(b) Are incoming material and components quarantined until
approved for use?
5.302 Are all materials handled in such a way to prevent contamination?
5.303 Are all materials stored off the floor?
5.304 Are materials spaced to allow for cleaning and inspection?
5.305 211.122(d) Are labels for different products, strengths, dosage forms,
etc., stored separately with suitable identification?
5.306 Is label storage area limited to authorized personnel?
5.307 211.89 Are rejected components, material, and containers
quarantined and clearly marked to prevent their use?
5.4

Inventory Control Program

5.401 211.142 Are inventory control procedures written?

5.402 Does the program identify destruction dates for obsolete or out-dated
materials, components, and packaging materials?
5.403 211.150(a) Is stock rotated to ensure that the oldest approved

product or material is used first?

5.404 211.184(e) Is destruction of materials documented in a way that
clearly identifies the material destroyed and the date on which destruction
took place?
5.5

Vendor (Supplier) Control Program

5.501 Are vendors periodically inspected according to a written procedure?

5.502 Is the procedure for confirming vendor test results written and
followed?
6.0

Operational Control

6.1

Material/Component/Label Verification, Storage, and Handling

6.101 211.87 Do written procedures identify storage time beyond which

components, containers, and closures must be reexamined before use?
6.102 211.87 Is release of retested material clearly identified for use?
6.103 Are retesting information supplements originally obtained?
6.104 Do written procedures identify steps in the dispensing of material for
production?
6.105 Do these procedures include (1) release by QC, (2)Documentation of
correct weight or measure, and (3) Proper identification of containers?
6.106 Does a second person observe weighing/measuring/dispensing and
verify accuracy with a second signature?
6.107 211.101(c) Is the addition of each component documented by the
person adding the material during manufacturing?
6.108 211.101(d) Does a second person observe each addition of material
and document verification with a second signature?
6.109 211.125(a) Does a written procedure specify who is authorized to
issue labels?

6.110 211.125(a) Does a written procedure specify how labels are issued,
used, reconciled with production, returned when unused, and the specific
steps for evaluation of any discrepancies?
6.111 211.125(d) Do written procedures call for destruction of excess
labeling on which lot or control numbers have been stamped or imprinted?
6.2

Equipment/Line/Area Cleaning, Preparation, and Clearance

6.201 211.67(b)(5) Do written procedures detail how equipment is to be

checked immediately prior to use for cleanliness, removal of any labels and
labeling from prior print operations?
6.202 211.67(b)(3) Do written procedures detail any disconnection and
reassembly required to verify readiness for use?
6.3

Operational Process Validation and Production Change Order Control

6.301 Have production procedures been validated? (Review selected

procedures for validation documentation. Adequate?)
6.302 211.100(a) Does the process control address all issues to ensure
identity, strength, quality and purity of product?
6.303 211.101(a) Does the procedure include formulation that is written to
yield not less than 100% of established amount of active ingredients?
6.304 211.101(c) Are all weighing and measuring preformed by one
qualified person and observed by a second person?
6.305 211.101(d) Have records indicated preceding policy been followed by
presence of two signatures?
6.306 211.103 Are actual yields calculated at the conclusion of appropriate
phases of the operation and at the end of the process?
6.307 211.103 Are calculations performed by one person? Is there
independent verification by a second person?
6.4

In-Process Inspection, Sampling, and Laboratory Control

6.401 211.110(a) Are written procedures established to monitor output and

validate the performance of manufacturing procedures that may cause
variability in characteristics of in-process materials and finished drug
products?
6.402 211.110(c) Are in-process materials tested at appropriate phases for

identity, strength, quality, purity and are they approved or rejected by Quality
Control?
6.403 211.160(b) Are there laboratory controls including sampling and
testing procedures to assure conformance of components, containers,
closures, in-process materials, and finished product specifications?
6.5

Reprocessing/Disposition of Materials

6.501 211.115(a) Do written procedures identify steps for reprocessing

batches?
6.502 211.115(b) Are quality control review and approval required for any
and all reprocessing of material?
6.503 Does testing confirm that reprocessed batches conform to established
specification?
6.504 Does a written procedure outline steps required to reprocess returned
drug products (if it can be determined that such products have not been
subjected to improper storage conditions?)
6.505 Does Quality Control review such reprocessed returned goods and test
such material for conformance to specifications before releasing such
material for resale?
7.0

Finished Product Control

7.1

Finished Product Verification, Storage, and Handling

7.101 211.30 Do written procedures indicate how and who verifies that
correct containers and packages are used for finished product during the
finishing operation?
7.102 211.134(a) In addition, do written procedures require that
representative sample of units be visually examined upon completion of
packaging to verify correct labeling?
7.103 211.137(a) Are expiration dates stamped or imprinted on labels?

7.104 211.137(b) Are expiration dates related to any storage conditions

stated on the label?
7.105 211.142(a) Are all finished products held in quarantine until QC has
completed its testing and releases product on a batch to batch basis for sale?
7.106 211.142(o) Is finished product stored under appropriate conditions of
temperature, humidity, light, etc.
7.2
Finished Product Inspection, Sampling, Testing, and Release for
Distribution
7.201 211.166 Has the formulation for each product been tested for stability
based on a written protocol? (Containers must duplicate those used in final
product packaging.)
7.202 211.166 Are written sampling and testing procedures and acceptance
criteria available for each product to ensure conformance to finished product
specifications?
7.203 211.170(a) Is a quantity of samples equal to at least twice the
quantity needed for finished product release testing maintained as a reserve
sample?
7.204 211.167(a) Are sterility and pyrogen testing performed as required?
7.205 211.167(b) Are specific tests for foreign particles or abrasives
included for any ophthalmic ointments?
7.206 211.167(c) Do controlled release or sustained release products
include tests to determine conformance to release time specification?
7.3

Distribution Controls

7.301 211.150(a) Does a written procedure manage stocks to ensure that

oldest approved product is sold first?
7.302 211.150(a) Are deviations to the policy above documented?
7.303 211.150(a) Does a written procedure identify the steps required if a
product recall is necessary?
7.304 Is the recall policy current and adequate?
7.4

Marketing Controls

7.401 The current regulation does not address marketing controls per se

except that all finished products must meet their specifications.

7.5

Complaint Handling and Customer Satisfaction Program

7.501 211.198(a) Are complaints, whether received in oral or written form,

documented in writing and retained in a designated file?
7.502 211.198(a) Are complaints reviewed on a timely basis by the Quality
Control Unit?
7.503 211.198(b)(1) Is the action taken in response to each complaint
documented?
7.504 211.198(b)(3) Are decisions not to investigate a complaint also
documented and the name of the responsible person documented?
7.505 211.198(b)(2) Are complaint investigations documented and do they
include investigation steps, findings, and follow-up steps, if required? Are
dates included for each entry?
------------------------------